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 .
Response to Amendment
Applicant’s remarks and amendments filed 8/5/2026, in response to the non-final rejection mailed 5/5/2026, are acknowledged and have been fully considered.
Any previous rejection or objection not mentioned herein have been withdrawn based upon Applicant’s amendments to the claims, in light of the presented arguments.
Applicant’s amendment to the claims is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Claims 15-19 remain withdrawn as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse.
Claims 1-3, 5-12 and 20 are pending and have been examined on the merits.
Claim Rejections - 35 USC § 102 /103
New, necessitated by Applicant’s Amendments
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.
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 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.
Claims 1-3, 7-8, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Repetto et al. (“Structure and regulation of KGD2, the structural gene for yeast dihydrolipoyl transsuccinylase. Mol Cell Biol. 1990 Aug;10(8):4221-32. doi: 10.1128/mcb.10.8.4221-4232.1990. PMID: 2115121, on IDS filed 11/9/2023, hereafter “Repetto”), with supporting evidence from “GenBank: AAA34720.1” (NCBI. AAA34720.1, dihydrolipoyl transsuccinylase [Saccharomyces cerevisiae]. First entry: 27-APR-1993).
Repetto discloses the cloning and analysis of the yeast gene KGD2, coding for yeast KE2, in Saccharomyces cerevisiae (Abstract, pg. 4221, right col. and section “Yeast strains and growth media”). Repetto discloses a nucleotide sequence and a corresponding amino acid sequence for yeast KGD2 (e.g. GenBank: M34531, encoding the protein of GenBank: AAA34720.1, which is included with this communication), which is ~90% identical to the amino acid sequence of SEQ ID NO: 1 (see the included alignment in the APPENDIX below).
Repetto discloses the restoration of KGDC activity in mutants transformed with KGD2 on a high-copy-number plasmid (pg. 4225: “The KGDC activity of mitochondria was measured in a wild-type strain, in kgd2 mutants, and in the same strains transformed with the KGD2 gene on a high-copy-number plasmid”, see Figure 5, see especially Lane 1: mitochondria from the wild-type parental strain W303-1A; lane 2: W303-1A transformed with pG104T1; and lane 4: W303AKGD2 transformed with pG104T1). Repetto discloses vectors (i.e. expression cassettes) for expressing KGD2 (Table 2 on pg. 4228). Repetto discloses that “both clones had at least 10 times more immunologically detectable KE2 in their mitochondria than did the wild-type strain” (pg. 4226, left col).
Thus, Repetto discloses a genetic alteration including the introduction of an expression cassette that causes modified yeast cells to produce an increased amount of KGD2 polypeptides comprising an amino acid sequence that is at least 80% identical to the sequence set forth by SEQ ID NO: 1, compared to parental yeast cells.
Therefore, all of the structural requirements of claims 1-3 are anticipated by the yeast cells in Repetto that express the KGD2 gene on a high-copy number plasmid.
Regarding claim 7, Repetto states that there is 10 times more immunologically detectable KE2 in the engineered than in the parental strain, which is greater than a 20% increase (e.g. a 10X increase would be greater than a 100% increase). Regarding claim 8, the levels of mRNA are not directly assayed in Repetto but because the yeast cells produced therein appear to be substantially identical to those of the instant claim, then inherently the mRNA levels would also be increased at least 2-fold. Repetto does disclose that the final protein expression level is at least 10X more.
Because the yeast cells of Repetto fulfill all of the structural limitations required of the instant claims, i.e. they comprise a genetic modification that causes increased expression of yeast KGD2, then these cells will inherently have the same functional properties as those of the instant claims. The functional properties of an organism are the result of its genetics and conditions in which it is raised. When raised under the correct conditions for ethanol fermentation, a common well-known use of S. cerevisiae, these cells would predictably and inherently have the same functional properties.
Thus, the feature of “the modified yeast cells produce during fermentation (which is considered a conditional clause, as this only is when fermentation occurs) an increased amount of ethanol compared to the amount of ethanol produced by otherwise identical parental yeast cells” is deemed to be inherently anticipated by the modified yeast cells disclosed in Repetto.
MPEP § 2112.01.I. describes that when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent, and that where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding claim 20, Repetto teaches culturing, i.e. fermenting, the cells on carbohydrate sources, including glucose, glycerol, and galactose (see “Yeast strains and growth media”, pages 4221-4222). The instant claims do not require anaerobic fermentation and the instant disclosure discusses both aerobic and anaerobic fermentation as viable options (see e.g. [033]-[034] of the instant specification). Because the yeast cells of Repetto over-expressing KGD2 are essentially identical as the cells encompassed by claim 1, the growth of these cells on a suitable carbohydrate source, in the manner of the instant invention will inherently result in the same outcome (ee MPEP § 2112.02). Thus, the disclosure of Repetto, including culturing the modified cells therein on carbohydrates, is deemed to anticipate the method of claim 20.
In the alternative, even if the claimed composition (with respect to undisclosed genetic background or minor modifications) is not identical to the referenced composition and effects, with regard to unidentified characteristics, the differences between that which is claimed and that which is disclosed, is so slight that the referenced composition is likely to inherently possess the same characteristics of the claimed composition, particularly in view of the similar characteristics which they have been shown to share and by the functions of the component materials (e.g. a yeast cell having an expression cassette for increased expression of yeast KGD2) inherently present in each, and which functions are inclusive of those appreciated in the instant disclosure as being present (see e.g. MPEP 2112.02 at Ex parte Novitski, in reference to reference-silent functioning of biological materials providing anticipation of the functions based upon the material itself, noting the reference of “Dart” therein did not appreciate the claimed function but still anticipated the function based on the inherent function of the material, and that the Applicant’s disclosure appreciating the function upon usage thereof as further evidence of the presence of the function).
Therefore, the claimed composition comprising a yeast cell modified to have increased expression of the α-ketoglutarate dehydrogenase subunit KGD2, and the increased ethanol production effects upon fermenting said yeast, would have been anticipated, or in the alternative, at least obvious to those of ordinary skill in the art within the meaning of 35 USC § 103(a) by the teachings of Repetto, before the effective filing date of the instant invention.
From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, because Repetto teaches expressing KGD2 enzymes (including those having at least 80% sequence identity to SEQ ID NO: 1) in S. cerevisiae and ethanolic fermentation of baker’s yeast are well-known to one of ordinary skill in the art.
Accordingly, claims 1-3, 7, 8, and 20, as a whole, would have been at least prima facie obvious, if not anticipated by Repetto, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
Please note, since the Office does not have the facilities for examining and comparing Applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and “as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
Allowable Subject Matter
Claims 5-6 and 9-12 are objected to as being dependent upon a rejected base claim, but appear to be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter. The relevant prior art does not expressly teach nor reasonably suggest modified yeast cells as in claims 5 and 6, wherein the nucleic acid comprises a promoter with the particular properties of claim 5, nor specifically selecting the ADR1 promoter set forth by SEQ ID NO: 3. These result in unexpected benefits that would not have been predictable from the teachings of Repetto and other relevant art.
The additional genetic modifications set forth in claims 9-12 are not expressly taught in Repetto and there would have been no motivation or suggestion to one of ordinary skill in the art to further modify yeast cells to include these with a reasonable expectation of success.
As allowable subject matter has been indicated, applicant's reply must either comply with all formal requirements or specifically traverse each requirement not complied with. See 37 CFR 1.111(b) and MPEP § 707.07(a).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm 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, Anand Desai can be reached at 571-272-0947. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
APPENDIX: Alignment of yeast KGD2 from Repetto with SEQ ID NO: 1.
Qy: SEQ ID NO: 1
Db: AAA34720.1.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 2082 90.2 475 1 AAA34720.1 dihydrolipoyl tran
ALIGNMENTS
RESULT 1
AAA34720.1
Query Match 90.2%; Score 2082; DB 1; Length 475;
Best Local Similarity 91.3%;
Matches 419; Conservative 14; Mismatches 26; Indels 0; Gaps 0;
Qy 1 MLSRATRTAAAKSLVKSKVARNVMAASFVKRHASTSLFKQANKVESLGSIYLSGKKISVA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLSRATRTAAAKSLVKSKVARNVMAASFVKRHASTSLFKQANKVESLGSIYLSGKKISVA 60
Qy 61 ANPFSITSNRFKSTSIEVPPMAESLTEGSLKEYTKNVGDFIKEDELLATIETDKIDIEVN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ANPFSITSNRFKSTSIEVPPMAESLTEGSLKEYTKNVGDFIKEDELLATIETDKIDIEVN 120
Qy 121 SPVSGTVTKLNFKPEDTVTVGEELAQVEPGEAPAEGSGESKPEPTEQAEPSQGVAARENS 180
||||||||||||||||||||||||||||||||||||||||||||||||| : :
Db 121 SPVSGTVTKLNFKPEDTVTVGEELAQVEPGEAPAEGSGESKPEPTEQAEHRKVSPQGKTQ 180
Qy 181 SEETASKKEAAPKKEAAPKKEVTEPKKADQPKKTVSKAQEPPVASNSFTPFPRTETRVKM 240
: :|: :|: :|:: |: ||||||||||||||||||||||||||||||||
Db 181 VRKRLQRKKLLQRKKPLQRKKLQNQKRTDQPKKTVSKAQEPPVASNSFTPFPRTETRVKM 240
Qy 241 NRMRLRIAERLKESQNTAASLTTFNEVDMSALMEMRKLYKDEIIKKTGTKFGFMGLFSKA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 NRMRLRIAERLKESQNTAASLTTFNEVDMSALMEMRKLYKDEIIKKTGTKFGFMGLFSKA 300
Qy 301 CTLAAKDIPAVNGAIEGDQIVYRDYTDISVAVATPKGLVTPVVRNAESLSVLDIENEIVR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTLAAKDIPAVNGAIEGDQIVYRDYTDISVAVATPKGLVTPVVRNAESLSVLDIENEIVR 360
Qy 361 LSHKARDGKLTLEDMTGGTFTISNGGVFGSLYGTPIINSPQTAVLGLHGVKERPVTVNGQ 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LSHKARDGKLTLEDMTGGTFTISNGGVFGSLYGTPIINSPQTAVLGLHGVKERPVTVNGQ 420
Qy 421 IVSRPMMYLALTYDHRLLDGREAVTFLKTVKELIEDPRK 459
|||||||||||||||||||| : ::||||||||||||||
Db 421 IVSRPMMYLALTYDHRLLDGEKLLSFLKTVKELIEDPRK 459
Prosecution Insights