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 .
DETAILED ACTION
Claims 1-4, 6-10, and 12-21 are pending.
Election/Restrictions
Applicant’s election of Group I, claims 1-4, 6-8, and 17 in the reply filed on 4/7/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 9-10, 12-16, and 18-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 4/7/2026.
Claims 1-4, 6-8, and 17 are examined herein.
Claim Rejections - 35 USC § 112
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 4 and 6-8 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 4 recites the broad recitation “an amino acid other than V at the position corresponding to position 198 in SEQ ID NO: 2,”, and the claim also recites “preferably wherein said amino acid is F, I, Y, or W,” which is the narrower statement of the limitation, and “, more preferably wherein said amino acid is F,” which is an even narrower statement of the limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 4 is further indefinite for “wherein the SinR variant provides for a decreased duration of the lag phase and/or an increased growth-rate of the bacterium as compared to SEQ ID NO: 2.” Claim 4 is indefinite because SEQ ID NO: 2 is an amino acid sequence rather than a bacterium, thus the basis for comparison of duration of the lag phase and/or growth rate is unclear.
Claim 8 is indefinite for requiring an average nucleotide identity percentage compared to an unknown reference sequence in (c) and (d).
Claims 6-7 are indefinite for depending from a rejected base claim and not rectifying the source of indefiniteness discussed above.
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 1, 4, and 6-7 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.
Claim 4 recites a genus of SinR variants with at least 90% sequence identity with SEQ ID NO: 2 comprising an amino acid other than V at the position corresponding to position 198 in SEQ ID NO: 2, wherein the SinR variant provides for a decreased duration of the lag phase and/or an increased growth-rate of the bacterium as compared to SEQ ID NO: 2. Claim 4 is interpreted as comparing the duration of lag-phase and growth rate of the Moorella species comprising the SinR variant to the duration of lag-phase and growth rate of the same Moorella species comprising SEQ ID NO: 2 cultured under identical conditions. Dependent claim 6 limits the amino acid to F, I, Y, or W and claim 7 limits the amino acid to F. SEQ ID NO; 2 is 300 amino acids long, so a variant with at least 90% identity to SEQ ID NO: 2 differs from SEQ ID NO; 2 by as many as 30 amino acids.
The specification discloses evolving M. thermoacetica under selection pressure over 2500 generations (page 24, lines 1-8) The evolved strain has a phenylamine at position 198 of SEQ ID NO: 2 (page 24, line 32). The specification discloses that analysis of the protein structure of SinR of M. thermoacetica shows that it resembles SinR of Bacillus although the two proteins are not identical (lines 3-4 on page 25). The specification hypothesizes that V198 in M. thermoacetica may be equivalent to either T60 or L61 in B. subtilis (lines 6-7 on page 25). The specification discloses that the V198F mutation in SinR decreases the duration of the lag phase upon inoculation into fresh medium after a longer incubation period (line 10 on page 11). The specification hypothesizes that SinR affects the stability of the protein, its affinity for the anti-repressor SinI and/or its ability to oligomerize (lines 13-15 on page 11).
Lewis et al. (Journal of molecular biology 283.5 (1998): 907-912) teaches that SinR is a tetrameric repressor protein that binds to the promoters of genes essential for entry into sporulation and prevents their transcription (Abstract). This repression is overcome through the activity of SinI, which disrupts the SinR tetramer through the formation of a SinI-SinR heterodimer (Abstract). Figure 2 illustrates critical residues in the multimerisation domain of SinI-SinR heterodimer (Figure 2 caption). Lewis does not teach any variants of SinR.
Bai et al. (Genes & development 7.1 (1993): 139-148) generates SinR deletion mutants of Bacillus subtilis and studies the phenotypic effects (Table 1). Bai teaches that the binding of SinI to the multimerization domain of the SinR functional dimer causes an undefined change in the structure, which prevents DNA binding (Figure 10). Although Bai generates a deletion mutant of SinR, Bai does not teach any other variants of SinR.
Thus, the state of the art illustrates a complex and unpredictable relationship between the structure of the SinR protein and its biological functions. Since the functions of SinR require specific three-dimensional conformations (tetramer and heterodimer formation), then a structure-function correlation between the amino acid sequence and its functions would require the ability to predict the effect of single amino acid mutations and combinations of amino acid mutations on the three-dimensional structure of the protein.
Based on the small number of species of SinR variants disclosed by Applicant, the lack of SinR variants taught by the prior art, and the lack of a structure-function correlation between the amino acid sequence of SinR and the function of a decreased duration of the lag phase and/or an increased growth-rate of the bacterium as compared to a bacterium comprising SEQ ID NO: 2, the person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genus of SinR variants.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 8, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Kimura et al. (Journal of bioscience and bioengineering 121.3 (2016): 268-273) in view of Sandoval et al. (Biotechnology for biofuels 8.1 (2015): 227) and Brown et al. (Molecular microbiology 14.3 (1994): 411-426) as evidenced by Dürre et al. (Anaerobe 10.2 (2004): 69-74).
Kimura teaches culturing Moorella thermoacetica in the presence of glycerol during syngas fermentation improves the yield of ethanol (Abstract).
Regarding claims 1-3 and 8, Kimura does not teach deleting spo0A.
Sandoval teaches that a Clostridium pasteurianum spo0A deletion mutant increases the growth rate of the strain and improves the tolerance to glycerol (Abstract Results).
Brown characterizes spo0A homologues in diverse Bacillus and Clostridium species (Title), including both Clostridium pasteurianum and Clostridium thermoaceticum (Fig. 2). Clostridium thermoaceticum is a synonym for Moorella thermoacetica as evidenced by Dürre (page 72, right column, first full paragraph).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to delete spo0A in M. thermoacetica in order to increase the growth rate and glycerol tolerance of the strain. The person of ordinary skill in the art would have had a reasonable expectation of success given that Brown teaches that M. thermoacetica (C. thermoaceticum) encodes spo0A and Sandoval teaches that deleting spo0A in Clostridium pasteurianum increases growth rate and glycerol tolerance.
Regarding claim 17, Kimura teaches M. thermoacetica Y72 (page 269, left column, Materials and Methods, Strains and media, lines 1-2) rather than ATCC 39073.
However, Brown teaches M. thermoacetica ATCC 39073 (Table 3).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace M. thermoacetica Y72 with M. thermoacetica ATCC 39073 because strain Y72 was recently isolated from a soil sample (Kimura page 268, right column, first full paragraph), whereas ATCC 39073 is a deposited strain at the American Type Culture Collection (ATCC). Thus, the person of ordinary skill in the art would have been motivated to make the method easier to practice by using a more accessible strain. The person of ordinary skill in the art would have had a reasonable expectation of success because the strains are both M. thermoacetica.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at (571)272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
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