DETAILED ACTION
Status of the Application
Claims 1-6, 8-14 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claim 4, cancellation of claim 7, and addition of claims 10-14 as submitted in a communication filed on 1/7/2026 is acknowledged.
Applicant’s election without traverse of Group II, claims 7-9, drawn to a method for producing an oligosaccharide of interest, and the election without traverse of the oligosaccharide lacto-N-neotetraose (LNnT) as submitted in a communication filed on 1/7/2026 is acknowledged.
New claims 10-14 are directed to the elected invention. Claims 1-6 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1/7/2026.
Claims 8-14 are at issue and will be examined to the extent they encompass the elected invention.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See page 24, line 20. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01.
Priority
Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to EUROPEAN PATENT OFFICE (EPO) EP20182737.5 filed on 06/26/2020. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
This is the US national application which entered the national stage from PCT/EP2021/065765 filed on 06/11/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/27/2022, 3/27/2023, 10/24/2023, and 11/29/2023 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 12/27/2022 have been reviewed and are accepted by the Examiner for examination purposes.
Claim Objections
Claim 9 is objected to due to the recitation of “…method … an oligosaccharide of interest from a gram-negative bacterial cell into a culture medium said bacterial cell is cultured in..”. To enhance clarity and to be consistent with commonly used claim language, the claim should be amended to recite “…method …an oligosaccharide of interest from a gram-negative bacterial cell into a culture medium, wherein the bacterial cell has been genetically…”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 8 (claims 10-14 dependent thereon) is indefinite in the recitation of “a) providing a …bacterial cell, wherein the bacterial cell – possesses a cytoplasm…outer membrane, - is able to synthesize the oligosaccharide of interest” for the following reasons. As written, it is unclear if the two limitations recited with regard to the bacterial cell are required or if only one of them is required in view of the fact that there is no “and” or “or” between the terms “outer membrane” and “is able to synthesize”. For examination purposes, it will be assumed that the limitations are in the alternative (i.e., “or”). Correction is required.
Claim 9 is indefinite in the recitation of “..method for enhancing the export of an oligosaccharide of interest …” for the following reasons. The term “enhancing” is unclear in the absence of a reference to determine if “enhancement” is present (i.e., enhanced compared to what?). For examination purposes, no patentable weight will be given to the term “enhancing” and it will be assumed that the method of claim 9 is a method for exporting an oligosaccharide of interest. Correction is required.
Claim 11 is indefinite in the recitation of “preferably from the group consisting of….” for the following reasons. The term “preferably” renders the claim indefinite because it is unclear whether the limitations following the term are part of the claimed invention. As written, it is unclear if the human milk oligosaccharides are limited those recited after the term “group consisting of”. For examination purposes, no patentable weight will be given to the term “preferable from the group consisting of…..”. Correction is required.
Claim 12 is indefinite in the recitation of “wherein the saccharide transporter is an endogenous transporter or a non-endogenous transporter and/or wherein the porin is an endogenous porin or a non-endogenous porin” for the following reasons. A protein is either endogenous or non-endogenous. Therefore, it is unclear as to how the terms “endogenous transporter or non-endogenous transporter” and “endogenous porin or non-endogenous porin” further limit the transporter and the porin if the options are all inherently encompassed. For examination purposes, claim 12 will be interpreted as a duplicate of claim 8. Correction is required.
Claim 13 is indefinite in the recitation of “…genetically engineered to overexpress the endogenous saccharide transporter and/or the endogenous porin” for the following reasons. There is no antecedent basis for the endogenous saccharide transporter or the endogenous porin. In addition, the term “overexpress” is a relative term and the claim fails to provide the required reference to make a determination of “overexpression” (e.g., overexpressed compared to what?). If the intended limitation is “to express”, the claim should be amended accordingly. For examination purposes, claim 13 will be interpreted as a duplicate of claim 8. Correction is required.
Claim 14 is indefinite in the recitation of “..to express the non-endogenous saccharide transporter and/or the non-endogenous porin” for the following reasons. There is no antecedent basis for the non-endogenous transporter and the non-endogenous porin. For examination purposes, it will be assumed that claim 14 is a duplicate of claim 8. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 8-14 are directed in part to a method for producing a genus of human milk oligosaccharides having any structure wherein said method requires culturing a genus of gram-negative bacterial cells modified by any means such that they can produce said genus of human milk oligosaccharides, wherein said bacterial cells express a genus of saccharide transporters and/or porins having any structure, and wherein said bacterial cell has been modified by any means to deregulate the expression of any endogenous porin or saccharide transporter. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims require a potentially large genus of (i) unknown modifications that can be made to any gram-negative bacterial cell so that it can produce any human milk oligosaccharide, (ii) unknown nucleic acids encoding enzymes having any structure and function, wherein said enzymes are part of any human milk oligosaccharide biosynthetic pathway, (iii) unknown nucleic acids encoding any saccharide transporter and/or porin, and (iv) unknown modifications to deregulate the expression of endogenous porins and/or saccharide transporters.
While the claims encompass the expression of a genus of genes encoding structurally and functionally unrelated enzymes/proteins, the specification is silent with regard to the structural features required in any gene that encodes an enzyme/protein that could be used for the synthesis of any human milk oligosaccharide, or the structural features required in any gene encoding any porin or saccharide transporter. Furthermore, while the claims require unknown modifications to deregulate the expression of any endogenous porin or saccharide transporter in any gram-negative cell, the specification discloses using a heterologous promoter and increasing the copy number of a gene as the only modifications that would deregulate its expression. The specification is silent with regard to other genetic modifications that could be made to deregulate expression of an endogenous gene, such as structural modifications to promoters, the expression of proteins that could act as enhancers of transcription, the structure/identity of expression inducers of the desired gene, antisense molecules to block expression of genes that inhibit the expression of the desired gene, or structural modifications to the coding region of a gene to alter the activity of the protein encoded by the target gene. The specification fails to provide a structure/function correlation that would allow one of skill in the art to recognize those genes that encode the enzymes required to produce any human milk oligosaccharide in any gram-negative cell, a structure/function correlation that would allow one of skill in the art to recognize those genes that encode any porin or saccharide transporter, or the genetic modifications required in any gram-negative cell to produce the desired oligosaccharide in a gram-negative cell.
A sufficient written description of a genus of genes/proteins may be achieved by a recitation of a representative number of genes/proteins defined by their nucleotide/amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no recited structural feature and there is no art-recognized correlation between structure and function which would provide those unknown structural features. In addition, while one could argue that sequences disclosed in the prior art are representative of the structure of all the members of the genus of genes/proteins required, it is noted that the art teaches several examples of differences in activity even when there is little structural variability. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Therefore, since minor structural differences may result in different function, and no additional information correlating structure with the desired activity has been provided, one cannot reasonably conclude that the genes/proteins of the prior art are representative of all the members of the genus of porins/saccharide transporters and proteins required to produce the required human milk oligosaccharides in a gram-negative cell as recited.
Due to the fact that the specification only discloses a very limited number of enzymes that can be used to produce a limited number of oligosaccharides, a limited number of porins and saccharide transporters, a very limited number of modifications to deregulate the expression of an endogenous gene, and a single gram-negative organism that is able to produce a limited number of oligosaccharides, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 8-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for producing lacto-N-neotetraose by culturing an E. coli cell that has been transformed with the N. meningitidis lgtA gene, the A. segnis lex-1 gene, and the E. coli pgm, galE, lacY and galU genes, wherein said E. coli cell comprises deletions in the endogenous wcaJ, lacZ, lacA, nagB, waaB, and mdoH genes, and wherein said E. coli cell has been transformed with a porin gene selected from the E. coli ompF gene, the E. coli scrY gene, the K. pneumoniae scrY gene, the E. coli ompC gene, the S. enterica ompA gene, and the S. enterica ompN-ompC genes, and the E. coli cell has been transformed with a saccharide transporter gene selected from the E. coli mdtM gene, the S. lincolnensis lmrC gene, a P. carotovorum gene encoding the protein disclosed in GenBank accession No. ZP_03829909, the G. anatis ydeE gene, a Pseudomonas sp. MT-1 gene encoding the protein disclosed in GenBank accession No. BAP78849, and a Beeauveria bassiana D1-5 gene encoding the protein disclosed in GenBank accession No. KGQ13398, does not reasonably provide enablement for a method for producing any human milk oligosaccharide having any structure wherein said method requires culturing any gram-negative bacterial cell modified by any means such that it can produce said human milk oligosaccharide, wherein said bacterial cell expresses any saccharide transporter and/or porin having any structure, and wherein said bacterial cell has been modified by any means to deregulate the expression of any endogenous porin and/or saccharide transporter. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breadth of the claims. The factors that have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 8-14 broadly encompass a method for producing any human milk oligosaccharide having any structure wherein said method requires culturing any gram-negative bacterial cell modified by any means such that it can produce said human milk oligosaccharide, wherein said bacterial cell expresses any saccharide transporter and/or porin having any structure, and wherein said bacterial cell has been modified by any means to deregulate the expression of any endogenous porin or saccharide transporter. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
The enablement provided is not commensurate in scope with the claims due to the large number of unknown modifications one could make to any gram-negative bacterial cell so that it can produce any human milk oligosaccharide, the large number of unknown genes encoding enzymes that could be used to produce any human milk oligosaccharide in any gram-negative bacterial cell, the large number of unknown porins and saccharide transporters required by the gram-negative bacterial cell of the claims, and the large number of unknown modifications one could make to deregulate the expression of an endogenous gene. In the instant case, the specification enables a method for producing lacto-N-neotetraose by culturing an E. coli cell that has been transformed with the N. meningitidis lgtA gene, the A. segnis lex-1 gene, and the E. coli pgm, galE, lacY and galU genes, wherein said E. coli cell comprises deletions in the endogenous wcaJ, lacZ, lacA, nagB, waaB, and mdoH genes, and wherein said E. coli cell has been transformed with a porin gene selected from the E. coli ompF gene, the E. coli scrY gene, the K. pneumoniae scrY gene, the E. coli ompC gene, the S. enterica ompA gene, and the S. enterica ompN-ompC genes, and the E. coli cell has been transformed with a saccharide transporter gene selected from the E. coli mdtM gene, the S. lincolnensis lmrC gene, a P. carotovorum gene encoding the protein disclosed in GenBank accession No. ZP_03829909, the G. anatis ydeE gene, a Pseudomonas sp. MT-1 gene encoding the protein disclosed in GenBank accession No. BAP78849, and a Beeauveria bassiana D1-5 gene encoding the protein disclosed in GenBank accession No. KGQ13398.
The amount of direction or guidance presented and the existence of working examples. The specification discloses an E. coli cell that has been transformed with the N. meningitidis lgtA gene, the A. segnis lex-1 gene, and the E. coli pgm, galE, lacY and galU genes, wherein said E. coli cell comprises deletions in the endogenous wcaJ, lacZ, lacA, nagB, waaB, and mdoH genes, and wherein said E. coli cell has been transformed with a porin gene selected from the E. coli ompF gene, the E. coli scrY gene, the K. pneumoniae scrY gene, the E. coli ompC gene, the S. enterica ompA gene, and the S. enterica ompN-ompC genes, and the E. coli cell has been transformed with a saccharide transporter gene selected from the E. coli mdtM gene, the S. lincolnensis lmrC gene, a P. carotovorum gene encoding the protein disclosed in GenBank accession No. ZP_03829909, the G. anatis ydeE gene, a Pseudomonas sp. MT-1 gene encoding the protein disclosed in GenBank accession No. BAP78849, and a Beeauveria bassiana D1-5 gene encoding the protein disclosed in GenBank accession No. KGQ13398, as a working example. The specification also discloses using a heterologous promoter and increasing the copy number of a gene encoding a porin or a saccharide transporter. However, the specification fails to disclose (i) the structural features required in any gene that encodes an enzyme/protein that could be used for the synthesis of any human milk oligosaccharide or the structural features required in any gene encoding any porin or saccharide transporter, (ii) the structure/identity of expression inducers of the desired gene or other genetic modifications that could be made to increase the expression of an endogenous gene, such as structural modifications to promoters, the expression of proteins that could act as enhancers of transcription, antisense molecules to block expression of genes that inhibit the expression of the desired gene, or structural modifications to the coding region of a gene to alter the activity of the protein encoded by the target gene. No structure/function correlation has been provided that would allow one of skill in the art to recognize those genes that encode the enzymes required to produce any human milk oligosaccharide in any gram-negative cell. No structure/function correlation has been provided that would allow one of skill in the art to recognize those genes that encode any porin or saccharide transporter, or the genetic modifications required in any gram-negative cell to produce the desired oligosaccharide.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The amino acid sequence of a protein determines the function of such protein. Neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of any protein (or its gene) that could be used to synthesize any human milk oligosaccharide, or the structure of any porin or saccharide transporter as required by the claims. In addition, the art does not provide any teaching or guidance as to which genetic modifications can be made to any gram-negative bacterial cell so that the bacterial cell can synthesize the desired oligosaccharides. The art provides no guidance as to any additional methods to deregulate the expression of an endogenous gene that do not require some knowledge or guidance as to the structural features of the gene to be deregulated.
While the argument can be made that the structure/identity of those proteins and their corresponding genes can be obtained by structural homology, the art clearly teaches that (i) there is a high level of unpredictability associated with accurate functional annotation of proteins based solely on structural homology, and (ii) modification of a protein’s amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are tolerant of modification and which ones are conserved is highly unpredictable. For example, Singh et al. (Current Protein and Peptide Science 19(1):5-15, 2018) disclose different protein engineering approaches and state 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 (page 11, left column, last paragraph). Sadowski et al. (Current Opinion in Structural Biology 19:357-362, 2009) teach that much of the problem in assigning function from structure comes from functional convergence, where although a stable structure is required to perform many functions it is not always necessary to adopt a particular structure to carry out a particular function (page 357, right column, first full paragraph). Sadowski et al. further explain that the unexpected and significant difficulties of predicting function from structure show that the potential of structural models for providing novel functional annotations has not yet fully realized. Sadowski et al. also states that while a few successes have been achieved which required manual intervention, the ability to vary the requirements for specificity in prediction means that it is difficult to determine how useful the end result may be for the user (page 361, left column, first full paragraph). The teachings of Singh et al. and Sadowski et al. are further supported by the teachings of Witkowski et al., Tang et al. and Seffernick et al. already discussed above, where it is shown that even small amino acid changes result in enzymatic activity changes.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of isolating polypeptides and genes were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an infinite number of proteins/genes and determine which ones have the desired activity or encode a protein with the desired activity. Similarly, it was not routine in the art to screen by a trial and error process for an infinite number of genetic modifications to deregulate expression of a desired gene, proteins that can act as expression regulators, or antisense molecules that could block expression of genes that encode repressors of the expression of the desired gene. In the absence of (a) a rational and predictable scheme for identifying which proteins and their genes are more likely to have the desired activity, (b) a correlation between structure and activity, (c) a rational and predictable scheme for identifying those genetic modifications most likely to result in any gram-negative bacterial cell to produce a human milk oligosaccharide, and (d) some knowledge or guidance as to which genetic modifications can result in deregulation of the desired gene, one of skill in the art would have to test an essentially infinite number of proteins, nucleic acids, and modifications to determine which genetic modifications would lead to the desired outcome, and which proteins have the desired activity.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and function, and the high degree of unpredictability of the prior art in regard to function determination based on structural homology, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Claim Rejections - 35 USC § 102 (AIA )
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8-14 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Samain et al. (WO 2015/197082 published 12/30/2015; cited in the IDS).
Claims 8-14 are directed in part to a method for producing a human milk oligosaccharide by (a) culturing a gram-negative bacterial cell, wherein said bacterial cell is able to produce the human milk oligosaccharide, wherein said bacterial cell produces a saccharide transporter which is located in its inner membrane and a porin which is located in its outer membrane, and (b) recovering the human milk oligosaccharide from the culture medium. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Samain et al. teach the production of LNnT (lacto-N-neotetraose; a human milk oligosaccharide) by culturing an E. coli cell that has been genetically modified to produce LNnT and has been transformed with a plasmid to express a sucrose porin and a sucrose transporter encoded by the scrY and scrA genes, respectively (page 27, line 21-page 28,line 23, Example 1). Samain et al. teach the production of 2’-FL (2-fucosyllactose; a human milk oligosaccharide) by culturing an E. coli cell that has been genetically modified to produce 2’-FL and has been transformed with a plasmid to express a sucrose porin and a sucrose transporter encoded by the scrY and scrA genes, respectively (page 28, line 23-page 29 ,line 17, Example 2). As known in the art and also admitted in the specification, E. coli is a gram-negative bacterial cell that comprises a cytoplasm, an inner membrane, an outer membrane and a periplasmic space between the inner membrane and the outer membrane. Samain et al. teach that a porin encoded by the scrY gene facilitates sucrose diffusion through the outer membrane and a sucrose transport protein encoded by the scrA gene is located on the cell membrane (also known as inner membrane; page 24, lines 10-14). Samain et al. teach recovering the oligosaccharide from the culture medium (page 30, lines 12-14, claim 1). Therefore, the teachings of Samain et al. anticipate the instant claims as written/interpreted.
Claims 8-14 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Jennewein et al. (WO 2017/042382 published 3/16/2017; cited in the IDS) as evidenced by Hardesty et al. (Journal of Bacteriology 173(2):449-456, 1991).
Claims 8-14 are directed in part to a method for producing a human milk oligosaccharide by (a) culturing a gram-negative bacterial cell, wherein said bacterial cell is able to produce the human milk oligosaccharide, wherein said bacterial cell produces a saccharide transporter which is located in its inner membrane and a porin which is located in its outer membrane, and (b) recovering the human milk oligosaccharide from the culture medium. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Jennewein et al. teach the production of several human milk oligosaccharides by culturing E. coli cells that have been genetically modified to produce said oligosaccharides (pages 21-32) including lacto N-triose II (LNT-2; Example 3, page 39, claim 3), lacto-N-tetraose (LNT; Example 6; page 39, claim 3) and lacto-N-neotetraose (LNnT; page 27, paragraph [0118]; page 39, claim 3). Jennewein et al. teach that their E. coli cells have been genetically modified by introducing plasmids to express sugar efflux transporters such as the protein encoded by the yjhB gene, and SET proteins from E. coli as well as the protein encoded by the M. succiniciproducens proP gene and the C. neteri setA gene (page 24, Example 3; page 32, Example 8, paragraph [0141]; page 41, claim 9). Jennewein et al. teach that their E. coli cells have been genetically modified by introducing plasmids to express 66 sugar efflux transporters including the protein encoded by the yebQ, yabM, bcr, ydeA, proP2, setA, fucP, mdeA, and lmrA genes (Example 7, paragraphs [00136]- [00138]). Jennewein et al. teach recovery of the oligosaccharide from the culture medium (page 39, claim 1). As known in the art and also admitted in the specification, E. coli is a gram-negative bacterial cell that comprises a cytoplasm, an inner membrane, an outer membrane and a periplasmic space between the inner membrane and the outer membrane. As evidenced by Hardesty et al., E. coli has an endogenous gene, scrY that encodes a porin that is located in the outer membrane (page 454, right column, last 11 lines). Therefore, the teachings of Jennewein et al. anticipate the instant claims as written/interpreted.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 8-14 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 8,652,808 as evidenced by Hardesty et al. (Journal of Bacteriology 173(2):449-456, 1991). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 8-14 of the instant application are directed in part to a method for producing a human milk oligosaccharide by (a) culturing a gram-negative bacterial cell, wherein said bacterial cell is able to produce the human milk oligosaccharide, wherein said bacterial cell produces a saccharide transporter which is located in its inner membrane and a porin which is located in its outer membrane, and (b) recovering the human milk oligosaccharide from the culture medium. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 1-10 of U.S. Patent No. 8,652,808 are directed in part to a method for the production of fucosyllactose, comprising the steps of: a) providing an E. coli bacterial cell transformed to comprise at least one nucleic acid sequence coding for a fucosyltransferase, and transformed to comprise at least one nucleic acid sequence coding for a protein of the sugar efflux transporter (SET) family, wherein the protein of the SET family is a SetA protein, b) culturing the E. coli bacterial cell in a medium under conditions permissive for the production of fucosyllactose, whereby the fucosyllactose is exported into the medium; and c) extracting said fucosyllactose from the medium. As known in the art and also admitted in the specification, E. coli is a gram-negative bacterial cell that comprises a cytoplasm, an inner membrane, an outer membrane and a periplasmic space between the inner membrane and the outer membrane. As evidenced by Hardesty et al., E. coli has an endogenous gene, scrY, that encodes a porin that is located in the outer membrane (page 454, right column, last 11 lines). Therefore, the method of claims 8-14 of the instant application is anticipated by the method of claims 1-10 of U.S. Patent No. 8,652,808 as written/interpreted.
Claims 8-14 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 23 of copending Application No. 17/434,967 as evidenced by Hardesty et al. (Journal of Bacteriology 173(2):449-456, 1991). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 8-14 of the instant application are directed in part to a method for producing a human milk oligosaccharide by (a) culturing a gram-negative bacterial cell, wherein said bacterial cell is able to produce the human milk oligosaccharide, wherein said bacterial cell produces a saccharide transporter which is located in its inner membrane and a porin which is located in its outer membrane, and (b) recovering the human milk oligosaccharide from the culture medium. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claim 23 of copending Application No. 17/434,967 is directed in part to a method for producing a carbohydrate of interest, wherein said method requires (a) culturing a microorganism that is genetically engineered to produce said carbohydrate of interest, wherein said microorganism further comprises at least one exporter protein or permease to export the carbohydrate of interest from the cell, and (b) recovering the carbohydrate of interest. The specification of copending Application No. 17/434,967 as evidenced by claim 14, discloses several human milk oligosaccharides including lacto-N-neotetraose, as preferred embodiments of the genus of carbohydrates of interest recited in the claim. The specification of copending Application No. 17/434,967 also discloses E. coli as one of the preferred embodiments of the genus of microorganisms required by the method claimed and a porin as a preferred embodiment of the genus of exporter proteins required by the microorganism. As known in the art and also admitted in the specification, E. coli is a gram-negative bacterial cell that comprises a cytoplasm, an inner membrane, an outer membrane and a periplasmic space between the inner membrane and the outer membrane. As evidenced by Hardesty et al., E. coli has an endogenous gene, scrY, that encodes a porin that is located in the outer membrane (page 454, right column, last 11 lines). Therefore, the method of claims 8-14 of the instant application is deemed an obvious variation of the method of claim 23 of copending Application No. 17/434,967 in view of the preferred embodiments disclosed.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
February 18, 2026