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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submissions filed on 27 July 2026 and 22 May 2026 has been entered.
Claim Status
The amended claim set filed 22 May 2026 is acknowledged. Claims 1, 5-7, 9-13 and 15-16 are currently pending. Of those, claims 1, 6, 9, and 15 are currently amended, and no claims are new. Claims 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 21 July 2025. Claims 2-4, 8, 14, and 17-19 are cancelled. Claims 1, 5-7, 9-10 and 15-16 will be examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 27 July 2026 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. A signed copy of the statement is attached with this action.
Response to Arguments
The Applicants’ arguments filed 22 May 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Final Office Action mailed 25 Feb 2026 will be referred to as “NFOA.”
Objection(s) and Rejection(s) Withdrawn
The objections to claims 1 and 6 are withdrawn in view of the claim amendments.
The 35 U.S.C. 112(b) rejections related to claims 1 (NFOA par. 12) and 15 (NFOA par. 14) are withdrawn in view of the claim amendments and arguments.
Rejection(s) Maintained
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
Claims 15 remains objected to because of the following informalities: typographical error, claim 15 still reads “ribose-5-phoshate” but should read “ribose-5-phosphate”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 9 remains 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.
Regarding claim 9, the claim has been amended to recite “The SM of claim 1, having the … formate and acetate production profile of ATCC deposit accession number PTA- 126783, when grown on methanol.” The specification does not define the term “production profile”, and this term does not have a generally accepted definition in the field at the time of filing. Accordingly, one of ordinary skill in the art would not be able to determine whether only the chemical identities must match or also the amounts produced (i.e. does producing any level of formate and acetate match the profile, or are specific amounts required?), and how much variation (if any) is permitted within the same “production profile”. The arguments point to Figure 7 and related text (Remarks pg. 5), but Figure 7G does not indicate how to determine whether another strain has the same fermentation profile as the graph, must the strain’s fermentation match the graph exactly? The related text at [0019] and [0177] do not clarify this issue. Therefore, one of ordinary skill would not be able to clearly determine whether a potential SM has the same “production profile” as the deposited strain, and the claim boundaries are unclear.
Response to Arguments
Applicant argues (Remarks pg. 5) that the claim has been amended and support can be found in Figure 7 and related text.
This argument has been carefully considered but is not found persuasive. The previous rejection explained why Figure 7 and related text are not considered to have the required support, and the arguments do not point out any flaws in the prior rationale. The following claim text is suggested to overcome this rejection. This text could not be suggested by examiner’s amendment because there has not been a Power of Attorney filed and accepted in this case.
Claim 9: The SM of claim 1, having the doubling time
New Rejection(s)
Claim Rejections - 35 USC § 112(b)
Claim 5 is 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.
Regarding claim 5, the claim reads “wherein the SM has one or more copy number variations of 2 to 85 of a region between yggE to yghO, rrsA to rrlB, and/or ygiG to smf, or osmC to dosP, or any region combinations thereof.” The confusing grammar “has one or more copy number variations of 2 to 85 of a region” and the multiple groupings (note the “and/or”, “or” and second “or”) would prevent one of ordinary skill in the art from clearly determining claim scope. The multiple conjunctions in this phrase prevents one of ordinary skill from understanding what options are claimed – is the “and/or” before the third to the last option meaningful to limit the combinations of region options listed, given the removal of the “and” from before the second to last region? Also, does “of 2 to 85 of a region” refer to the number of copy number variation regions, or the number of repeats within a single region, or the total number of repeats? Therefore, the claim is indefinite.
In the interest of compact prosecution, the claim is interpreted as follows. This text could not be suggested by examiner’s amendment because there has not been a Power of Attorney filed and accepted in this case.
Claim 5: The SM of claim 1, wherein the SM comprises between 2 and 85 copies of at least one region selected from the following regions: yggE to yghO, rrsA to rrlB, ygiG to smf, or osmC to dosP.
Allowable Subject Matter
Claims 1, 6-7, 10-13, and 16 are allowed. Per MPEP 281.04, rejoinder should be considered “when all the claims directed to the elected invention are in condition for allowance” (emphasis added). The following is a statement of reasons for the indication of allowable subject matter:
For claim 10: The specific deposited strain is novel and the collection of mutations in this strain would not have been obvious in view of the art. Also, this claim would have been rejected as not enabled under 35 U.S.C. 112(a) but for the information about the deposit and the statement in the specification that “This deposit will be maintained at an authorized depository and replaced in the event of mutation, nonviability or destruction for a period of at least five years after the most recent request for release of a sample was received by the depository, for a period of at least thirty years after the date of the deposit, or during the enforceable life of the related patent, whichever period is longest. All restrictions on the availability to the public of these cell lines will be irrevocably removed upon the issuance of a patent from the application.” [0122].
For other claims: The collection of mutations present in the modified bacteria are both novel and non-obvious. The closest art is Papoutsaki et al. (US-20200017888-A1, published 16 Jan 2020, filed 13 Feb 2018; hereafter Papoutsaki; PTO-892 mailed 3 Sep 2025). Papoutsaki teaches a recombinant E. coli expressing Bacillus stearothermophilus 2334 (Bst) methanol dehydrogenase (MDH), Bacillus methanolicus MGA3 (Bme) hexulose phosphate synthase (HPS) and Bacillus methanolicus MGA3 (Bme) hexulose phosphate isomerase (PHI) [0017]. Papoutsaki compares E. coli strains with and without deletions in glucose-6-phosphate isomerase (pgi) genes [Figure 7, 0022] (i.e. comprises pgi, as in claims 15-16). Papoutsaki also teaches that the strains can comprise RpiA [0093], Tkt, or Tal [0048]. Papoutsaki teaches deletions in GapA and FrmA [0094]. Papoutsaki does not teach a mutated polypeptide having glucose phosphate isomerase (PGI) activity and having higher activity than wild-type (instant claim 1 and dependent claims), or a reduction or elimination/knockout of a polypeptide having phosphocarrier protein (HPr or PtsH) activity; a polypeptide having proline uptake regulator Q (ProQ) activity; a polypeptide having 6-phosphofructokinase 1 (PfkA) activity (instant claims 1 and 15 and dependent claims).
The art teaches that modifying the bacteria of Papoutsaki to have the additional mutations is not obvious. The instant specification identified this combination of mutations by a process of experimental evolution (Figure 1B). However, Chen et al. (2018; PTO-892 mailed 3 Sep 2025) teaches “The outcome of evolution is sometimes counter-intuitive and cannot be predicted rationally a priori” (pg. 264 col. 2 par. 2). So, even if it were argued that it would be obvious to perform the same process of experimental evolution, applying the method would not result in the claimed product with a reasonable expectation of success. Confirming this, Chen used experimental evolution to produce a synthetic methylotroph (Abstract) and found that the evolved strain had a deletion in the frmA gene (Abstract, Table 3), but does not teach elimination or knockout of the other eliminated or knocked out genes in claims 1 and 15.
Also, choosing the claimed combination of mutations is not obvious. Bennett et al. (2018; PTO-892) “demonstrate improved co-utilization of methanol and glucose by deleting the phosphoglucose isomerase gene (pgi), which rerouted glucose carbon flux through the oxidative PPP” (Abstract), showing it would not be obvious based on the art at the time of filing to increase the pgi activity as in claim 1. Also, Papoutsaki’s teaching to delete GapA and FrmA [0094] is in a list of many different genes that could be deleted, but the other genes deleted in the claims are not listed despite the many options contemplated in the reference. A search of the art has not found a specific motivation to delete these other eliminated or knocked out genes in the context of methanol-producing bacteria. While the deleted genes from claims 1 and 15 are known and could be knocked out with a reasonable expectation of success, choosing the specific claimed combination of genes from the list of all possible mutations that could be made requires choosing from a list of options that is so large it should not be considered finite.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA N DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-F 8:30-4:30 (EDT/EST).
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AMELIA N DICKENS
Examiner
Art Unit 1645
/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
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