DETAILED ACTION
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 .
Election/Restrictions
Applicant's species election with traverse of a method for the production of fucosylated oligosaccharides using a genetically modified host cell comprising the following species, ManA as a gene to be overexpressed, encoding an enzyme that catalyzes the isomerization of fructose-6-phosphate to mannose-phosphate in the de novo synthesis of GDP-fucose and wbgL as an exogenous gene encoding alpha-1,2-fucosyltransferase, and species further including yberc001_9420 as a gene that enables or facilitates the export of the fucosylated oligosaccharide and E. coli LacY as a gene encoding a lactose permease in the reply filed on September 18, 2025 is acknowledged. Applicants state claims 26-30 and 32-46 read on the elected species. The traversal is on the ground(s) that each of the species possess a commonality of design, operation, or effect and are therefore not independent, but are inter-related. Specifically, all species of the group identified as enzymes necessary for the de novo synthesis of GDP-fucose are active in such synthesis process. Additionally, all species identified as genes encoding alpha-1,2-fucosyltransferase or alpha-1,3-fucosyltransferase (not elected) are genes encoding fucosyltransferases, which are described in the specification as enzymes that transfer an L-fucose sugar from a GDP-fucose donor substrate to an acceptor substrate to form a fucosylated oligosaccharide. This is not found persuasive because the species are each independent chemical structures with different activities, such as enzymatic kinetics, and substrate affinities.
The requirement is still deemed proper and is therefore made FINAL.
Claims 31 and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on September 18, 2025.
Claims 26-30 and 32-46, drawn to the elected species are currently under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The priority date is October 29, 2016.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on December 21, 2023 and March 7, 2025 are being considered by the examiner. The signed IDS forms are attached with the instant office action.
Drawings
The drawings are objected to because in figure 3 the reference to SeqID 5 is not like the identifier SEQ ID NO:5. Suggest using the standard format, SEQ ID NO: as the identifier for sequence set forth in the sequence listing. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 29, 30, 37, and 45 are objected to because of the following informalities:
Claim 30 has is a typographical error on the second line. There is a space missing between the two words ---or fucT2---.
Claims 29 and 37 are objected to because they fail to refer back to another claim as disclosed by 37 CFR 1.75 (c). Suggest, new claims that are numbered after the claim from which they depend, for example in the text of claim 29 should appear after claim 44 as it depends from claim 44.
Claim 45 is objected to because there is a typographical error. The 3rd line has an extra space between “fructose-6- phosphate-converting enzyme” and between line 4 and 5 the word “fructose-6-phosphate converting enzyme” is missing a dash between the words phosphate and converting.
Appropriate correction is required.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 26-30 and 32-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,898,185 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are of overlapping scope. The claims of the issued patent are drawn to a method for the production of fucosylated oligosaccharides using a genetically modified prokaryotic host cell, the method comprising: providing a prokaryotic host cell which has been genetically modified to have: (i) reduced or abolished activity of a fructose-6-phosphate-converting enzyme as compared to the activity in an unmodified prokaryotic host cell, wherein the fructose-6-phosphate converting enzyme is selected from the group consisting of phosphofructokinase, glucose-6-phosphate isomerase, fructose-6-phosphate aldolase, a transketolase, and a transaldolase; (ii) overexpression of at least one gene encoding an enzyme necessary for the de novo synthesis of GDP-fucose, wherein said at least one gene encoding an enzyme necessary for the de novo synthesis of GDP-fucose is a phosphomannomutase encoding gene, a mannose-1-phosphate guanosyltransferase encoding gene, a GDP-mannose-4,6-dehydratase encoding gene, or a GDP-L-fucose synthase encoding gene; and (iii) expression of an exogenous gene encoding an alpha-1,2-fucosyltransferase and/or an alpha-1,3-fucosyltransferase; and cultivating said genetically modified prokaryotic host cell in a cultivation medium comprising at least one carbon and/or energy source selected from one or more of the group consisting of glycerol, succinate, malate, pyruvate, lactate, ethanol, and citrate; and adding lactose to the cultivation medium; wherein the fucosylated oligosaccharide is obtained from the medium in which the host cell is cultivated; and wherein said genetically modified prokaryotic host cell has an intracellular pool of fructose-6-phosphate that is increased by increasing the activity of a fructose-1,6-bisphosphate phosphatase. The fucosylated oligosaccharide is selected from the group consisting of 2′-fucosyllactose, 3-fucosyllactose or difucosyllactose. The prokaryotic host cell is selected from the group consisting of bacterial cells from an Escherichia coli strain, a Lactobacillus species or a Corynebacterium glutamicum strain. The phosphomannomutase encoding gene is manB, the mannose-1-phosphate guanosyltransferase encoding gene is manC, the GDP-mannose-4,6-dehydratase encoding gene is gmd, and/or the GDP-L-fucose synthase encoding gene is wcaG. The gene encoding the alpha-1,2-fucosyltransferase is wbgL from E. coli O126 or fucT2 from Helicobacter pylori. The host cell is further genetically modified to express a gene encoding a protein which enables or facilitates the export of a fucosylated oligosaccharide into the culture medium. The host cell is further genetically modified to overexpress an endogenous or exogenous permease for the import of lactose. The gene encoding a protein which enables or facilitates the export of the desired fucosylated oligosaccharide is a sugar efflux transporter selected from the group consisting of yberc0001_9420 and setA. The fructose-1,6-bisphosphate phosphatase is encoded by a gene which is a functional active variant of the fructose-1,6-bisphosphate phosphatase (fbpase) from Pisum sativum. The lactose permease is E. coli LacY. The lactose is added from the beginning of the cultivating in a concentration of at least 5 mM, optionally in a concentration of 30, 40, 50, 60, 70, 80, 90, 100, 150 mM, optionally in a concentration >300 mM. Providing of lactose is accomplished by adding lactose to the cultivation medium in a concentration, such that throughout the production phase of the cultivation a lactose concentration of at least 5 mM. The modified genes are integrated into the genome of the host strain. The host cells are cultivated for at least about 60, 80, 100, or about 120 hours or in a continuous manner. The claims are of overlapping methods using similar enzymes with overlapping cultivation medium (see claims 1-18).
Claim Rejections - 35 USC § 112
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 26-30, 32-43, 45, and 46 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are rejected for failing to describe the genus of at least one overexpressed gene encoding an enzyme for the de novo biosynthesis of GDP-fucose that will result in the method of producing a fucosylated oligosaccharide as currently claimed for claim 26 and claims dependent therefrom. Claim 44 is not rejected because it discloses the genes that could be used in the method of production of a fucosylated oligosaccharide.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"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." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163 does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad genus. Claim 26 is broadly generic to all possible genes encoding an enzyme necessary for de novo synthesis of GDP-fucose encompassed by the claims. The possible variations are enormous. Since the MPEP states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. Here, though the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure beyond those disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.") Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANAND U DESAI whose telephone number is (571)272-0947. The examiner can normally be reached 9:30-6:00 EST.
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/ANAND U DESAI/Primary Examiner, Art Unit 1656