Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Application Status
This application is a 371 of PCT/KR2021/020000, filed on 06/20/2023.
Claims 12-28 are currently pending in the instant application.
The preliminary amendment filed on 01/19/2026, amending claims 12, 20, canceling claims 1-11, and adding new claims 21-28 is acknowledged.
Election/Restriction
Applicant's election with traverse of Group II, Claims 12-19, drawn to a recombinant Bacillus sp. microorganism, comprising an α-1,2-fucosyltransferase gene, or transformed with a vector comprising the expression cassette comprising an α-1,2-fucosyltransferase gene in the response filed on 01/19/2026 is acknowledged.
Argument: Applicants argue that the instant specification repeatedly identifies the inventive contribution as engineering Bacillus with an α-1,2-fucosyltransferase expression cassette in which expression is driven by a constitutive promoter, to improve production of 2'-fucosyllactose (including disclosure that constitutive promoters improve productivity relative to inducible promoters). Consistent with that disclosure, Claim 12 (Group II) requires a recombinant Bacillus sp. microorganism comprising a gene expression cassette expressing a-1,2-fucosyltransferase and a regulatory sequence comprising a constitutive expression promoter. Claims 15 and 16 (Group III features) depend from Claim 12 (directly or indirectly) and therefore necessarily include the same limitations of Claim 12 i.e., the microorganism includes the a-1,2-fucosyltransferase cassette under a constitutive promoter-and then further require a fucose synthesis gene expression cassette (optionally on the same vector or a second vector) as an additional refinement. Accordingly, Groups II and III are not "unrelated" inventions: they are technically linked by the same special technical feature, namely: A recombinant Bacillus sp. microorganism comprising an a-1,2-fucosyltransferase expression cassette operably linked to a constitutive expression promoter.
Response: Since, the elected claims of Group II are drawn to Bacillus Sp., of microorganism (product), the Examiner is combining claims 15 and 16 of Group III with elected Group II, and claim 20, which is drawn to a method of use of the microorganism of Group II, is now placed in a new Group IV.
Applicants arguments have been fully considered, but are not deemed persuasive about restriction requirement because: The inventions listed in the claims filed after Restriction requirement as Groups II – III and IV (claim 20) do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: Recombinant Bacillus sp. microorganisms of Group, II-III, and a method for producing 2'-fucosyllactose, comprising a step of culturing a-the recombinant Bacillus sp., of claim 12 of Group IV, are each unrelated and chemically distinct entities. The only shared technical feature of these groups is that they all relate to a recombinant Bacillus sp. microorganism, comprising an α-1,2-fucosyltransferase gene, or transformed with a vector comprising the expression cassette comprising an α-1,2-fucosyltransferase gene. However, this shared technical feature is not a “special technical feature” as defined by PCT Rule 13.2 as it does not define a contribution over the art. McCoy et al. (US 2017/0081353A, publication 03/23/2017, see, 102 rejection, IDS) teach a Alpha (1,2) Fucosyl-transferase syngenes for use in the Production of Fucosylated Oligosaccharides, and further teach a compositions and methods for engineering Bacillus subtilis, E.coli or other host production bacterial strains (see, claims 28-29) to produce fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection, and said bacterium comprising an isolated nucleic acid encoding a lactose-accepting α (1,2) fucosyltransferases enzyme in an expression plasmid vector pG217 under heterologous constitutive strong promoter LacIq (para 11, 15, 73, Fig. 11-12 ), wherein said α(1,2) fucosyltransferases enzyme comprises Lachnospiraceae sp. FutQ, Tannerella sp. FutS, Clostridium bolteae+13 FutP, Salmonella enterica FutZ, Methanosphaerula palustries FutR, Akkermansia muciniphilia FutY, Clostridium bolteae FutP, or a functional variant or fragment thereof, wherein said bacterium is Escherichia coli. Thus, a recombinant Bacillus sp. microorganism, comprising an α-1,2-fucosyltransferase gene does not make contribution over the prior art and lack unity of invention. Besides, 37 CFR 1.475 does not provide for multiple products and/or methods within a single application. Therefore, inventions of Group II - IV lack unity of invention.
However, new claims 21-28 will be examined with elected Group II and III.
Claims 20 (method claim) is 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. However, claim 20 will be rejoined when claims of Group II and III are allowable.
The examiner has required restriction between product and process claims. Where applicant elects claims directed to the product, and a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, Applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to rejoinder.
The requirement is still deemed proper and is therefore made FINAL.
Claims 12-18, 19, and 21-28 are present for examination.
Priority
Acknowledgement is made of applicants claim for foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application 10-2020-0189491, (Republic of Korea) filed on 12/13/2020 without English translation.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 06/20/2023, 08/02/2024, and 01/16/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner. The signed copies of 1449 are enclosed herewith.
Drawings
Drawings submitted on 06/20/2023 are accepted by the Examiner.
Claim Objections
Claim 16 is objected to in the recitation p3610, p12455, p24930, p0706, pTu and pPDC”; as abbreviations should not be used without at least once fully setting forth what they are used for. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 19 is rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. In the present instance, claim 19 recite “culture.” The metes and bounds of the term “culture.” are not clear to the Examiner. It is not clear whether something is missing after the phrase “culture.” , which could be “culture medium, or something else”, which are unknown, rendering the Metes and Bounds of the term unclear and confusing. Clarification is required.
Claims 17 and 28 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claims 17 and 28 are indefinite in the recitation of figures in the claim (see, FIG. 1b) which renders the claims indefinite and not permitted at all unless a special circumstances. Thus, FIG. 1b would not be considered as claim limitation for art rejection. Clarification and correction is required.
See MPEP 2173.05(s), which states:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).”
Claim Rejections - 35 USC § 112(a)
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.
A. Written Description
Claims 12-18, 19, 21-22, and 24-28 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, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 12 is directed to a recombinant Bacillus sp. microorganism, comprising a gene expression cassette expressing α-1,2- fucosyl transferase, or transformed with a vector comprising the expression cassette, wherein the gene expression cassette comprises a nucleic acid sequence encoding α-1,2-fucosyl transferase, and a regulatory sequence operably linked thereto, and wherein the regulatory sequence comprises a constitutive expression promoter.
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.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).
Thus, Claim 12 is drawn to a recombinant Bacillus sp. microorganism, comprising any gene encoding any α-1,2-fucosyl transferase enzyme derived from any sources having no structural feature for expression, and cloned in an expression cassette (contemplating in a plasmid or vector), or transformed with a vector comprising the expression cassette, wherein the gene expression cassette comprises any nucleic acid sequence encoding any α-1,2-fucosyl transferase enzyme derived from any sources having no structural feature for expression, and any regulatory sequence operably linked thereto, and wherein the regulatory sequence comprises any constitutive expression promoter, and the α-1,2-fucosyl transferase enzymes encompasses many α-1,2-fucosyl transferase enzymes, and many mutants, variants and fragments thereof, which can have wide variety of unknown structures, i.e. No Structure-Function correlation, which is required to fulfill the Written Description (WD) requirement.
As discussed in the written description guidelines 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. 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.
Furthermore, the genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides are adequately described by the disclosure of the structures of prior art. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer, it is difficult to state criteria for successful prediction of function, since function is a vague concept. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Claims are drawn to very broadly any nucleic acid sequence encoding any α-1,2-fucosyl transferase enzyme derived from any sources having no structural feature for expression and that encompasses many α-1,2-fucosyl transferase enzyme derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of α-1,2-fucosyl transferase enzymes has been provided, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the α-1,2-fucosyl transferase enzymes, within the scope of the claimed genus. The genus of polypeptides claimed is a large variable genus including many mutants, variant and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated enzymes (α-1,2-fucosyl transferase) within the scope of these claims. The specification discloses the structure of only few representative species of the claimed genus, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed genus. Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim Rejections - 35 USC § 102
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.
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.
MPEP-2131 Anticipation — Application of 35 U.S.C. 102 [R-08.2017]
A claimed invention may be rejected under 35 U.S.C. 102 when the invention is anticipated (or is "not novel") over a disclosure that is available as prior art. To reject a claim as anticipated by a reference, the disclosure must teach every element required by the claim under its broadest reasonable interpretation. See, e.g., MPEP § 2114, subsections II and IV.
"A claim is anticipated only if each and every element as set forth in the claim is found, either expressly or inherently described, in a single prior art reference." Verdegaal Bros. v. Union Oil Co. of California, 814 F.2d 628, 631, 2 USPQ2d 1051, 1053 (Fed. Cir. 1987). "When a claim covers several structures or compositions, either generically or as alternatives, the claim is deemed anticipated if any of the structures or compositions within the scope of the claim is known in the prior art." Brown v. 3M, 265 F.3d 1349, 1351, 60 USPQ2d 1375, 1376 (Fed. Cir. 2001) Note that, in some circumstances, it is permissible to use multiple references in a 35 U.S.C. 102 rejection. See MPEP § 2131.01.
MPEP-2131.01 Multiple Reference 35 U.S.C. 102 Rejections [R-11.2013]
Normally, only one reference should be used in making a rejection under 35 U.S.C. 102. However, a 35 U.S.C. 102 rejection over multiple references has been held to be proper when the extra references are cited to:
(A) Prove the primary reference contains an "enabled disclosure;"
(B) Explain the meaning of a term used in the primary reference; or
(C) Show that a characteristic not disclosed in the reference is inherent.
Claims 12-15, 17-18, 19, 25-26 and 28 are rejected under 35 U.S.C. 102(a)(1) based upon a public use or sale or other public availability of the invention as anticipated by McCoy et al. (Alpha (1,2) Fucosyl-transferase syngenes for use in the Production of Fucosylated Oligosaccharides. US 2017/0081353A, publication 03/23/2017, see IDS).
The Broadest Reasonable Interpretation (BRI) of claim 12, which is drawn to a recombinant Bacillus sp. microorganism, comprising any gene encoding any α-1,2-fucosyl transferase enzyme derived from any sources having no structural feature for expression, and cloned in an expression cassette, or transformed with a vector comprising the expression cassette, wherein the gene expression cassette comprises any nucleic acid sequence encoding any α-1,2-fucosyl transferase enzyme derived from any sources having no structural feature for expression, and any regulatory sequence operably linked thereto, and wherein the regulatory sequence comprises any constitutive expression promoter, i.e. any α-1,2-fucosyl transferase enzyme having structure, which, encompasses many α-1,2-fucosyl transferase enzymes, and many mutants, variants and fragments thereof, which can have wide variety of unknown structures.
Regarding claims 12-15, 17-18, 19, 25-26 and 28, McCoy et al. teach (Alpha (1,2) Fucosyl-transferase syngenes for use in the production of fucosylated Oligosaccharides, and further teach a compositions and methods for engineering Bacillus subtilis, E.coli or other host production bacterial strains (see, claims 28-29) to produce fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection, and an isolated bacterium comprising an isolated nucleic acid encoding a lactose-accepting α (1,2) fucosyltransferases enzyme in an expression plasmid vector pG217 under heterologous constitutive strong promoter LacIq (para 11, 15, 73, Fig. 11-12 ), wherein said α(1,2) fucosyltransferases enzyme comprises Lachnospiraceae sp. FutQ, Tannerella sp. FutS, Clostridium bolteae+13 FutP, Salmonella enterica FutZ, Methanosphaerula palustries FutR, Akkermansia muciniphilia FutY, Clostridium bolteae FutP, or a functional variant or fragment thereof, wherein said bacterium is Escherichia coli, wherein said bacterium further comprises reduced level of β-galactosidase activity, a defective colanic acid synthesis pathway, an inactivated adenosine-5′-triphosphate (ATP)-dependent intracellular protease, an inactivated endogenous lacA gene, well as the bacterium comprises the genotype ΔampC::Ptrp BcI, Δ(lacI-lacZ)::FRT, PlacIqLacY+, ΔwcaJ::FRT, thyA::Tn10, Δlon:(npt3, lacZ+), and upregulation of fucose synthesis pathway genes including LacY encoding lactose permease for lactose transportation, deletion of Δlon gene encoding a protease, wherein the deletion of protease Δlon stabilizes rcsA/B gene, encoding positive regulator of transcription results in the upregulation of gmd (GDP-mannose-4-6-dehydratase), ManA (phosphor-mannose isomerase), ManB (phosphor-mannose mutase), ManC (mannose-1-phosphate guanyl-transferase) and fcl (GDP-fucose synthase) results in the up-regulation of GDP-fucose synthesis through up-regulation of gmd, wherein GDP-Fucose, which is a substrate for the synthesis of 2-Fucosyllactose (see,Fig.2), a Fucosylated oligosaccharide also known as HMO (human milk oligosaccharide) using said α (1,2) fucosyltransferases enzyme (futC) , wherein said purified fucosylated oligosaccharide does not comprise acetyl-lactose that is detectable by thin layer chromatography, wherein produced fucosylated oligosaccharide is in the form of a crystalline powder (see, abstract, para 11, 14, 15, 17, 19-20, 25, 49, 52, 98, Fig. 2, 11-12, and claims 1-56).
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Therefore, McCoy et al. anticipate claims 12-15, 17-18, 19, 25-26 and 28 of the instant application as written.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
According to MPEP 2143:
“Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield
predictable results;
(B) Simple substitution of one known element for another to obtain predictable
results;
(C) Use of known technique to improve similar devices (methods, or products)
in the same way;
(D) Applying a known technique to a known device (method, or product) ready
for improvement to yield predictable results;
(E) “ Obvious to try ” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in
either the same field or a different one based on design incentives or other market
forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art
reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.”
Claims 12-15, 16, 17-18, 19, 21, 25-26, 27 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over McCoy et al. (Alpha (1,2) Fucosyl-transferase syngenes for use in the Production of Fucosylated Oligosaccharides. US 2017/0081353A, publication 03/23/2017, see IDS) as applied to Claims 12-15, 17-18, 19, 25-26 and 28 above, and further in view of Hollands et al. (Increasing export of 2' fucosyllactose from microbial cells through the expression of a heterologous nucleic acid. WO 2019/209241A1, publication 10/31/2019, claim benefit of PCT filing date 04/23/2018).
Regarding claims 12-15, 17-18, 19, 21, 25-26, 27 and 28, McCoy et al. teach (Alpha (1,2) Fucosyl-transferase syngenes for use in the production of fucosylated Oligosaccharides, and further teach a compositions and methods for engineering Bacillus subtilis, E.coli or other host production bacterial strains (see, claims 28-29) to produce fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection, and an isolated bacterium comprising an isolated nucleic acid encoding a lactose-accepting α (1,2) fucosyltransferases enzyme in an expression plasmid vector pG217 under heterologous constitutive strong promoter LacIq (para 11, 15, 73, Fig. 11-12 ), wherein said α(1,2) fucosyltransferases enzyme comprises Lachnospiraceae sp. FutQ, Tannerella sp. FutS, Clostridium bolteae+13 FutP, Salmonella enterica FutZ, Methanosphaerula palustries FutR, Akkermansia muciniphilia FutY, Clostridium bolteae FutP, or a functional variant or fragment thereof, wherein said bacterium is Escherichia coli, wherein said bacterium further comprises reduced level of β-galactosidase activity, a defective colanic acid synthesis pathway, an inactivated adenosine-5′-triphosphate (ATP)-dependent intracellular protease, an inactivated endogenous lacA gene, well as the bacterium comprises the genotype ΔampC::Ptrp BcI, Δ(lacI-lacZ)::FRT, PlacIqLacY+, ΔwcaJ::FRT, thyA::Tn10, Δlon:(npt3, lacZ+), wherein the vector comprises alpha-(1,2)-FT that comprises ribosomal binding site (RBS) sequence and upregulation of fucose synthesis pathway genes including LacY encoding lactose permease for lactose transportation, deletion of Δlon gene encoding a protease, wherein the deletion of protease Δlon stabilizes rcsA/B gene, encoding positive regulator of transcription results in the upregulation of gmd (GDP-mannose-4-6-dehydratase), ManA (phosphor-mannose isomerase), ManB (phosphor-mannose mutase), ManC (mannose-1-phosphate guanyl-transferase) and fcl (GDP-fucose synthase) results in the up-regulation of GDP-fucose synthesis through up-regulation of gmd, wherein GDP-Fucose, which is a substrate for the synthesis of 2-Fucosyllactose (see,Fig.2), a Fucosylated oligosaccharide also known as HMO (human milk oligosaccharide) using said α (1,2) fucosyltransferases enzyme (futC) , wherein said purified fucosylated oligosaccharide does not comprise acetyl-lactose that is detectable by thin layer chromatography, wherein produced fucosylated oligosaccharide is in the form of a crystalline powder (see, abstract, para 9, 11, 14, 15, 17, 19-20, 25, 49, 52, 80, 98, 136, Fig. 2, 11-12, 14 and claims 1-56).
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McCoy et al. do not teach using constitutive promoter such as PDC1 (for claims 16 and 21) for expressing fucose synthesis genes recited in claim 15 for expression.
However, Holland et al. teach increasing export of 2' fucosyl-lactose (HMO) from microbial cells through the expression of a heterologous nucleic acid, and further teach microbial cells genetically engineered with a heterologous nucleic acid sequence that increases export of 2' fucosyl-lactose by expression of gmd gene (GDP-mannose-4-6-dehydratase), which is cloned in a vector under constitutive pyruvate decarboxylase (PDC1) promoter (see, abstract, pg9, 19, para 2, pg35, para 2, and claims 1, 15, 17, 22. Fig. 1).
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the claimed invention as a whole at the time of the invention was made by combining the teachings of McCoy et al. and Hollands et al. to use strong PDC promoter to express genes including gmd in order to increased expression and production of 2' fucosyl-lactose (HMO) to arrive the claimed invention.
One of ordinary skilled in the art would have been motivated to overexpress gmd gene (GDP-mannose-4-6-dehydratase) to increase export and production of 2' fucosyl-lactose (HMO), which is nutritionally, pharmaceutically and clinically and financially beneficial.
One of ordinary skilled in the art would have a reasonable expectation of success because McCoy et al. and Hollands et al. could successfully produce 2' fucosyl-lactose (HMO) in an engineered host cell expressing said genes.
Thus, the above references render the claims prima facie obvious to one of ordinary skill in the art.
Double Patenting Rejections (Provisional)
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b
Claims 12-15, 17-18, 23, 25, and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8 and 9 of co-pending Application No. 18/270,293 (US2025/0346912A1, publication 11/13/2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are of overlapping scope.
Claims 12-15, 17-18, 23, 25, and 26 of the instant application are drawn to a recombinant Bacillus sp. microorganism, comprising a gene expression cassette expressing a-1,2-fucosyl transferase or transformed with a vector comprising the expression cassette, wherein the gene expression cassette comprises a nucleic acid sequence encoding a-1,2- fucosyl transferase, and a regulatory sequence operably linked thereto, and wherein the regulatory sequence comprises a constitutive expression promoter, wherein the vector further comprises a fucose synthesis gene expression cassette, wherein the microorganism further comprises a vector comprising a fucose synthesis gene expression cassette, wherein the vector further comprises a fucose synthesis gene expression cassette, or the microorganism further comprises a vector comprising a fucose synthesis gene expression cassette, wherein the fucose synthesis gene expression cassette comprises at least one selected from the group consisting of a nucleic acid sequence encoding GTP mannose-l-phosphate guanylyl transferase, a nucleic acid sequence encoding phosphor-mannomutase, a nucleic acid sequence encoding GDP-L-fucose synthase (WcaG), and a nucleic acid sequence encoding GDP-D-mannose-4,6-dehydradase, and a regulatory sequence operably linked thereto, wherein the regulatory sequence comprises a constitutive expression promoter, wherein the vector comprising a fucose synthesis gene expression cassette is a recombinant vector, wherein the Bacillus sp. microorganism is at least one selected from the group consisting of Bacillus megaterium, Bacillus subtilis, Bacillus cereus, Bacillus licheniformis, Bacillus amyloliquefaciens, and Bacillus thuringiensis, wherein the nucleic acid sequence encoding a-1,2-fucosyl transferase comprises a nucleic acid sequence encoding at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5, wherein the gene expression cassette further comprises a nucleic acid sequence encoding a lactose membrane transport protein, wherein the lactose membrane transport protein is at least one selected from the group consisting of Lac12 and LacY.
The claims 1, 3-8 and 9 of the co-pending application are drawn to a recombinant microorganism, transformed to express a-1,2-fucosyltransferase comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5, wherein the recombinant microorganism is Bacillus sp. microorganism, Corynebacterium sp. microorganism, Escherichia sp. microorganism, or yeast, wherein the Bacillus sp. microorganism is Bacillus megaterium, Bacillus subtilis, Bacillus cereus, Bacillus coagulans, Bacillus licheniformis, or Bacillus stearothermophilus, the Corynebacterium sp. microorganism is Corynebacterium glutamicum, the Escherichia sp. microorganism is Escherichia coli, and the yeast is Saccharomyces cerevisiae, or Candida utilis, wherein the microorganism does not have 2'-fucosyllactose productivity before recombination, and obtain 2'- fucosyllactose productivity by recombination, wherein the recombinant microorganism expresses a fucose synthesis gene, at least one selected from the group consisting of GDP-D-mannose-4,6- dehydratase, GDP-L-fucose synthase, phosphomannomutase, and GTP-mannose-1-phosphate guanylyltransferase, wherein the recombinant microorganism expresses a lactose membrane transport protein, wherein the lactose membrane transport protein is at least one selected from the group consisting of Lac12 and LacY.
The above indicated claims 1, 3-8 and 9 of the reference patents while not totally identical to the instant claims, are indeed a product claim of a recombinant microorganism, transformed to express a-1,2-fucosyltransferase comprising at least one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5 as claimed in the instant claims. The portion of the claims and the specification in the reference co-pending application, while drawn to the actual product as claims in the instant application, includes several embodiments that would anticipate the invention claimed in the instant application. Claims of the instant application listed above cannot be considered patentably distinct over claims of the reference patents when there are specifically recited embodiments that would either anticipate to claims 12-15, 17-18, 23, 25, and 26 of the instant application or alternatively render them obvious. Alternatively, claims 12-15, 17-18, 23, 25, and 26 cannot be considered patentably distinct over claims of the reference patent US 9957530 B2 when there is specifically disclosed embodiment in the reference patent that falls within the scope of claims 12-15, 17-18, 23, 25, and 26 of the instant application, i.e. there is substantially overlapping scope between the claimed invention and the teachings of the reference. One having ordinary skill in the art would have been motivated to do this because that embodiment is disclosed as being a preferred embodiment within the claims 1, 3-8 and 9 of US patent1, 3-8 and 9.
One having ordinary skill in the art would have been motivated to do this because that embodiment is disclosed as being a preferred embodiment within the claims 1, 3-8 and of copending Application No. co-pending Application No. 18/270,293 (US2025/0346912A1, publication 11/13/2025).
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
Status of the claims:
Claims 22, and 24 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 12-15, 16, 17-18, 19, 21, 23 (ODP only), 25-26, 27, and 28 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, PhD.
Primary Patent Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656
Prosecution Insights