DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 47-69, 71-74, 76-84 and 93-110 are pending in this application.
Applicant’s amendment to the claims filed 11/12/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification filed 11/12/2025 is acknowledged.
Applicant’s remarks filed on 11/12/2025 in response to the non-final rejection mailed on 08/11/2025 is acknowledged and has been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, corresponding to claims 47-65, drawn to the technical feature of a microorganism genetically modified for production of at least one glycosylated product, wherein the microorganism is a bacterium or yeast, and wherein the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway selected from the group consisting of cell wall carbohydrate antigen biosynthesis, capsular polysaccharide biosynthesis, cell wall protein mannosylation biosynthesis, beta-1,3-glucan biosynthesis, beta- 1,6-glucan biosynthesis and/or chitin biosynthesis when the microorganism is a yeast, mycolic acid and/or arabinogalactan biosynthesis when the microorganism is a Corynebacterium, Nocardia, or Mycobacterium, and teichoic acid biosynthesis when the microorganism is a Gram-positive bacterium,
Species A1) cell wall carbohydrate antigen biosynthesis,
Species B2) putative glycosyltransferase,
Species C2) WbbK (optionally given by SEQ ID NO: 28), or a polypeptide sequence having 80% or more sequence identity to the full-length sequence of SEQ ID NO: 28 and having glycosyltransferase activity,
Species D1) UDP-N-acetylglucosamine-undecaprenyl-phosphate N-acetylglucosaminephosphotransferase,
Species E1) rfe (optionally as given by SEQ ID NO: 15), or a polypeptide sequence having 80% or more sequence identity to the full-length sequence of SEQ ID NO: 15 and having UDP-N-acetylglucosamine-undecaprenyl-phosphate N-acetylglucosaminephosphotransferase activity
Species F1) putative colanic acid biosynthesis protein, and
Species G1) WcaM (optionally as given by SEQ ID NO: 39), or a polypeptide sequence having 80% or more sequence identity to the full-length sequence of SEQ ID NO: 39 and having colanic acid biosynthesis protein activity,
elected without traverse in the reply filed 06/16/2025.
Claims 66-69, 71-74, 76-84 and 93-110 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/16/2025.
Claims 55-58 and 61-63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/16/2025.
Claims 47-54, 59-60 and 64-65 are being examined on the merits only to the extent they read on the elected subject matter.
Objections to Specification
The objections to the specification regarding the use of trademarks and embedded hyperlinks are withdrawn in view of the amendments to remove embedded hyperlinks and to address the use of trademarks.
The disclosure is objected to because of the following informalities.
The Sequence Listing must be referenced by a statement in the specification identifying (i) the name of the file; (ii) the date of creation; and (iii) the size of the file in bytes (MPEP 1.823.b.1), however the specification filed 11/12/2025 lists the size of the file in kilobytes.
Appropriate correction is required.
Claim Objections
The objections to the claims are withdrawn in view of
The amendment to claim 47 to recite “wherein the biosynthesis of the cell wall … is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway” and “wherein the cell wall biosynthesis pathway is … selected from”,
the amendment to claim 54 to recite “wherein the biosynthesis of the cell wall … is additionally reduced by a deletion of at least one enzyme within a further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a further cell wall biosynthesis pathway”, and
the amendment to claims 59-60 to recite “provided by a deletion, or by reduced or abolished expression of at least one”.
Claim 47 is objected to for the phrase “wherein the biosynthesis of the cell wall of the microorganism that is reduced … compared to a microorganism” in lines 4-7. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the biosynthesis of the cell wall of the microorganism
Claim Rejections - 35 USC § 112(b)
The rejection of claims 47-54, 59-60 and 64-65 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention are withdrawn in view of the instant amendments to the claims.
Claims 47-54, 59-60 and 64-65 are newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The instant rejection is necessitated by claim amendment.
Claim 47 recites the phrase “the biosynthesis of the cell in the microorganism” in lines 7-8. There is insufficient antecedent basis for this limitation in the claim.
Claim 47 (claims 48-54, 59-60 and 64-65 dependent therefrom) is indefinite for the phrase “wherein the biosynthesis of the cell wall of the microorganism that is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell in the microorganism has not been reduced” in lines 4-8. As written, the claim requires the comparison of a first cell with reduced activity to a second cell lacking a different reduced activity to determine if the first cell has reduced activity. Put another way, the claimed “deletion of at least one enzyme within a cell wall biosynthesis pathway or reduction or abolished expression of at least one enzyme within a cell wall biosynthesis pathway” is not required to be compared to a microorganism lacking a deletion of the same at least one enzyme, or lacking the reduced or abolished expression of the same at least one enzyme. Therefore the reference for comparison is insufficient for one of ordinary skill in the art to determine the recited level of activity in the claims.
Applicant should consider an amendment to recite “wherein the biosynthesis of the cell wall of the microorganism is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism lacking the deletion of the at least one enzyme within the cell wall biosynthesis pathway; or is reduced by a reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism lacking the reduced or abolished expression of the at least one enzyme within the cell wall biosynthesis pathway”.
Claims 47 (claims 48-54, 59-60 and 64-65 dependent therefrom) and 54 (claims 59-60 dependent therefrom) are indefinite for the phrase “a deletion of at least one enzyme within a cell”. The term “deletion” is not specifically defined in the instant specification, and therefore it is unclear how one of skill in the art would delete an enzyme, as the process of “deletion” in the art involves genes or nucleotides rather than enzymes or proteins.
Claim 54 (claims 59-60 dependent therefrom) is indefinite for the phrase “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion of at least one enzyme in a further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a further cell wall biosynthesis pathway, compared to a bacterium lacking deletion of at least one enzyme within the further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within the further cell wall synthesis pathway”. The claim is being interpreted that the comparison is being made to a bacterium either lacking deletion of at least one enzyme within the further cell wall synthesis pathway, or lacking reduced or abolished expression of at least one enzyme within the further cell wall synthesis pathway. In view of this interpretation, the determination of the reduced cell wall biosynthesis activity required by the claim encompasses the comparison of a bacterium with reduced expression of at least one enzyme to a bacterium lacking deletion of at least one enzyme. Additionally, the claimed deletion of at least one enzyme in a further cell wall biosynthesis pathway or reduction or abolished expression of at least one enzyme in a further cell wall biosynthesis pathway is not required to be compared to a microorganism lacking a deletion of the same at least one enzyme, or lacking the reduced or abolished expression of the same at least one enzyme. Therefore the reference for comparison is insufficient for one of ordinary skill in the art to determine the recited level of activity in the claims.
Applicant should consider an amendment to recite “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion of at least one enzyme in a further cell wall biosynthesis pathway compared to a bacterium lacking the deletion of the at least one enzyme within the further cell wall biosynthesis pathway; or is additionally reduced by a reduced or abolished expression of at least one enzyme within the further cell wall synthesis pathway compared to a bacterium lacking the reduced or abolished expression of the at least one enzyme within the further cell wall synthesis pathway”.
Claim 59 (claim 60 dependent therefrom) recites the limitation “the colanic acid biosynthesis gene cluster” in line 6. There is insufficient antecedent basis for this limitation in the claims.
Claim 59 (claim 60 dependent therefrom) is indefinite for the phrase “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a reduced biosynthesis of colanic acid compared to a bacterium wherein the biosynthesis has not been reduced, wherein the reduced biosynthesis of colanic acid is provided by a deletion, or by reduced or abolished expression of at least one of the genes present in the colanic acid biosynthesis gene cluster”. As written, the claim requires the comparison of a first bacterium with reduced biosynthesis activity to a second bacterium without reduced activity to determine if the first bacterium has reduced activity. Put another way, the activity of the claimed bacterium with a deletion, or with a reduced or abolished expression of at least one of the genes present in the colanic acid biosynthesis gene cluster, is not required to be compared to a microorganism lacking the same deletion, or lacking the reduced or abolished expression of the at least one of the genes present in the colanic acid biosynthesis gene cluster. Additionally, it is unclear whether the “the biosynthesis” in the phrase “compared to a bacterium wherein the biosynthesis has not been reduced” in line 4 is referring to the biosynthesis of colanic acid, or the biosynthesis of the well wall of the bacterium that are both recited previously in the claim. Therefore the reference for comparison is insufficient for one of ordinary skill in the art to determine the recited level of activity in the claims.
Applicant should consider an amendment to recite “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion of at least one of the genes present in a colanic acid biosynthesis gene cluster compared to a bacterium lacking the deletion of at the least one of the genes present in the colanic acid biosynthesis gene cluster, or is reduced by a reduced or abolished expression of at least one of the genes present in the colanic acid biosynthesis gene cluster compared to a bacterium lacking the reduced or abolished expression of the at least one of the genes present in the colanic acid biosynthesis gene cluster”.
Response to Remarks: beginning on page 17 of Applicant’s response to rejections under 35 USC 112(b); Applicant in summary contends the amended claims overcome the rejections of record.
Applicant’s remarks are considered and found not convincing, as the amendments to the claims have necessitated new grounds of rejection, and the amendment to claim 59 does not provide antecedent basis for the limitation “the colanic acid biosynthesis gene cluster” as previously set forth.
Claim Rejections - 35 USC § 112(a)
Claim Interpretation: The claims are drawn to a microorganism genetically modified for production of at least one glycosylated product, wherein the microorganism is a bacterium or yeast, and wherein the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway, which cell wall biosynthesis pathway is at least one pathway selected from the group consisting of: cell wall carbohydrate antigen biosynthesis, O-antigen biosynthesis or common-antigen biosynthesis when the microorganism is a Gram-negative bacterium, capsular polysaccharide biosynthesis, cell wall protein mannosylation biosynthesis, beta-1,3-glucan biosynthesis, beta-1,6-glucan biosynthesis and/or chitin biosynthesis when the microorganism is a yeast, mycolic acid and/or arabinogalactan biosynthesis when the microorganism is a Corynebacterium, Nocardia, or Mycobacterium, and teichoic acid biosynthesis when the microorganism is a Gram-positive bacterium.
As the reduction, reduced or abolished expression of at least one enzyme within the cell wall biosynthesis pathway does not recite any structural change to any specific gene in the recited pathways, the genetic modifications are considered to be structurally unlimited. Additionally, as the recited change in gene expression is not correlated to the function of producing of a glycosylated product, the genetic modifications are considered to be functionally unlimited. Therefore, the claimed reduction, reduced or abolished expression of at least one enzyme represents a genus of genetic modifications that are considered to be widely variant with respect to both structure and function.
Claims 47-54, 59-60 and 64-65 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
MPEP § 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163.II.A.3.(a).ii) states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
According to § MPEP 2163.II.A.3.(a).ii), “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’”
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. According to MPEP § 2163, “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient."
The claims recite (in relevant part) a microorganism comprising a genus of genetic modifications to a cell wall biosynthesis pathway that causes reduced activity in cell wall biosynthesis. As stated above, the genus of genetic modifications is structurally unlimited in terms of which genes are being modified, and how these genes are being modified, as well as functionally unlimited in terms of the correlation between the genetic modifications and the function of producing a glycosylated product. In this case, the genus of genetic modifications encompasses species that are considered to be widely variant with respect to both structure and function.
The specification discloses the following representative microorganisms containing species of the genus of recited genetic modifications:
E. coli bearing gene knock-out mutations of lacZ, lacY, lacA, glgC, agp, pfkA, pfkB, pgi, arcA, iclR, wcaJ, pgi, lon and thyA, knock-in mutations of lacY, frk, and SP, and expression of alpha-1,2- and alpha-1,3-fucosyltransferase,
E. coli bearing gene knock-out mutations of lacZ and nagB, and knock-in mutations of lgtA, wgbO, lgtB,
E. coli bearing gene knock-out mutations of lacZ, nagABCDE, nanA, nanE, nanK, manXYZ, and knock-in mutations of glmS, GNA1, BoAGE, NeuB, NeuA, and a beta-galactosidase,
B. subtilis bearing lacY, and gene knock-out mutations nagA, nagB and gamA along with:
knock-in mutations of alpha-1,2- and alpha-1,3-fucosyltransferase, or
knock-in mutations of lgtA, wbgO, lgtB, and
overexpression of BsglmS, ScGNA1, BoAGE, CjneuB, NMneuA, PdbST, or NmST,
C. glutamicum bearing lacY, and expression of alpha-1,2- and/or alpha-1,3-fucosyltransferase expression, lgtA, wbgO, lgtB, CgglmS, ScGNA1, BoAGE and CjneuB, as well as knock-outs of nagA, nagB and gamA,
E. coli with deletions of all or of a selection of the genes:
rfe, wzzE, wecB, wecC, rffG, rffH, rffC, wecE, wzxE, wecF, wzyE or rffM,
wbbK, wbbJ, wbbI, wbbH, glf, rfbX, tfbC, rfbA, rfbD, rfbB or wcaN, or
wcaM, wcaL, wcaK, wzxC, wcaJ, cpsG, cpsB, wcaI, gmm, fcl, gmd, wcaF, wcaE, wcaD, wcaC, wcaB, wcaA, wzc, wzb or wza,
cpsG, cpsB, fcl and gmd,
E. coli with either one or more regions that include:
the genes wcaJ, cpsG, cpsB, wcaI, gmm, fcl and gmd, and
the genes wbbK, wbbJ, wbbI, wbbH, glf, rfbX, frbC, rfbA, rfbD, rfbB, wcaN, wcaM, wcaL, wcaK, wzxC, wcaJ, cpsG, cpsB, wcaI, gmm, fcl, gmd, wcaF, wcaE, wcaD, wcaC, wcaB, wcaA, wzc, wzb and wza,
B. subtilis with deletions of all, part or of selected genes within the tagOABDFGH cluster,
and mutant strains bearing the genotypes:
ΔwcaM-wza,
ΔwbbK-wcaN,
ΔwbbL_2-wcaN,
ΔwbbK-wza,
ΔwbbL_2-wza, and
ΔwcaM-wza + Δrfe-rffM.
Regarding the level of skill and knowledge in the art of genetic modification, it is noted that the field of metabolic engineering can be inherently unpredictable and advances in metabolic pathway engineering are often achieved only by empirical experimentation. According to Guo et al. (Comp Struct Biotechnol J, 2017, 15:161; cited on the Form PTO-892 mailed 08/11/2025), “First, a lot of organisms are difficult to be engineered because of unknown regulation patterns and the lack of engineering tools for non-model organisms. Even for model microorganisms like Escherichia coli and Saccharomyces cerevisiae, which are well studied and equipped with a broad spectrum of biomolecular tools to allow metabolic engineering easily, the effects of heterologous expression of pathways are often unpredictable to guarantee a high productivity … Second, a key challenge in metabolic engineering is balancing the tug-of-war that exists between the cell's physiological and evolutionary objectives on one side and the engineer's process objectives on the other. Such conflict of resource allocation sometimes cannot be well addressed and toxic intermediates could be built up in the unbalanced pathway” [p. 162, column 1, middle].
Regarding the level of skill and knowledge in the art of amino acid modification, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the Form PTO-892 mailed 08/11/2025) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with residue substitution is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the Form PTO-892 mailed 08/11/2025), which discloses that even a substitution of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
In view of the high level of unpredictability in the art of genetic modification, acid modification, because the genus genetic modifications is widely variant with respect to both structure and function, and the specification discloses the actual reduction to practice of only sixteen representative species among a widely variant genus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus of genetically modified cells. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
Response to Remarks: beginning on page 17 of Applicant’s response to rejections under 35 USC 112(a); Applicant in summary contends the specification provides support for an organism modified to produce a glycosylated product regarding (a) genetic modification to include a heterologous glycosyltransferase, a nucleotide-sugar biosynthetic pathway, or a precursor-import system, (b) reduced or abolished expression of enzymes involved in cell-wall biosynthesis pathways, (c) representative species of E. coli, B. subtilis, C. glutamicum and C. reinhardtii, (d) the link between reduced cell wall biosynthesis and glycosylated product production and (e) definitions for “reduced or abolished expression”.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that the specification specifically defines “a cell genetically modified for the production of a glycosylated product” in the definitions [paras 0012-0081], the definitions section sets forth no such special definition, and independent claim 47 does not require the a cell to have a genetic modification to include a heterologous glycosyltransferase, a nucleotide-sugar biosynthetic pathway, or a precursor-import system. Claims 48-49, dependent from claim 47, recite the limitations of introducing one or more pathways for the synthesis of nucleotide-activated sugars and to express one or more glycosyltransferases, respectively. However, the specification includes one example a microorganism engineered with the genes from one organism for production of CMP-sialic acid [para 0353], which represents one nucleotide-sugar of the 19 listed in [para 0087], and therefore represents a single example of one biosynthetic pathway of a genus of biosynthetic pathways for the production of a genus of at least 19 nucleotide-sugars. Additionally, [para 0032] describes at least 13 classes of glycosyltransferases corresponding to a genus of glycosyltransferases widely variant with respect to structure and function, each of which considered a genus in its own right, from which Examples 15-17 [para 0468-0471] as cited by Applicant disclose 2 microorganisms comprising 6 glycosyltransferases from the variant genus of glycosyltransferases. Given these examples and limitations disclosed by the specification and in claims 48-49, the claims are still considered drawn to a genus of genetic modifications that are considered to be widely variant with respect to both structure and function in view of the limitation in claim 47 of a reduction of cell biosynthesis by deletion of at least one enzyme, or by reduced or abolished expression of at least one enzyme, as the examples cited by Applicant and limitations of claims 48-49 are not directed to this genus.
Regarding the assertion that the specification supports the reduced or abolished expression of enzymes involved in cell-wall biosynthesis pathways, and that the definition for “reduced or abolished expression” is established in the Definitions section [paras 0012-0081], there is no such definition for “reduced or abolished expression” set forth in the cited Definitions section. Applicant’s statement that the description of routine genetic-engineering techniques as exemplary methods of the achieving the “reduced or abolished expression” is acknowledged. These methods are considered exemplary methods, and therefore are not set forth as a special definition of the phrase as asserted by Applicant.
Regarding the assertion that the specification provides representative species of E. coli, B. subtilis, C. glutamicum and C. reinhardtii, these examples comprise 4 species from the widely variant genus of microorganisms recited in the claims, and are not considered sufficient to describe the widely variant genus of microorganism as set forth in the rejection above.
Regarding the assertion that the specification provides a link between reduced cell wall biosynthesis and glycosylated product production, this link relies upon the requirement for the claimed cell to have a genetic modification to include a heterologous glycosyltransferase, a nucleotide-sugar biosynthetic pathway, or a precursor-import system as stated by Applicant, wherein the claimed microorganisms are not required to have these genetic modifications as stated above.
As the reduction, reduced or abolished expression of at least one enzyme within the cell wall biosynthesis pathway recited in the claims does not recite any structural change to any specific gene in the recited pathways, the genetic modifications are considered to be structurally unlimited. Additionally, as the recited change in gene expression is not correlated to the function of producing of a glycosylated product, the genetic modifications are considered to be functionally unlimited. Therefore, the claimed reduction, reduced or abolished expression of at least one enzyme represents a genus of genetic modifications that are considered to be widely variant with respect to both structure and function, and one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus of genetically modified cells.
Claim Rejections - 35 USC § 101
Claims 47-54, 59-60 and 64-65 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Applicant’s attention is directed to the "Guidance for Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products”, released on December 16, 2014.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim Interpretation: The claims are drawn to a microorganism genetically modified for production of at least one glycosylated product, wherein the microorganism is a bacterium or yeast, and wherein the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway, which cell wall biosynthesis pathway is at least one pathway selected from the group consisting of: cell wall carbohydrate antigen biosynthesis, O-antigen biosynthesis or common-antigen biosynthesis when the microorganism is a Gram-negative bacterium, capsular polysaccharide biosynthesis, cell wall protein mannosylation biosynthesis, beta-1,3-glucan biosynthesis, beta-1,6-glucan biosynthesis and/or chitin biosynthesis when the microorganism is a yeast, mycolic acid and/or arabinogalactan biosynthesis when the microorganism is a Corynebacterium, Nocardia, or Mycobacterium, and teichoic acid biosynthesis when the microorganism is a Gram-positive bacterium.
The limitation in claim 47 of “[a] microorganism genetically modified for production of at least one glycosylated product” in the preamble is considered a Product-by-Process limitation according to MPEP 2113, wherein even though a product-by-process is limited by and defined by a process, determination of patentability is based on the product itself, and the patentability of a product does not depend on its method of production. Additionally, the phrase “genetically modified microorganism” does not impart any structural limitations on the claimed microorganism, such that one of skill in the art would recognize the “genetically modified microorganism” from its naturally occurring counterpart.
The preamble phrase “modified for production of at least one glycosylated product” in claim 47 is considered an intended use. According to MPEP 2111.02.II, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Additionally, “for the production of at least one glycosylated product” further limits the genetic modification that is the method of making the microorganism as described above.
The limitation in claim 47 of “the biosynthesis of the cell wall of the microorganism is reduced by a deletion, or by reduced or abolished expression of at least one enzyme within the cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell in the microorganism has not been reduced” is considered to be recited without a reference for comparison, and as such the limitation encompasses any activity of cell wall biosynthesis, and therefore any microorganism with any activity of cell wall biosynthesis. Additionally, the limitation of “reduced by a deletion, reduced, or abolished expression of at least one enzyme” is considered to further limit the Product-by-Process limitation described above, as it limits the method of producing the microorganism. Furthermore the limitation of “reduced, or abolished expression of at least one enzyme” considered a functional limitation as it is not drawn to any structural characteristic of the microorganism.
The limitation in claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of claim 47, which is considered a Product-by-Process limitation as discussed above, as the modification to introduce a pathway for nucleotide-activated sugar synthesis is a limitation of the method of producing the claimed microorganism.
The limitation in claim 49 of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of claim 47, which is considered a Product-by-Process limitation as discussed above, as the modification to express a glycosyltransferase is a limitation of the method of producing the claimed microorganism.
The limitation in claim 54 of “wherein the biosynthesis of the cell wall of a bacterium is additionally reduced by deletion of at least one enzyme within a further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a further cell wall biosynthesis pathway, compared to a bacterium lacking … reduced or abolished expression of at least one enzyme within the further cell wall synthesis pathway” is considered to further limit the Product-by-Process limitation of genetically modifying the cell as described above, and additionally is considered a functional limitation as it is not drawn to any structural characteristic of the microorganism.
The limitation in claim 59 of “wherein the biosynthesis of the cell wall of the bacterium has been additionally reduced by a reduced biosynthesis of colanic acid compared to a bacterium wherein the biosynthesis has not been reduced, wherein the reduced biosynthesis of colanic acid is provided by … reduced or abolished expression of at least one of the genes present in the biosynthesis gene cluster” is considered to further limit the Product-by-Process limitation of genetically modifying the cell as described above, and additionally is considered a functional limitation as it is not drawn to any structural characteristic of the microorganism.
Regarding claims 47-52 and 64-65, Galanos et al. (Eur J Biochem, 1985, 148:1; cited on the Form PTO-892 mailed 08/11/2025) discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. Furthermore, the E. coli of Galanos is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by the abstract of Mainprize et al. (J Biol Chem, 2013, 288:23064; cited on the Form PTO-892 mailed 08/11/2025).
Regarding claims 54 and 59-60, Maertens et al. (WO 2012/007481 A1; cited on the IDS filed 08/24/2022) discloses an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] involving knocking out colanic acid pathway genes that include wcaM [p 41, lines 19-20 and Figure 10], which is a putative colanic acid biosynthesis protein as evidenced by UniProt Accession No. WCAM_ECOLI (11/01/1997, 2 pages; cited on the Form PTO-892 mailed 08/11/2025), and as such teaches the naturally occurring E. coli strain containing the recited colanic acid biosynthesis genes.
Given a broadest reasonable interpretation, claims 47-52, 54, 59-60 and 64-65 are directed to a naturally-occurring E. coli strain.
Regarding claims 47 and 53, Martinez-Esparza et al. (J Immunol Method, 2006, 314:90; cited on the Form PTO-892 mailed 08/11/2025) discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. Given a broadest reasonable interpretation, claims 47 and 53 are directed to a naturally occurring S. cerevisiae strain.
Patent Eligibility Analysis Step 1: The claims are drawn to a composition of matter, which is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite a naturally occurring bacteria, which is considered to be a law of nature or natural phenomena (a natural product). Accordingly, claims 47-54, 59-60 and 64-65 are directed to a judicial exception.
Patent Eligibility Analysis Step 2A Prong 2: There are no additional elements recited in the claims beyond the judicial exception.
Patent Eligibility Analysis Step 2B: The claims only recite the product of nature, without more and do not include any additional elements that could add significantly more to the judicial exception.
As such, the claims do not qualify as eligible subject matter. For these reasons the claim is rejected under section 101 as being directed to non-statutory subject matter.
Response to Remarks: beginning on page 22 of Applicant’s response to rejections under 35 USC 101 entitled “Judicial Exception”; Applicant in summary contends the amendments to the claims overcome the rejection of record.
Applicant’s remarks are considered and found not convincing. As stated above, the claimed cell is considered to encompass a naturally occurring cell as disclosed by Galanos, Maertens, and Martinez.
Claim Rejections - 35 USC § 102
Claims 47-52, 54 and 64-65 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Galanos et al. (Eur J Biochem, 1985, 148:1; cited on the Form PTO-892 mailed 08/11/2025; herein referred to as Galanos) and evidentiary reference Mainprize et al. (J Biol Chem, 2013, 288:23064; cited on the Form PTO-892 mailed 08/11/2025; herein referred to as Mainprize).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 47 is drawn to a genetically modified microorganism genetically modified for production of at least one glycosylated product,
wherein the microorganism is a bacterium or yeast and has a cell wall,
wherein the biosynthesis of the cell wall is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell wall in the microorganism has not been reduced,
wherein the cell wall biosynthesis pathway is cell wall carbohydrate antigen biosynthesis.
The limitation in claim 47 of “a microorganism genetically modified for production of at least one glycosylated product” in the preamble is considered a Product-by-Process limitation according to MPEP 2113, wherein even though a product-by-process is limited by and defined by a process, determination of patentability is based on the product itself, and the patentability of a product does not depend on its method of production. The phrase “genetically modified microorganism” is drawn to the product-by-process limitation of genetically modifying a microorganism, and does not impart any structural limitations on the claimed microorganism.
The preamble phrase “modified for production of at least one glycosylated product” is considered an intended use. According to MPEP 2111.02.II, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Additionally, “for the production of at least one glycosylated product” further limits the genetic modification that is the method of making the microorganism as described above.
The limitation of “wherein the biosynthesis of the cell wall is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell wall in the microorganism has not been reduced” is considered to be recited without a reference for comparison as discussed in the 112(b) rejection above, and as such the limitation encompasses any activity of cell wall biosynthesis, and therefore any microorganism with any activity of cell wall biosynthesis. Additionally, the limitation of “reduced by a deletion, reduced, or abolished expression of at least one enzyme” is considered to further limit the Product-by-Process limitation described above, as it limits the method of producing the microorganism. Furthermore the limitation of “reduced, or abolished expression of at least one enzyme” considered a functional limitation as it is not drawn to any structural characteristic of the microorganism.
Claim 48 is drawn to the microorganism of claim 47, wherein the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways for the synthesis of one or more nucleotide-activated sugars.
The limitation in claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of claim 47, which is considered a Product-by-Process limitation as discussed above, as the modification to introduce a pathway for nucleotide-activated sugar synthesis is a limitation of the method of producing the claimed microorganism.
Claim 49 is drawn to the microorganism of claim 47, wherein the microorganism is further modified to express one or more glycosyltransferases for the production of the glycosylated product.
The limitation in claim 49 of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of claim 47, which is considered a Product-by-Process limitation as discussed above, as the modification to express a glycosyltransferase is a limitation of the method of producing the claimed microorganism.
Claim 50 is drawn to the microorganism of claim 47, wherein the glycosylated produce is an oligosaccharide, a glycosylated aglycon, a glycolipid, or a glycoprotein.
Claim 51 is drawn to the microorganism of claim 47, wherein the enzyme within the cell wall biosynthesis pathway is a glycosyltransferase.
Claim 52 is drawn to the microorganism of claim 47, wherein the microorganism is a bacterium selected from Escherichia, Bacillus, Lactobacillus, Lactococcus, and Corynebacterium.
Claim 54 is drawn to the microorganism of claim 47, wherein the microorganism is a bacterium, wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway, compared to a bacterium lacking deletion of at least one enzyme within the further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway, wherein the further biosynthesis pathway is selected from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof.
The limitation in claim 54 of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway, compared to a bacterium lacking deletion of at least one enzyme within the further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to be recited without a reference for comparison as described in the rejection under 112(b) above, and as such the limitation encompasses any activity of cell wall biosynthesis, and therefore any microorganism with any activity of cell wall biosynthesis from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof.
Claim 64 is drawn to the microorganism of claim 47, wherein the glycosylated product is an oligosaccharide with a degree of polymerization greater than 3.
Claim 65 is drawn to the microorganism of claim 47, wherein the microorganism is isolated.
Galanos relates to Escherichia coli lipid A [title].
Regarding claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of claims 47, 50 and 52.
Regarding claim 48, as the limitation in claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of claim 49.
Regarding claim 54, as the limitation in claim 54 of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of claim 54.
Regarding claim 64, the claim further limits the intended use of the microorganism of claim 47 as stated above, but does not structurally limit the microorganism of claim 47. Therefore the rejection of claim 64 is included with the rejection of claim 47.
Regarding claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
For these reasons, Galanos anticipates claims 47-52, 54 and 64-65.
Claims 47 and 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Martinez-Esparza et al. (J Immunol Method, 2006, 314:90; cited on the Form PTO-892 mailed 08/11/2025; herein referred to as Martinez).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 47 is drawn to a genetically modified microorganism genetically modified for production of at least one glycosylated product,
wherein the microorganism is a bacterium or yeast and has a cell wall,
wherein the biosynthesis of the cell wall is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell wall in the microorganism has not been reduced,
wherein the cell wall biosynthesis pathway is cell wall carbohydrate antigen biosynthesis.
The limitation in claim 47 of “a microorganism genetically modified for production of at least one glycosylated product” in the preamble is considered a Product-by-Process limitation according to MPEP 2113, wherein even though a product-by-process is limited by and defined by a process, determination of patentability is based on the product itself, and the patentability of a product does not depend on its method of production. The phrase “genetically modified microorganism” is drawn to the product-by-process limitation of genetically modifying a microorganism, and does not impart any structural limitations on the claimed microorganism.
The preamble phrase “modified for production of at least one glycosylated product” is considered an intended use. According to MPEP 2111.02.II, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Additionally, “for the production of at least one glycosylated product” further limits the genetic modification that is the method of making the microorganism as described above.
The limitation of “wherein the biosynthesis of the cell wall is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell wall in the microorganism has not been reduced” is considered to be recited without a reference for comparison as discussed in the 112(b) rejection above, and as such the limitation encompasses any activity of cell wall biosynthesis, and therefore any microorganism with any activity of cell wall biosynthesis. Additionally, the limitation of “reduced by a deletion, reduced, or abolished expression of at least one enzyme” is considered to further limit the Product-by-Process limitation described above, as it limits the method of producing the microorganism. Furthermore the limitation of “reduced, or abolished expression of at least one enzyme” considered a functional limitation as it is not drawn to any structural characteristic of the microorganism.
Claim 53 is drawn to the microorganism of claim 47, wherein the microorganism is a yeast selected from the group consisting of Pichia, Hansenula, Komagataella, and Saccharomyces.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of claims 47 and 53.
For these reasons, Martinez anticipates claims 47 and 53.
Claims 47, 54 and 59-60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maertens et al. (WO 2012/007481 A1; cited on the IDS filed 08/24/2022; herein referred to as Maertens) and evidentiary references UniProt Accession No. WCAM_ECOLI (11/01/1997, 2 pages; cited on the Form PTO-892 mailed 08/11/2025; herein referred to as UNI1) and Galanos.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 47 is drawn to a genetically modified microorganism genetically modified for production of at least one glycosylated product,
wherein the microorganism is a bacterium or yeast and has a cell wall,
wherein the biosynthesis of the cell wall is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell wall in the microorganism has not been reduced,
wherein the cell wall biosynthesis pathway is cell wall carbohydrate antigen biosynthesis.
The limitation in claim 47 of “a microorganism genetically modified for production of at least one glycosylated product” in the preamble is considered a Product-by-Process limitation according to MPEP 2113, wherein even though a product-by-process is limited by and defined by a process, determination of patentability is based on the product itself, and the patentability of a product does not depend on its method of production. The phrase “genetically modified microorganism” is drawn to the product-by-process limitation of genetically modifying a microorganism, and does not impart any structural limitations on the claimed microorganism.
The preamble phrase “modified for production of at least one glycosylated product” is considered an intended use. According to MPEP 2111.02.II, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Additionally, “for the production of at least one glycosylated product” further limits the genetic modification that is the method of making the microorganism as described above.
The limitation of “wherein the biosynthesis of the cell wall is reduced by a deletion of at least one enzyme within a cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within a cell wall biosynthesis pathway compared to a microorganism wherein the biosynthesis of the cell wall in the microorganism has not been reduced” is considered to be recited without a reference for comparison as discussed in the 112(b) rejection above, and as such the limitation encompasses any activity of cell wall biosynthesis, and therefore any microorganism with any activity of cell wall biosynthesis. Additionally, the limitation of “reduced by a deletion, reduced, or abolished expression of at least one enzyme” is considered to further limit the Product-by-Process limitation described above, as it limits the method of producing the microorganism. Furthermore the limitation of “reduced, or abolished expression of at least one enzyme” considered a functional limitation as it is not drawn to any structural characteristic of the microorganism.
Claim 54 is drawn to the microorganism of claim 47, wherein the microorganism is a bacterium, wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway, compared to a bacterium lacking deletion of at least one enzyme within the further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway, wherein the further biosynthesis pathway is selected from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof.
The limitation in claim 54 of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway, compared to a bacterium lacking deletion of at least one enzyme within the further cell wall biosynthesis pathway, or by reduced or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to be recited without a reference for comparison as described in the rejection under 112(b) above, and as such the limitation encompasses any activity of cell wall biosynthesis, and therefore any microorganism with any activity of cell wall biosynthesis from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof.
Claim 59 is drawn to the microorganism of claim 54, wherein the microorganism is a bacterium having further reduced cell wall biosynthesis by a reduced colanic acid biosynthesis, wherein the reduction in the colanic acid biosynthesis is provided by a deletion, reduced or abolished expression of at least one of the genes present in the colanic acid biosynthesis gene cluster comprising putative colanic acid biosynthesis protein.
The limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a reduced biosynthesis of colanic acid compared to a bacterium wherein the biosynthesis has not been reduced, wherein the reduced biosynthesis of colanic acid is provided by a deletion or by reduced or abolished expression of at least one of the genes present in the colanic acid gene cluster” is considered a Product-by-Process limitation as discussed above, as the modification of a deletion, reduced or abolished expression of at least one of the genes present in the colanic acid biosynthesis gene cluster is a limitation of the method of producing the claimed microorganism. Additionally the limitation of is considered to be recited without a reference for comparison as discussed in the rejection under 112(b), and as such the limitation encompasses any activity of colanic acid biosynthesis, and therefore encompasses a microorganism with any colanic acid biosynthesis.
Claim 60 is drawn to the microorganism of claim 59, wherein the reduction in colanic acid synthesis is provided by a deletion, reduced or abolished expression of i) WcaM, optionally as given by SEQ ID NO: 39, or ii) a polypeptide having 80% or more sequence identity to the full-length sequence of SEQ ID NO: 39 and having colanic acid biosynthesis activity
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of claims 47, 54 and 59-60.
For these reasons, Maertens anticipates claims 47, 54 and 59-60.
Response to Remarks: beginning on page 22 of Applicant’s response to rejections under 35 USC 102(a)(1); Applicant in summary contends the amended claims require two coordinated genetic features involving the production of a glycosylated product and a defined reduction of cell wall biosynthesis activity that is not disclosed by any of the prior art of record.
Applicant’s remarks are considered and found not convincing. As stated in the rejection and the claim interpretations set forth above, the claimed cell is not required to have any structurally distinct genetic modifications in view of the limitation allowing the reduced activity to result from “reduced or abolished expression of a gene”. Additionally, the claimed cell is not required to have any defined reduction in cell wall biosynthesis activity, in view of the lack of a recited reference for comparison of activity, and therefore limitations regarding the level of activity are considered to encompass any activity of the recited cell wall biosynthetic activity in the claims. In view of these interpretations, the cell of Galanos, and the cell of Martinez, and the cell of Maertens are considered to anticipate the claimed cell for the reasons set forth in the rejections above.
Double Patenting
The provisional rejections on the ground of nonstatutory double patenting over co-pending application 17/904196 (rejection E) set forth in the previous Office action are withdrawn in view of the abandonment of the application.
A. Claims 47-54, 59-60 and 64-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 and 29 of U.S. Patent No. 9,701,992 (cited on the Form PTO-892 mailed 08/11/2025; herein “patent”) and evidentiary references Galanos, Mainprize, Maertens, Martinez and UNI1. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claims 47-54, 59-60, claim 1 of the patent recites a metabolically engineered bacterium or yeast for the production of fucosyllactose, and claim 4 of the patent recites the bacterium is E. coli and the yeast is S. cerevisiae, which is considered to correspond to an E. coli bacterium that produces the lipopolysaccharide component Lipid A which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1], and therefore is a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid as evidenced by Galanos (corresponding to instant claims 47, 50, 52 and 54), wherein the production of Lipid A inherently involves the expression of a glycosyltransferase (corresponding to instant claims 49 and 51), and wherein the E. coli is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract] (corresponding to claim 48), and is understood to contain the gene wcaM that is a putative colanic acid pathway gene as evidenced by Maertens [p 41, lines 19-20 and Figure 10] and UNI1 (corresponding to instant claims 59-60).
B. Claims 47-54, 59-60 and 64-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 10,570,430 (cited on the Form PTO-892 mailed 08/11/2025; herein “patent”) and evidentiary references Galanos, Mainprize, Maertens, Martinez and UNI1. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claims 47-54, 59-60, claim 1 of the patent recites a metabolically engineered bacterium or yeast for the production of fucosyllactose, and claim 4 of the patent recites the bacterium is E. coli and the yeast is S. cerevisiae, which is considered to correspond to an E. coli bacterium that produces the lipopolysaccharide component Lipid A which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1], and therefore is a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid as evidenced by Galanos (corresponding to instant claims 47, 50, 52 and 54), wherein the production of Lipid A inherently involves the expression of a glycosyltransferase (corresponding to instant claims 49 and 51), and wherein the E. coli is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract] (corresponding to claim 48), and is understood to contain the gene wcaM that is a putative colanic acid pathway gene as evidenced by Maertens [p 41, lines 19-20 and Figure 10] and UNI1 (corresponding to instant claims 59-60).
Additionally, claims 1 and 4 of the patent correspond to a yeast that produces glycans such as mannans, wherein the surface expression of such glycans is related to virulence as evidenced by Martinez [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway (corresponding to claim 53).
Regarding instant claim 64, the instant claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, claim 1 of the patent recites the microorganism has been genetically modified to disrupt endogenous genes, which is considered to encompass an isolated microorganism.
Additionally, claims 1 and 4 of the patent correspond to a yeast that produces glycans such as mannans, wherein the surface expression of such glycans is related to virulence as evidenced by Martinez [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway (corresponding to claim 53).
Regarding instant claim 64, the instant claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, claim 29 of the patent recites cultivating the bacterium or yeast, which is considered to encompass an isolated microorganism.
C. Claims 47-52, 54 and 64-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,077,788 (cited on the Form PTO-892 mailed 08/11/2025; herein “patent”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the patent recites a metabolically engineered cell the produces fucosylated oligosaccharides, wherein fucosylated oligosaccharides are understood to be glycosylated products.
The claims of the patent do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the patent and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the patent with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
Claims 47 and 53 are rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,077,788 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the patent recites a metabolically engineered cell the produces fucosylated oligosaccharides, wherein fucosylated oligosaccharides are understood to be glycosylated products.
The claims of the patent do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the patent and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the patent with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Martinez discuss cells that can produce glycosylated products.
Claims 47, 54 and 59-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,077,788 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the patent recites a metabolically engineered cell the produces fucosylated oligosaccharides, wherein fucosylated oligosaccharides are understood to be glycosylated products.
The claims of the patent do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the patent and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the patent with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Maertens discuss cells that can produce glycosylated products.
D. Claims 47-52, 54 and 64-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,123,041 (cited on the Form PTO-892 mailed 08/11/2025; herein “patent”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the patent recites a method of producing a UDP-N-acetylglucosamine-derived saccharide in a gram-negative bacterium, which is understood to be a glycosylated product.
The claims of the patent do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the patent and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the patent with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
Claims 47 and 53 are rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,123,041 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the patent recites a method of producing a UDP-N-acetylglucosamine-derived saccharide in a gram-negative bacterium, which is understood to be a glycosylated product.
The claims of the patent do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the patent and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the patent with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Martinez discuss cells that can produce glycosylated products.
Claims 47, 54 and 59-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,123,041 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the patent recites a method of producing a UDP-N-acetylglucosamine-derived saccharide in a gram-negative bacterium, which is understood to be a glycosylated product.
The claims of the patent do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the patent by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the patent and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the patent with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Maertens discuss cells that can produce glycosylated products.
F. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 100 of co-pending application 18/040332 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 100 of the reference application recites a cell that produces oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 100 of co-pending application 18/040332 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 100 of the reference application recites a cell that produces oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 100 of co-pending application 18/040332 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 100 of the reference application recites a cell that produces oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
G. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 101 of co-pending application 18/040356 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 101 of the reference application recites a cell that produces sialylated oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 101 of co-pending application 18/040356 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 101 of the reference application recites a cell that produces sialylated oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 101 of co-pending application 18/040356 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 101 of the reference application recites a cell that produces sialylated oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
H. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of co-pending application 18/040602 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method of producing a glycosylated form of fucose-alpha-1,2-galacose-R by a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of co-pending application 18/040602 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method of producing a glycosylated form of fucose-alpha-1,2-galacose-R by a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of co-pending application 18/040602 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method of producing a glycosylated form of fucose-alpha-1,2-galacose-R by a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
I. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of co-pending application 18/041064 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method to produce oligosaccharides by a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of co-pending application 18/041064 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method to produce oligosaccharides by a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of co-pending application 18/041064 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method to produce oligosaccharides by a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
J. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 52 of co-pending application 18/041137 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 52 of the reference application recites a cell metabolically engineered to produce sialylated disaccharide, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 52 of co-pending application 18/041137 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 52 of the reference application recites a cell metabolically engineered to produce sialylated disaccharide, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 52 of co-pending application 18/041137 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 52 of the reference application recites a cell metabolically engineered to produce sialylated disaccharide, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
K. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 80 of co-pending application 18/041154 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 80 of the reference application recites a cell for producing oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 80 of co-pending application 18/041154 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 80 of the reference application recites a cell for producing oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 80 of co-pending application 18/041154 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 80 of the reference application recites a cell for producing oligosaccharides, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
L. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 109 of co-pending application
cation 18/041167 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 109 of the reference application recites a method for producing an oligosaccharide using a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 109 of co-pending application 18/041167 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 109 of the reference application recites a method for producing an oligosaccharide using a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 109 of co-pending application 18/041167 in view of Maertens and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 109 of the reference application recites a method for producing an oligosaccharide using a cell, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
M. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of co-pending application 18/167687 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method for producing a galactosylated disaccharide, which is understood to be a glycosylated product, and claim 5 recites the disaccharide is produced by a cell.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of co-pending application 18/167687 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method for producing a galactosylated disaccharide, which is understood to be a glycosylated product, and claim 5 recites the disaccharide is produced by a cell.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of co-pending application 18/167687 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method for producing a galactosylated disaccharide, which is understood to be a glycosylated product, and claim 5 recites the disaccharide is produced by a cell.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
N. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 78 of co-pending application 18/254345 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 78 of the reference application recites a metabolically engineered cell for producing a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 78 of co-pending application 18/254345 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 63 of the reference application recites a metabolically engineered cell for producing a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 78 of co-pending application 18/254345 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 63 of the reference application recites a metabolically engineered cell for producing a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
O. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 27 of co-pending application 18/261793 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 27 of the reference application recites a metabolically engineered cell for producing a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 27 of co-pending application 18/261793 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 27 of the reference application recites a metabolically engineered cell for producing a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 27 of co-pending application 18/261793 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 27 of the reference application recites a metabolically engineered cell for producing a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
P. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 46 of co-pending application 18/261806 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 46 of the reference application recites a genetically modified cell for producing an oligosaccharide, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 46 of co-pending application 18/261806 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 46 of the reference application recites a genetically modified cell for producing an oligosaccharide, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 46 of co-pending application 18/261806 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 46 of the reference application recites a genetically modified cell for producing an oligosaccharide, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Q. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 61 of co-pending application 18/555611 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 61 of the reference application recites a cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 61 of co-pending application 18/555611 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 61 of the reference application recites a cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 61 of co-pending application 18/555611 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 61 of the reference application recites a cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
R. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 57 of co-pending application 18/555649 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 57 of the reference application recites a metabolically engineered cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 57 of co-pending application 18/555649 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 57 of the reference application recites a metabolically engineered cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 57 of co-pending application 18/555649 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 57 of the reference application recites a metabolically engineered cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
S. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 54 of co-pending application 18/555663 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 54 of the reference application recites a metabolically engineered cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 54 of co-pending application 18/555663 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 54 of the reference application recites a metabolically engineered cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 54 of co-pending application 18/555663 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 54 of the reference application recites a metabolically engineered cell for producing an oligosaccharide compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
T. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of co-pending application 18/718677 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method for producing a fucosylated compound, which is understood to be a glycosylated product, and claim 10 of the reference application recites the method is carried out in the cell.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of co-pending application 18/718677 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method for producing a fucosylated compound, which is understood to be a glycosylated product, and claim 10 of the reference application recites the method is carried out in the cell.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of co-pending application 18/718677 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 1 of the reference application recites a method for producing a fucosylated compound, which is understood to be a glycosylated product, and claim 10 of the reference application recites the method is carried out in the cell.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
U. Claims 47-52, 54 and 64-65 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 114 of co-pending application 18/720533 (herein “reference application”) in view of Galanos and evidentiary reference Mainprize.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 114 of the reference application recites a metabolically engineered cell for producing a fucosylated compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding cell wall biosynthesis pathway wherein the pathway is cell wall carbohydrate biosynthesis.
Galanos relates to Escherichia coli lipid A [title].
Regarding instant claims 47, 50 and 52, Galanos discloses endotoxin lipopolysaccharides of Gram-negative bacteria such as E. coli consist of a Lipid A component which elicits multiple acute pathophysiological effects such as fever and macrophage and B-lymphocyte activation [p 1, col 1, para 1]. In view of the interpretation of the limitations “a microorganism genetically modified for production of at least one glycosylated product” and “the microorganism has a cell wall biosynthesis that is reduced by a deletion, reduced, or abolished expression of at least one enzyme within the cell wall biosynthesis pathway” set forth above, Galanos is considered to disclose a bacterium with a cell wall carbohydrate antigen biosynthesis pathway understood to comprise at least one active gene, wherein the bacterium is able to produce a glycolipid. As such, the disclosure of Galanos is considered to satisfy the limitations of instant claims 47, 50 and 52.
In view of Galanos, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Galanos, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Galanos are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Galanos, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Galanos discuss cells that can produce glycosylated products.
Regarding instant claim 48, as the limitation in instant claim 48 of “the reduced cell wall biosynthesis pathway is combined with the introduction of one or more pathways” is considered to further limit the preamble of instant claim 47 as drawn to the method of producing the claimed microorganism, the structural limitations on the cell of instant claim 48 imparted by the process is considered to be that the cell contains a pathway for the synthesis of one or more nucleotide-activated sugars. Galanos discloses the bacterial microorganism E. coli described above, which is understood to contain the pathway for producing the nucleotide-activated sugar UDP-glucuronic acid as evidenced by Mainprize [abstract].
Regarding instant claims 49 and 51, as the limitation of “the microorganism is further modified to express one or more glycosyltransferases” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 49 imparted by the process is considered to be that the microorganism contains a glycosyltransferase. The instant specification defines a glycosyltransferase as “an enzyme capable to catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds” [para 0031]. As Galanos discloses Lipid A is shown in [Figure 1] to have glycosidic bonds, the bacterium of Galanos is considered to inherently possess glycosyltransferase enzymes for the synthesis of Lipid A, and as such disclosure of Galanos is considered to satisfy the limitations of instant claim 49.
Regarding instant claim 54, as the limitation of “wherein the biosynthesis of the cell wall of the bacterium is additionally reduced by a deletion, reduced, or abolished expression of at least one enzyme within the further cell wall biosynthesis pathway” is considered to further limit the preamble of instant claim 47 as it is drawn to the method of producing the claimed microorganism, the structural limitation on the microorganism of instant claim 54 imparted by the process is considered to be that the microorganism is a bacterium that that has cell wall biosynthesis activity from the group consisting of colanic acid biosynthesis, exopolysaccharide biosynthesis, lipopolysaccharide biosynthesis, and any combination thereof. As the limitation of “reduced activity” is considered to be recited without a reference for comparison as described in the 112(b) rejection above, the limitation encompasses any activity of cell wall biosynthesis from the recited groups of cell wall biosynthesis pathways. As Galanos discloses the E. coli bacterium above that contains the activity to synthesize Lipid A as part of lipopolysaccharide, Galanos satisfies the limitations of instant claim 54.
Regarding instant claim 64, the claim further limits the intended use of the microorganism of instant claim 47 as stated above, but does not structurally limit the microorganism of instant claim 47. Therefore the rejection of instant claim 64 is included with the rejection of instant claim 47.
Regarding instant claim 65, Galanos discloses E. coli strain F515 [p 1, col 2, para 2], which is understood to be an isolate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47 and 53 are provisionally rejected are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 114 of co-pending application 18/720533 in view of Martinez.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 114 of the reference application recites a metabolically engineered cell for producing a fucosylated compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite limitations regarding a yeast microorganism.
Martinez relates to cell wall surface glycan expression in Candida albicans and Saccharomyces cerevisiae yeasts [title].
Regarding instant claims 47 and 53, Martinez discloses yeast cell walls are composed of glycans, wherein the outermost layers are composed of phosphopeptidomannan which is referred to as mannans [p 91, col 1, para 3]. Martinez further discloses that C. albicans and the non-pathogenic S. cerevisiae both produce mannans, and that there are variations in mannans related to both chain length and antigenicity [p 91, col 1, para 3 to col 2, para 1], wherein the surface expression of such glycans is related to virulence [abstract]. Therefore, Martinez discloses the production of mannans in the yeast C. albicans and S. cerevisiae, which is considered to correspond to a cell wall antigen synthesis pathway. In view of the interpretations of the limitations in instant claim 47 set forth above, the S. cerevisiae of Martinez is considered to satisfy the limitations of instant claims 47 and 53.
In view of Martinez, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Martinez, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Martinez are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Martinez, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Martinez discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 47, 54 and 59-60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 114 of co-pending application 18/720533 and evidentiary reference UNI1.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 47, claim 114 of the reference application recites a metabolically engineered cell for producing a fucosylated compound, which is understood to be a glycosylated product.
The claims of the reference application do not recite the limitations regarding the colanic acid biosynthesis pathway.
Maertens relates to metabolically engineered organisms for the production of bio-products [title] such as glycolipid, glycoside, nucleoside and glycoprotein [abstract].
Regarding instant claims 47, 54 and 59-60, Maertens teaches an E. coli genetically modified to produce fucosylated sugars in Example 15 [p 41, starting line 14] that requires the modification of the colanic acid pathway comprising genes that include wcaM, which is a putative colanic acid biosynthesis protein as evidenced by UNI1, wherein the genetic modification includes knockouts [p 41, lines 19-20 and Figure 10]. In view of the interpretations set forth above, as E. coli is understood to produce the glycosylated product of the cell wall antigen Lipid A as part of lipopolysaccharide as evidenced by Galanos [p 1, col 1, para 1], the E. coli of Maertens satisfies the limitations of instant claims 47, 54 and 59-60.
In view of Maertens, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the claims of the reference application by using the microorganism of Maertens, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the cell of the reference application and the microorganism of Maertens are cells that produce glycosylated products. Thus it would have been obvious to one of ordinary skill in the art to replace the cell of the reference application with the microorganism of Maertens, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Maertens discuss cells that can produce glycosylated products.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks: beginning on page 29 of Applicant’s response to double patenting rejections; Applicant in summary contends the inventions of U.S. Patent Nos. 9,701,992, 10,570,430, 12,077,788, 12,123,041, and co-pending application Nos. 18/040332, 18/040356, 18/040602, 18/041064, 18/041137, 18/041154, 18/041167, 18/167687, 18/254345, 18/261793, 18/261806, 18/555611, 18/555649, 18/555663, 18/718677, and 18/720533, corresponding to rejections A-D and F-U described in the section above, are patentably distinct as the instant application is drawn to distinct mutations not recited by the conflicting patents and co-pending applications, and the instant application is drawn to a different scope of products than the conflicting patents and co-pending applications.
Applicant’s remarks are considered and found not convincing. As stated in the rejections above, the instant claims are drawn to a cell for the production of a genus of glycosylated products, and each of the conflicting patents and co-pending applications are drawn to a cell for the production of either the genus of glycosylated products or species from the genus of glycosylated products. In view of the claim interpretations set forth in the Office action above, the instantly claimed cell is not required to have any structurally distinct genetic modifications to the genes or pathways recited in the instant claims, and therefore the cells disclosed by the conflicting patents and co-pending applications in addition to the cited art are considered to satisfy the limitations of the instant claims for the reasons set forth in the rejections above.
Conclusion
Status of the Application:
Claims 47-69, 71-74, 76-84 and 93-110 are pending.
Claims 55-58, 61-63, 66-69, 71-74, 76-84 and 93-110 are withdrawn.
Claims 47-54, 59-60 and 64-65 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656