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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 3, 5, 7, 8, 14-16, 22, and 48 (and Applicant’s elected species of chorismite pyruvate lyase, M. extorquens methanol dehydrogenase promoter, SEQ ID NO: 6, and SEQ ID NO: 4 in the reply filed on 01/28/2026 is acknowledged.
Claim 23, 25, 29, 35-36, 38, 44-47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 01/28/2026.
The species of DAHP synthase, shikimate kinase, DHQ, promoters and corresponding nucleic acids sequences, polypeptides, and exogenous amino acid sequence are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/28/2026.
Priority
The instant application claims benefit to PCT/US2021/052676, filed on 09/29/2021 and US Provisional Application No. 63085567, filed 09/30/2020 and is acknowledged. The instant claims herein are examined using the effective filing date of 09/30/2020 for the basis of any prior art rejections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 03/28/2023 was properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) was considered.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 is objected to because there is a comma after “EC 4.1.2.15”. The examiner suggests removing the comma. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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, 3, 5, 7-8, 14-16, 22, and 48 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.
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 inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
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). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
Claim interpretation: The claims require, inter alia, “A method of producing para-hydroxybenzoic acid (pHBA) or a derivative thereof, the method comprising: culturing a recombinant microorganism in a fermentation broth; adding a carbon source to the fermentation broth; and isolating the pHBA from the fermentation broth; wherein the recombinant microorganism comprises a genetically engineered pathway comprising an exogenous 3 -deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase of EC 4.1.2.15, or EC 2.5.1.54 wherein the exogenous DAHP synthase of EC 4.1.2.15, or EC 2.5.1.54 comprises a feedback-inhibition resistant mutation in the wild-type amino acid sequence of the DAHP synthase.” A “feedback-inhibition resistant mutation in the wild-type amino acid sequence of the DAHP synthase” as claimed has been interpreted to be any mutation, including any deletions, substitutions, additions, etc. anywhere within/along the wildtype sequence of DAHP synthase with the functional property of creating resistance to feedback inhibition in the recombinant microorganism. The question at issue is whether the skilled artisan would understand the correlation between structure of the broad genus of DAHP synthase mutants and ability to create resistance to feedback inhibition in the recombinant microorganism, as there is no correlation or defining characteristic that would convey the identity of the structure necessary to perform the claimed function.
Reduction to practice and disclosure of drawings or structural chemical formulas: Applicant discloses in the specification AroGEcoS180F (E. coli feedback-inhibition resistant DAHP synthase) in SEQ ID NO: 1, SEQ ID NO: 53, 61, 65 (tagged DAHP synthase) (see Table 1). Applicant has not disclosed any other mutations in the wildtype DAHP synthase that provides feedback-inhibition resistance.
Sufficient, 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: Applicant has not provided information as to the defining structural characteristics that would lead one of ordinary skill in the art to the identity of a DAHP synthase mutant capable of “exhibiting feedback resistance”. Applicants are claiming, essentially, any mutation along the sequence of DAHP synthase (additions, substitutions, deletions, etc.) that would impart this function onto the enzyme. This means that the DAHP synthase mutant has a functional limitation of having feedback-inhibition resistance. However, under broadest reasonable interpretation, the enzyme can encompass any mutated sequence or portion thereof, but Applicants have not disclosed which portion of the enzyme is necessary for the functional limitation as claimed. Even with knowledge in the art regarding the mutation of amino acids, one of ordinary skill would not know what structural features are required for the outcome of conferring feedback inhibition resistance in the protein without a recognized correlation between structure and function. In essence, Applicants are describing a critical portion of their invention by function. This is not sufficient to meet the written description requirement.
Lack of support for massive genus of DAHP synthase mutants: In support of the claimed genus, the specification demonstrates only the serine to phenylalanine mutation at position 180 is capable of providing feedback-inhibition resistance (see, e.g., Table 1). However, there is no support in the specification feedback-inhibition resistance using any and all possible mutations in the wildtype DAHP synthase sequence (e.g., any mutation at position 180, or any mutation anywhere along the sequence). Applicant has not provided any information that would allow one of ordinary skill to reasonably understand that any mutation is capable of providing the functional limitation claimed.
Thus, the data generated for the use of the S180F mutation to confer feedback-inhibition resistance cannot reasonably be extrapolated to and applied to support possession of the entire claimed genus of DAHP synthase mutants as claimed, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the claimed genus of subject(s) in need thereof, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the claimed genus. Therefore, the claims are rejected under 35 U.S.C. 112(a) for lack of written description.
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.
Claims 1, 3, 5, 7-8, 14-16, 22 and 48 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.
Claim 1 recites the limitation "the wild-type amino acid sequence of the DAHP synthase" in line 14. There is insufficient antecedent basis for this limitation in the claim as there is no previous recitation of any "wild-type amino acid sequence” earlier in the claim. Thus, the claim is indefinite. Please note that all the dependent claims are also indefinite due to dependency on indefinite claim 1.
Claim 7 recites “wherein the genetically engineered pathway: is encoded by a single vector driven by a single promoter, wherein the promoter is: a constitutive promoter; an inducible promoter; selected from a M. extorquens methanol dehydrogenase promoter, an E. coli ribulokinase promoter, an E. coli beta-galactosidase promoter, or a bacteriophage lambda promoter; or encoded by a nucleic acid sequence set forth in SEQ ID NO:6; or comprises a nucleic acid sequence selected from SEQ ID NOs: 6, 45, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, or a combination of any two or more thereof.” The language of the claim is prima facie confusing because it is unclear whether the limitation after the phrase “inducible promoter” is a Markush group of inducible promoters or a group of other kinds of promoters because of the semi-colon. Thus, the claim is indefinite. For the purposes of compact patent prosecution, the examiner is interpreting the phrase “inducible promoters” to encompass the Markush group of promoters following the phrase. Please note that claim 8 is also indefinite due to dependency on indefinite claim 7.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 5, as amended, is dependent on claim 48. A claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102/103
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 (i.e., changing from AIA to pre-AIA ) 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 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.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim 1 and 48 are rejected under 35 U.S.C. 102(a)(1)(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Ward et al (US 6210937 B1; cited in Applicant 03/28/2023 IDS).
Ward teaches a method for producing p-hydroxybenzoic acid biocatalytically in a microbial cell transformant via the common pathway of aromatic compounds synthesis (a method of producing pHBA as in claim 1), said method comprising: culturing the cell transformant in media containing an assimilable carbon source under conditions conducive to the assimilation of said carbon source, said cell transformant comprising exogenous DNA sequences encoding DAHP synthase (culturing a recombinant microorganism in a broth, adding a carbon source, and comprises a genetically engineered pathway comprising a nucleic acid sequence encoding a DAHP synthase as in claim 1), transketolase, PEP synthase, chorismate synthase, shikimate kinase, EPSP synthase, DHQ synthase, and chorismate pyruvate lyase, wherein said exogenous DNA sequences encoding chorismate pyruvate lyase, DAHP synthase, transketolase, and PEP synthase are transcribed from a first promoter (see claim 1 and 2). Ward also teaches that the DAHP can be from EC 4.1.2.15 (col 4, lines 10-20), and that industrial production of primary metabolites derived from chorismite deregulated mutant strains that lack feedback inhibition of one or more of the enzymes including E. coli strains having DAHP synthase feedback inhibition removed (i.e., feedback inhibition-resistant as in claim 1).
In the alternative, it would have been prima facie obvious to one of ordinary skill at the time of filing to use the method of Ward with a reasonable expectation of successfully producing pHBA from recombinant microorganism. One of ordinary skill would have been motivated to do so because Ward teaches that pHBA can be successfully produced using culturing techniques including recombinant microorganisms harboring exogenous DAHP synthase.
Regarding claim 48, Ward teaches including DNA sequences that code for chorismite pyruvate lyase (see claim 1, 2, 5, and 9).
Accordingly, the claimed invention was anticipated by, or in the alternative, rendered prima facie obvious by the teachings of Ward.
Claim Rejections - 35 USC § 103
First rejection
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Ward as applied to claims 1 and 48 above, in view of Ger et al (A single Ser-180 mutation desensitizes feedback inhibition of the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthetase in Escherichia coli. J Biochem. 1994 Nov;116(5):986-90).
As discussed above, Ward teaches a method for producing p-hydroxybenzoic acid biocatalytically in a microbial cell transformant via the common pathway of aromatic compounds synthesis where the cell has feedback inhibition removed.
Ward does not explicitly teach the feedback-inhibition resistant mutation is, inter alia, a substitution at position 180 of the wild-type amino acid sequence of DAHP synthase.
However, Ger teaches the enzyme 3-deoxy-D-arabino-heptulosonate 7-phosphate synthetase (DAHP synthetase, EC 4.1.2.15) catalyzes the first committed step in the biosynthesis of aromatic acids and vitamins (see pg. 986 col 1; abstract). Ger teaches that a DAHP synthetase enzyme resistant to feedback inhibition of phenylalanine would be critical to unraveling the mechanism of feedback inhibition as well as in attempting to overproduce aromatic amino acids through fermentation (see 986, col 1). Ger further teaches, inter alia, site-directed mutagenesis of serine at position 180 to phenylalanine, which resulted in a feedback-insensitive mutant with comparable enzymatic activity to the wildtype but decline of feedback inhibition from 60% to less than 10% Replacement of Ser-180 (abstract; see also pg. 989 col 1, paragraph 2).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Ward to include a DAHP mutant harboring a mutation at position 180 (such as SER-180 to Phe-180) as taught by Ger to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make the modification because Ger explicitly teaches that mutations such as Ser-180 to Phe-180 in DAHP synthase advantageously results in marked resistance to feedback inhibition.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary.
Second rejection
Claim(s) 5 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Ward as applied to claims 1 and 48 above, and further in view of Yukawa et al (WO2015174446A1).
As discussed above, the claims were anticipated, or in the alternative, rendered prima facie obvious by the teachings of Ward.
Ward does not explicitly teach the chorismate pyruvate lyase is P. rustigianii UbiC or comprises the amino acid sequence of SEQ ID NO: 4.
However, Yukawa teaches chorismite pyruvate lyase mutants useful for improving the production of 4-hydroxybenzoic acid (i.e., pHBA) (see abstract; claims). Yukawa explicitly teaches a transformant obtained by introducing a lyase from P. rustigianni (ubiC) into a host cell before culturing the transformant, and a sequence of chorismite pyruvate lyase that has 100% sequence identity to SEQ ID NO: 4 (as in claim 22; see alignment below):
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Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the method of Ward by including a chorismite pyruvate lyase for the production of pHBA as taught by Yukawa to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Yukawa teaches a chorismite pyruvate lyase and corresponding sequence capable of advantageously improving the production of 4-hydroxybenzoic acid when used in a recombinant host cell.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary.
Third rejection
Claim(s) 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Ward as applied to claims 1 and 48 above, and further in view of Choi et al (Multicopy integration and expression of heterologous genes in Methylobacterium extorquens ATCC 55366. Appl Environ Microbiol. 2006 Jan;72(1):753-9).
As discussed above, the claims were anticipated, or in the alternative, rendered prima facie obvious by the teachings of Ward.
Ward further teaches that the expression is driven by a single vector and can include at least one promoter (see, e.g., claim 1 and 2), including inducible promoters.
Ward does not explicitly teach the promoter is an M. extorquens methanol dehydrogenase promoter (Applicant’s elected species).
However, Choi teaches use of promoters from M. extorquens (see title, abstract). Choi teaches that Pmxaf promoter from M. extorquens is a strong homologous promoter for use in expression vectors (see pg. 755, col 2; see also Fig. 1). Choi teaches recombinant M. extorquens containing the methanol dehydrogenase promoter (PmxaF), which drives efficient production of heterologous proteins in the absence of selective pressure for maintenance of target genes (see pg. 758, col 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to modify the method of Ward by including the M. extorquens promoter as taught by Choi to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Choi explicitly teaches that the promoter is advantageously capable of driving efficient production of heterologous proteins in the absence of selective pressure for maintenance of target genes.
Regarding claim 8, Ward teaches the vector can contain multiple nucleic acid sequences (see claim 1 and 2).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary.
Fourth rejection
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Ward as applied to claims 1 and 48 above, and further in view of Nguyen et al. (Systematic metabolic engineering of Methylomicrobium alcaliphilum 20Z for 2,3-butanediol production from methane. Metab Eng. 2018 May;47:323-333).
As discussed above, the claims were anticipated, or in the alternative, rendered prima facie obvious by the teachings of Ward.
Ward does not explicitly teach wherein the recombinant microorganism is M. alcaliphilum 20Z.
However, Nguyen teaches M. alcaliphilum 20Z provides opportunities for metabolic engineering of the strain for production of industrially relevant products by integrating biosynthetic pathways for the production of a wide variety of chemicals (see pg. 323-324). Nguyen also teaches that the microbe can be used to express recombinant genes as well as have its culture conditions optimized for fed-batch stirred tank bioreactors (see abstract, throughout).,
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to modify the method of Ward by including the M. alcaliphilum 20Z as taught by Nguyen as the recombinant microorganism to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Nguyen teaches that the strain advantageously can be metabolically engineered for production of industrially relevant products by integrating biosynthetic pathways for the production of a wide variety of chemicals.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary.
Fifth rejection
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable Ward as applied to claims 1 and 48 above, and further in view of Yukawa and Groom et al (A Mutagenic Screen Identifies a TonB-Dependent Receptor Required for the Lanthanide Metal Switch in the Type I Methanotroph "Methylotuvimicrobium buryatense" 5GB1C. J Bacteriol. 2019 Jul 10;201(15):e00120-19).
As discussed above, the claims were anticipated, or in the alternative, rendered prima facie obvious by the teachings of Ward.
Ward does not explicitly teach the recombinant microorganism comprises a nucleic acid sequence encoding the polypeptide of SEQ ID NO: 4.
However, Yukawa teaches chorismite pyruvate lyase mutants useful for improving the production of 4-hydroxybenzoic acid (i.e., pHBA) (see abstract; claims). Yukawa explicitly teaches a transformant obtained by introducing a lyase from P. rustigianni (ubiC) into a host cell before culturing the transformant, and a DNA encoding the mutant chorismate-pyruvate lyase that encodes a polypeptide (see claim 3; see SEQ ID NO: 3) that has 100% sequence identity to SEQ ID NO: 4 (as in claim 22; see alignment below):
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Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the method of Ward by including a chorismite pyruvate lyase for the production of pHBA as taught by Yukawa to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Yukawa teaches a chorismite pyruvate lyase and corresponding sequence capable of advantageously improving the production of 4-hydroxybenzoic acid when used in a recombinant host cell.
Neither Ward nor Yukawa teaches a nucleic acid sequence set forth in SEQ ID NO: 6.
However, Groom teaches that metabolic enzymes in methanotrophic bacteria rely on metals for both their expression and their catalysis (see abstract). Groom teaches that M. buryatense is an excellent model for understanding the regulatory and uptake mechanisms of lanthanide metals in methanotrophs is critical to assess the microbiological impact on atmospheric methane levels and to apply these organisms to industrial bioproduction and biometallurgy (see pg. 2, paragraph 4). Groom further teaches selection of strains for the presence of the mxaF promoter and a nucleic acid sequence that has 100% sequence identity to SEQ ID NO: 6 (see alignment below).
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Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the method of Ward and Yukawa by including the nucleic acid sequence as disclosed by Groom to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Groom explicitly teaches a nucleic acid sequence that is used advantageously in M. buryatense, as an excellent model for understanding industrial bioproduction and biometallurgy.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill at the time of filing, especially in the absence of evidence to the contrary.
Claim Objections/Allowable Subject Matter
The examiner notes that after searching SEQ ID NO: 45 (see claim 16), the sequence has been deemed free of the prior art, as the prior art fails to teach or suggest the recombinant microorganism sequence.
Claim 16 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
US10443060B2
Ward et al (Genomic insights into methanotrophy: the complete genome sequence of Methylococcus capsulatus (Bath). PLoS Biol. 2004 Oct;2(10):e303.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672