DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
2. The information disclosure statement (IDS) submitted on 02/03/23 was filed and entered. The submission is in compliance with the provisions of 37 CFR 1.97 and has been considered by the Examiner.
Election/Restrictions
3. Applicant’s election, without traverse, of Group I, in the reply filed on 10/15/25, is acknowledged.
Claim Status
4. Claims 1-9, 11, 13, 20-23, 25-26, and 29-31 are pending. Claims 10, 12, 14-19, 24, and 27-28 are cancelled. Claims 3-5, 7-8, 11, 13, 20-23, 25, and 29-31 are amended. Claims 30-31 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/15/25. Claims 1-9, 11, 13, 20-23, 25-26, and 29 are under examination.
Specification Objection
5. The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter; See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: With regards to claim 4, The genetically modified microbial cell as in claim 1, wherein the microbial cell is Corynebacterium glutamicum ATCC 13034 is objected to for lack of antecedent basis in the specification because Corynebacterium glutamicum ATCC 13034 is not described in the specification. The closest recitation appears in Tables 1 and 5 but the number is listed as 13032.
Claim Objections
6. Claims 3 and 25 are each objected to because of the following informalities: improper recitation of species names. Latin names of microorganisms are properly recited with the genus name (i.e. first part of binomial identifier) capitalized and species name (i.e. second part of binomial identifier) in lower case, with both in italics, and having the genus name spelled out upon first usage, in order to be understood without requiring reference to the specification (i.e. see MPEP 2173.05(s); claims are to be complete in themselves).
Thus, for example, “E coli” is properly written as “Escherichia coli” upon its first usage and E. coli thereafter (see claim 25, first recitation abbreviated and missing the period). In addition, the genus name for Corynebacterium in claim 3 is misspelled as Corynebacteriun (see “n” as final letter).
Appropriate correction is required.
7. Claims 1, 5, 7, 8, 20, 21, 22, and 25 are each objected to because of the following informalities: improper use of an acronym/abbreviation. Acronyms and abbreviations must be spelled out and/or defined upon first use, in order to be understood without requiring reference to the specification (i.e. see MPEP 2173.05(s); claims are to be complete in themselves); therefore, all gene names must be explained/defined alongside their first recitation. In addition, claim 8 has a misspelling of synthetase (e.g. see line 5; written as synthelase). Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 5, 6, 8, 9, 11, 13, and 20-21 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 the inventor or a joint inventor regards as the invention.
Claim 5 recites the limitation "the pncA gene" in line 2. There is insufficient antecedent basis for this limitation in the claim because there is not recitation of “a pncA gene” in clam 1, from which it directly depends.
The term “variant” in claims 8 and 13 is a relative term which renders the claim indefinite. The term “variant” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In other words, how much variation is required to be included vs. excluded from the limitation and/or how much variation is permitted while still being able to encode for a particular phosphoribosyl pyrophosphate synthetase?
Other dependent claims do not clarify the issues identified above; accordingly, clarification is required to remove scope ambiguity and clearly ascertain the metes and bounds of these claims.
Claim Rejections - 35 USC § 112
10. 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.
11. Claims 1-9, 11, 13, 20-23, 25-26, and 29 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Instant claims are drawn to genetically modified microbial cells capable of producing nicotinamide mononucleotide and/or nicotinamide adenine dinucleotide from nicotinamide, said cell comprising a mutation in one or more endogenous genes selected from the group consisting of cgl1364, cgl1977, cgl2835, iunH1, iunH2, and iunH3, wherein each of said one or more genes codes for a nucleosidase enzyme. Consequently, it is the Office’s position that (1) the independent claim constitutes a "broad generic claim” based on generically claimed microbial cells having as little as one mutation in only one of the genes identified; and (2) the claimed genus has substantial variation because of the numerous options and combinations of options permitted (e.g. mutations, genes and/or microbial cells).
MPEP §2163 states 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 (as in the instant case), the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Further, MPEP §2163 states that the disclosure of only one or two species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In the instant case, the specification provides adequate description for strains of Corynebacterium glutamicum with the capability of producing nicotinamide mononucleotide (NMN) and having an exogenous NadV gene and prsA gene (e.g. see Example 1, 2; Table 5; Figures 5, 6 and 10) identified as:
NMN3 Dcgl1777 Dcgl1778 DpncA Dcgl1963 Dcgl0328;
NMN4 Dcgl1777 Dcgl1778 DpncA Dcgl1963 Dcgl0328 Dcgl2773 DRM DpncA DpncC DushA DpyrE;
NR5 Dcgl1777 Dcgl1778 DpncA Dcgl1963 Dcgl1364 (i.e. iunH3) Dcgl0064 (i.e. pnuC) Dcgl2835 (iunH1) Dcgl1977 (iunH2) DRM DpncA DpncC Dcgl1364 Dcgl1977 Dcgl2835;
NMN11 as NMN4 further modified with a deletion of pgi;
NMN13 as NMN3 further modified with a deletion of pgi;
NMN29 as NMN11 further modified with an insertion of zmZWF.udhA;
NMN30 as NMN13 further modified with an insertion of zmZWF.udhA.
However, the specification does not provide adequate written description for any other genetically modified microbial cells capable of producing nicotinamide mononucleotide (i.e. other than Corynebacterium glutamicum) from nicotinamide (see claim 1). The specification does not provide adequate written description for genetically modified microbial cells, in general (e.g. bacteria, fungi, protists, etc.), or Corynebacterium glutamicum, in particular, capable of producing nicotinamide adenine dinucleotide from nicotinamide (see claim 1). The specification does not provide adequate written description for genetically modified microbial cells, in general, or Corynebacterium glutamicum, in particular, having as little as one mutation in only one of the genes selected from cgl1364, cgl1977, cgl2835, iunH1, iunH2, and/or iunH3 and the ability to produce nicotinamide mononucleotide and/or nicotinamide adenine dinucleotide from nicotinamide (see claims 1-4). It is noted that the mutation is not even required to affect the encoded nucleosidase enzyme (e.g. silent mutations). The specification does not provide adequate written description for genetically modified microbial cells, in general, or Corynebacterium glutamicum, in particular, that do not have an exogenous nadV gene but do have the ability to produce nicotinamide mononucleotide and/or nicotinamide adenine dinucleotide from nicotinamide (see claims 7, 9, and 11). The specification does not provide adequate written description for genetically modified microbial cells, in general, or Corynebacterium glutamicum, in particular, that have less than the genetic modifications of at least NMN3, NMN4 and/or NR5 (see above) and the ability to produce nicotinamide mononucleotide and/or nicotinamide adenine dinucleotide from nicotinamide (see claims 5, 6, 8, 20-23, 25, and 29). The specification does not provide adequate written description for “variants” and/or “mutants” of the prsA gene which encodes a phosphoribosyl pyrophosphate synthetase, in general, a feedback resistant mutant of phosphoribosyl pyrophosphate synthetase, in particular (see claims 8 and 13). With specific regards to claim 4, i.e., a Corynebacterium glutamicum capable of producing nicotinamide mononucleotide and/or nicotinamide adenine dinucleotide from nicotinamide and deposited at ATCC with an accession number of 13034. It is noted that a bacterium having this ATCC accession number is not described in the specification (see Tables 1 and 5 with the number 13032).
Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous options and/or combinations of options of mutations in genes in microbial cells that would predictably produce nicotinamide mononucleotide and/or nicotinamide adenine dinucleotide from nicotinamide have not yet been identified. Accordingly, it is the Office’s position that even one of skill in the art would not accept the disclosure of genetically modified Corynebacterium glutamicum strains found in Table 5; as a sufficient number and/or variety of “representative species” for all of the options and/or combinations of options encompassed by the broad and variable generic claims. Therefore, it is the Office’s position that even one of skill in the art would not conclude that Applicant was in possession of the entire genus.
With regards to the state of the art, microbial production of NMN was still under development and thus necessarily unpredictable, as evidence by the art. For example, Marinescu et al. 2018 (b-nicotinamide mononucleotide (NMN) production in Escherichia coli; Nature Scientific Reports 8:12278; of record) reports the first attempts at biotechnological production methods for microbial production of NMN in bacteria (see Discussion, page 5). Marinescu teaches most bacteria lack phosphoribosyl transferases needed to convert nicotinamide to nicotinamide mononucleotide (NMN; see introduction, page 1). Marinescu teaches E. coli required nicotinamide phosphoribosyl transferase and phosphoribosyl pyrophosphate (PRPP) synthetase to successfully produce NMN in the presence of nicotinamide (NAM) and lactose (e.g. transformed with nadV genes from Haemophilus ducrey and/or Shewanella oneidensis; see Results, pages 2-3; Figure 2; and Table 1). Similarly, Sinclair et al. 2015 (WO 2015/069860) teaches nicotinamide phosphoribosyl transferases are required for the microbial production of NMN in yeast (e.g. see Figure 1).
Therefore, the state of the art does not provide adequate written description support for which options and which combinations of options (i.e. which other mutations in which genes in which microbes) would predictably retain their functional activities of producing NMN from nicotinamide in a genetically engineered cell; thus, the only way to determine if an option works is empirical testing of each and every option.
Consequently, neither the specification nor the state of the art provides sufficient written description to support the genus encompassed by the claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Given the above analysis of the factors as a whole, which the courts have determined are critical in determining whether Applicant is in possession of, or the specification supports, the claimed invention, Applicant has not satisfied the requirements as set forth under 35 U.S.C. 112(a).
Conclusion
12. No claims are allowed at this time.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY MAILLE LYONS whose telephone number is (571)272-2966. The examiner can normally be reached on Monday-Friday 8 am to 5 pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http: //www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Nickol can be reached on (571)-272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
14. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARY MAILLE LYONS/Examiner, Art Unit 1645
October 24, 2025