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 .
Status of Claims
Receipt of Arguments/Remarks filed on 1/12/2026 is acknowledged. Claims 13, 16-17 and 20-36 are pending. Claims 13, 29, 31, and 33 were amended. New claims 35 and 36 were added.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 12/12/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections
The rejection of claims 13, 16-17, 22-24, and 31-32 under 35 U.S.C. § 102 is withdrawn.
The rejection of claims 21, 25-30, and 33-34 under 35 U.S.C. § 103 is withdrawn.
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 13, 16-17, 20, 22-24, 28-29, and 31-36 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.
Regarding written description, 35 U.S.C. 112(a) and the first paragraph of pre-AlA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention (MPEP § 2163(I)).
MPEP 2163(II)(A)(3)(a)(i and ii) states that 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., .759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). 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 structure of independent claims 13 and 31 is a microorganism strain from the Enterobacteriaceae family wherein the microorganism comprises a mutated, modified, or deleted ppsA gene and expresses cysE with reduced feedback inhibition. Claims 13 and 31 additionally recite the functional limitation that the strain has increased L-cysteine production relative to a microorganism strain having wild-type enzyme activity. There is not sufficient written description support in the specification for a microorganism strain having only an inactivation of ppsA and expressing cysE with reduced feedback inhibition, with the function of increased L-cysteine production.
The examples in the specification are directed to a wildtype strain E. coli W3110 or a wildtype P. ananatis strain, as well modified versions of these strains comprising plasmid pCYS, or plasmid pCYS and a ppsA modification (see instant specification Tables 1-4). E. coli W3110 (wildtype) does not produce cysteine (instant specification Table 2). Plasmid pCYS comprises the cysEX allele, which encodes a serine O-acetyltransferase having a reduced feedback inhibition by cysteine, an efflux gene ydeD, as well as the N-terminal 317 amino acids of the SerA protein, or a feedback-resistant variant of 3-phosphoglycerate dehydrogenase (see instant specification pp. 32-33 Ex. 4). All of the strains disclosed by applicant which have increased cysteine production compared to wildtype comprise the pCYS plasmid, i.e. a strain comprising at least cysEX, ydeD, and SerA.
The specification does not disclose a strain which comprises only ppsA modification and cysE expression and has increased cysteine production. However, claims 13 and 31 read on a strain which has only these modifications and increased cysteine production compared to WT. Therefore, it is not clear that applicant was in possession of the full scope of the invention.
Similarly, independent claims 28 and 33 recite a microorganism strain wherein ppsA is inactivated or modified, with increased L-cysteine production. For the same reasons as discussed above, there is not written description support for a strain having only a modification to ppsA and increased L-cysteine activity, as the only strains disclosed have the additional expression of cysEX, ydeD, and SerA. Further, there are no examples of a Corynebacterium glutamicum strain with ppsA inactivated. As claims 28 and 33 read on a strain which has only a ppsA mutation and increased cysteine production, and such a strain is not disclosed in the specification, it is not clear that applicant was in possession of the full scope of the invention.
There is written description support for an E. coli or Pantoea ananatis strain comprising a ppsA modification and expressing a serine O-acetyltransferase with reduced feedback inhibition, an efflux gene, and a feedback-resistant variant of 3-phosphoglycerate dehydrogenase (i.e., the pCYS plasmid) with increased cysteine production.
Further, claim 29 recites the limitation “a gene homologous to these genes” with “a DNA sequence which is at least 80% identical to these genes”. There is not sufficient written description support for a homologous gene with a sequence that is 80% identical to the claimed genes and maintains the claimed function of phosphoenolpyruvate synthase enzyme activity and increased cysteine production. There is not a sufficient structure-function relationship to make clear to a skilled artisan which regions of SEQ ID NOs: 1 or 3 can differ compared to the wildtype and still retain the claimed enzyme activity. SEQ ID NO: 1 has 3000 nucleotides and SEQ ID NO: 3 has 3062 nucleotides. This means that ~600 nucleotides may vary between the wild type and a homologous gene having 80% identity. This encompasses a vast number of potential sequences, and it is not clear which of these many sequences would maintain enzyme function. For these reasons, claim 29 fails to comply with the written description requirement.
Claims 16-17, 20, 22-24, 30, 32, and 34-36 are included in this rejection because they depend on a rejected claim and do not clarify the issue.
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 13, 16-17, 20-27, 30-32, and 34-36 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 13 and 31 recite “serine O-acetyltransferase (cysE)”. The use of parentheses around cysE makes the scope of this limitation unclear. Specifically, it is not clear whether the serine O-acetyltransferase must be cysE, or if cysE is merely exemplary of a serine O-acetyltransferase and not required.
Similarly, claims 32 and 34 recite “or acetate salts derived therefrom”, “and salts thereof”. The parentheses around these limitations render the claims indefinite, as it is not clear whether these limitations are required or optional.
It is suggested that the claims be amended to remove these parentheses.
Claim 30 recites the limitation "the efflux gene". There is insufficient antecedent basis for this limitation in the claim. Claim 30 depends on claim 29, which depends on claim 28. Claims 28 and 29 do not recite an efflux gene. Therefore, it is unclear what “the efflux gene” in claim 30 refers to.
Claims 16-17, 20-27, and 35-36 are included in this rejection because they depend on a rejected claim and do not clarify the issue.
Allowable Subject Matter
Regarding independent claims 13, 28, 31, and 33, the closest prior art is Zhou et al., Curr Microbiol; 62(3):981-9, Ziyatdinov US 2005/0124049 A1, Kaberdina et al., Genetics and Genomics; 294(5):1359-71, and Mockel et al., US 2002/0045224 A1.
Zhou teaches a strain with inactivated ppsA enzyme activity by complete deletion of the ppsA gene (Zhou pg. 982 para. 2; pg. 982 “Strains”).
Zhou does not teach that the strain additionally expresses a serine O-acetyltransferase (cysE) which, in comparison with the corresponding wild-type enzyme, has a feedback inhibition by cysteine that is reduced by a factor of at least two (claims 13, 31). Zhou does not teach that the strain has increased cysteine production relative to wildtype. Zhou does not teach that a strain with a ppsA deletion and increased cysteine production is used in a fermentative process for producing cysteine (claims 28 and 33).
Ziyatdinov teaches a strain overexpressing mutant cysE (serine O-acetyltransferase) that is free from feedback inhibition from cysteine, an efflux gene ydeD, and a mutant serA gene (phosphoglycerate dehydrogenase) that is free from feedback inhibition by serine (Ziyatdinov pg. 4 para. 67-70; pg. 5 Example 1). Ziyatdinov teaches that this strain is used for fermentative production of L-cysteine (Ziyatdinov pg. 4-5 para. 70).
Kaberdina teaches E. coli central carbon metabolism and the genetic regulation of E. coli metabolic pathways (Kaberdina “Introduction”). Kaberdina teaches ppsA, which converts pyruvate to phosphoenolpyruvate (PEP), is important for E. coli central carbon metabolism (Kaberdina pg. 1365 para. 1). Kaberdina teaches that E. coli central carbon metabolism comprises biochemical pathways that are important for energy generation and production of intermediate metabolites that serve as precursors for biosynthesis of amino acids (Kaberdina pg. 1360 first full para.).
However, it would not have been obvious for a skilled artisan to combine these teachings and arrive at a strain with both a ppsA deletion/inactivation and expression of feedback resistant cysE that is free from feedback inhibition by serine. It would also not have been obvious to utilize a strain with a ppsA deletion in a process of fermentative production of cysteine. A skilled artisan would not expect that a deletion or inactivation of ppsA would result in increased cysteine production. Based on prior art teachings, increased cysteine production would not be expected for a strain with a ppsA deletion. For example, Mockel et al., US 2002/0045224 A1, teaches strains for production of amino acids including L-cysteine which have enhanced expression of ppsA (Mockel p. 1 para. 1, 7, 33). As taught by Zhou and Kaberdina, ppsA deletion would be expected to render a cell unable to catalyze a reaction from PEP towards glyceraldehyde-3-phosphate and 3-phosphoglycerate, which is the point where serine and cysteine biosynthesis breaks off from central carbon metabolism. Therefore, a skilled artisan would have had no motivation to combine the teachings of Zhou, Ziyatdinov, and Kaberdina. A strain with ppsA deletion/inactivation and expression of feedback resistant cysE, or use of such a strain in a fermentative process for producing cysteine, is not obvious in view of the prior art.
As set forth above in the rejection under 35 U.S.C. § 112(a), a microorganism having only a ppsA inactivation or a ppsA inactivation and modified cysE expression lacks written description support. If the independent claims 13, 28, 31, and 33 are amended to recite a microorganism strain having a ppsA inactivation, expression of cysE with reduced feedback inhibition, an efflux gene, and a serine feedback-resistant variant of 3-phosphoglycerate dehydrogenase; and if the claims are amended to overcome the rejection of claim 29 under 35 U.S.C. § 112(a) and of claims 13, 16-17, 20-27, 30-32, and 34-36 under 35 U.S.C. § 112(b); the claims would be allowable.
Response to Arguments
Applicant’s arguments, filed 1/12/2026, with respect to a strain having both a ppsA inactivation and expression of feedback resistant cysE have been fully considered and are persuasive. In view of these arguments and amendments to independent claims 13 and 31, The rejections of claims under 35 U.S.C. § 102 and 103 have been withdrawn.
However, as discussed above, the claims are rejected under 35 U.S.C. § 112(a). Applicant argues that only strains with deregulated cysteine metabolism, as realized by a modified cysE (contained in plasmid pCYS) actually produces cysteine (see applicant arguments/remarks from 1/12/2026, p. 9). The pCYS plasmid additionally includes ydeD and SerA. As demonstrated in Table 2 of applicant arguments, a strain with only a modification to reduce ppsA activity does not produce cysteine, and therefore does not exhibit increased cysteine production compared to wildtype. Thus, it appears that all of these modifications are required for increased cysteine production, not just ppsA inactivation and/or cysE expression. For this reason, a strain with ppsA inactivation and/or feedback resistant cysE expression with increased cysteine production lacks written description support.
Conclusion
Claims 13, 16-17, and 20-36 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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