DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 6-15 are pending in the instant application. Claims 8-11, 14, 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claims 1, 6, 7, 12, 13; species A; and reduced transaminase C activity are under consideration in this Office Action.
In view of the claim amendments filed 02/05/2026, the previous rejections of record have been withdrawn in favor of the instant rejections of the claims stated below.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1, 6, 7, 12, 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amended claims are drawn to a broad and widely varying genus of microorganisms producing L-valine having any one selected from the group consisting of (1) to (6) below:(1) enhanced dihydroxy-acid dehydratase activity; and deleted transaminase C activity; (2) enhanced dihydroxy-acid dehydratase activity; and weakened pyruvate dehydrogenase activity; (3) enhanced dihydroxy-acid dehydratase activity; and weakened citrate synthase activity; (4) enhanced dihydroxy-acid dehydratase activity; deleted transaminase C activity; and weakened pvruvate dehydrogenase activity; (5) enhanced dihydroxy-acid dehydratase activity; deleted transaminase C activity; and weakened citrate synthase activity; and (6) enhanced dihydroxy-acid dehydratase activity; weakened pvruvate dehydrogenase activity; and weakened citrate synthase activity, wherein the modified activities are achieved by any genetic modifications. According to MPEP 2163:
“For each claim drawn to a genus: 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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The specification as originally filed does not disclose a representative number of species microorganisms producing L-valine, genus of dihydroxy-acid dehydratases, genus of transaminase C, genus of pyruvate dehydrogenases, and genus of citrate synthases. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict the specific genetic modifications that result in any microorganism having enhanced dihydroxy-acid dehydratase activity.
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants were in possession at the time the application was filed of the claimed genus of microorganisms producing L-valine having any one selected from the group consisting of (1) to (6) below:(1) enhanced dihydroxy-acid dehydratase activity; and deleted transaminase C activity; (2) enhanced dihydroxy-acid dehydratase activity; and weakened pyruvate dehydrogenase activity; (3) enhanced dihydroxy-acid dehydratase activity; and weakened citrate synthase activity; (4) enhanced dihydroxy-acid dehydratase activity; deleted transaminase C activity; and weakened pvruvate dehydrogenase activity; (5) enhanced dihydroxy-acid dehydratase activity; deleted transaminase C activity; and weakened citrate synthase activity; and (6) enhanced dihydroxy-acid dehydratase activity; weakened pvruvate dehydrogenase activity; and weakened citrate synthase activity, wherein the modified activities are achieved by any genetic modifications.
Claim Rejections - 35 USC § 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 of this title, 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.
Claims 1, 6, 7, 12, 13 are rejected under 35 U.S.C. 103 as being unpatentable over
Magnus et al. ("The Identification of Enzyme Targets for the Optimization of a Valine Producing Corynebacterium glutamicum Strain Using a Kinetic Model", 2009, American Institute of Chemical Engineers, Vol. 25, Issue No. 3, Pg. 754-762; IDS filed 01/31/2024) in view of
Chen et al. (“Metabolic engineering of Corynebacterium glutamicum ATCC13869 for L-valine production”, 2015, Metabolic Engineering, Vol. 29, Pg. 66-75; IDS filed 01/31/2024),
US20120065428 (03/15/2012; reference of record).
The arguments filed 02/05/2026 have been considered but are not persuasive.
According to MPEP 2111, claims must be given their broadest reasonable interpretation in light of the specification. Thus, while claims must be given their broadest reasonable interpretation consistent with the specification, limitations of the specification cannot be read into the claims to thereby narrow the scope of the claims. Applicants stated in the arguments filed 02/05/2026 that the present claims are not rendered obvious by the cited references in view of the unexpectedly superior property of increased L-valine production when dihydroxy-acid dehydratase activity is enhanced and transaminase C activity is deleted simultaneously in a microorganism. However, the claims are not limited to of increased L-valine production when dihydroxy-acid dehydratase activity is enhanced and transaminase C activity is deleted simultaneously in microorganism compared to an unmodified microorganism. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Corynebacterium glutamicum of Magnus et al. to overexpress the of ilvD gene encoding dihydroxy-acid dehydratase; delete the three genes aceE, alaT and ilvA combined with the overexpressing the genes ilvB, ilvN, ilvC, lrp1, brnF and brnE as taught by Chen et al.; and make delete the avtA gene encoding transaminase C taught by US20120065428; where one of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a modified Corynebacterium glutamicum that can be used in a method to produce L-valine. Hence, the claimed invention as a whole is prima facie obvious.
The reference teachings and rejection have been restated below.
Magnus et al. teaches the overexpression of ilvD (dihydroxy-acid dehydratase) in combination with reduced expression of aceE (pyruvate dehydogenase) in Corynebacterium glutamicum for increased production of valine. See entire publication and abstract especially Materials section, Methods section, Results section, and pages 754-762.
The teachings of the reference differ from the claims in that the reference does not teach the Corynebacterium glutamicum having reduced transaminase C activity.
Chen et al. teach a L-valine-producing strain was developed from Corynebacterium glutamicum ATCC13869 through deletion of the three genes aceE, alaT and ilvA combined with the overexpression of six genes, namely ilvB, ilvN, ilvC, lrp1, brnF and brnE (see entire publication and abstract especially Materials and methods section, Results and discussion, and pages 67-75).
US20120065428 teaches Corynebacterium strains with reduced avtA (transaminase C) activity and reduced aceE (pyruvate dehydrogenase) activity for producing 2-keto carboxylic acid, the direct precursor of valine (see entire publication and claims especially paragraphs [0006] – [0016]. US20120065428 teaches the following in the claims:
27. A method of producing a 2-keto carboxylic acid or a salt of the 2-keto carboxylic acid, the process comprising:
(a) growing and fermenting a microorganism in a culture medium, to obtain a culture broth comprising the 2-keto carboxylic acid or salt;
(b) purifying the culture broth obtained in (a), to obtain an effluent, wherein the purifying is achieved by at least one selected from the group consisting of ion exchange, extraction, and distillation;
(c) performing at least one operation selected from the group consisting of further purifying, precipitating, and crystallizing the effluent obtained in (b), to obtain the 2-keto carboxylic acid or salt,
wherein the purity of the 2-keto carboxylic acid or salt is 60% by weight or more, and the 2-keto carboxylic acid has a general formula (I) R1—CO—COOH, wherein R1 is a branched alkyl group comprising 3 to 7 carbon atoms.
36. The process of claim 27, wherein the microorganism in (a) is a Corynebacterium strain.
37. The process of claim 36, wherein the Corynebacterium strain is deficient or reduced in at least one protein selected from the group consisting of transaminase B (E.C. 2.6.1.42, endoded by the ilvE-gene), valine-pyruvat transaminase AvtA (E.C. 2.6.1.66, encoded by the avtA-gene), alanine transaminase AlaT (E.C. 2.6.1.2, encoded by the alaT-gene), an E1 subunit of pyruvate dehydrogenase (E.C. 1.2.4.1, encoded by the aceE gene), pyruvate quinone oxidoreductase (E.C. 1.2.2.2, encoded by the pqo gene), and phosphogluco isomerase (E.C. 5.3.1.9, encoded by the pgi gene).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Corynebacterium glutamicum of Magnus et al. to overexpress the of ilvD gene encoding dihydroxy-acid dehydratase; delete the three genes aceE, alaT and ilvA combined with the overexpressing the genes ilvB, ilvN, ilvC, lrp1, brnF and brnE as taught by Chen et al.; and make delete the avtA gene encoding transaminase C taught by US20120065428. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a modified Corynebacterium glutamicum that can be used in a method to produce L-valine. One of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation of success in view of the reference teachings showing modification of Corynebacterium glutamicum for production of products including L-valine. Hence, the claimed invention as a whole is prima facie obvious.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
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