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
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-5, 7 and 11-20 in the reply filed on October 3, 2024 is acknowledged. The traversal is on the grounds that claim 1 requires “the acetohydroxy acid isoreductase gene is kari gene” and “the microorganism is Escherichia coli”, and Hasegawa fails to teach those two features (See Remarks dated 10/3/2024, p.7 last paragraph to p.8 top paragraph). Applicant argues that the methods to improve the redox balance in present application differ from Hasegawa, because the application requires the kari gene and Hasegawa teaches the ilvC gene (See Remarks dated 10/3/2024, p.8 paragraphs 2-4). Applicant argues that the whole technical solution in the present application differ from Hasegawa, and Hasegawa fails to disclose a microorganism capable of producing L-valine by one-step anaerobic fermentation (See Remarks dated 10/3/2024, p.8 last 2 paragraphs). Applicant argues that Hasegawa teaches a two-step fermentation method, which is completely different from the one-step fermentation of the present application (See Remarks dated 10/3/2024, p.9 paragraph 3). Applicant argues that the microorganisms in the present application and Hasegawa are different; the present application uses Escherichia coli and Hasegawa uses Corynebacterium glutamicum (See Remarks dated 10/3/2024, last paragraph). Applicant argues that “the acetohydroxy acid isoreductase gene is kari gene” and “the microorganism is Escherichia coli” are special technical features shared by claims 1, 6, 8, 10 and 21, and therefore inventions I, II and III are so linked as to form a single general inventive concept (See Remarks dated 10/3/2024, p.11, 3rd paragraph).
This is not found persuasive because the features of “the acetohydroxy acid isoreductase gene is kari gene” and “the microorganism is Escherichia coli” were not in the previously presented claim set that was subject to restriction. In the currently pending claims, the common technical feature is “transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism”. However, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Park et al. (“Escherichia coli W as a New Platform Strain for the Enhanced Production of L-Valine by Systems Metabolic Engineering”, Biotechnology and Bioengineering, 2011, Vol. 108, Issue 5, pp.1140-1147).
Park teaches E. coli for the enhanced production of L-Valine (relevant to a recombinant microorganism for producing L-Valine) (title). Park teaches the ilvBNmut genes encoding feedback-resistant acetohydroxy acid synthase (AHAS) I and the L-valine biosynthetic ilvCED genes encoding acetohydroxy acid isomeroreductase, dihydroxy acid dehydratase, and branched chain amino acid aminotransferase, respectively were amplified by plasmid-based overexpression (relevant to transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism) (abstract). Park teaches the development of a metabolically engineered E. coli W strain for the enhanced biosynthesis of L-Valine (relevant to wherein the microorganism is E. coli) (p.1141, 1st column 2nd paragraph). Therefore, transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism is not a special technical feature that defines a contribution over the prior art. Thus, the claims lack unity of invention a posteriori.
The requirement is still deemed proper and is therefore made FINAL.
Claims 6, 8, 10, 17-19 and 21-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 3, 2024. It is noted that claims 17-19 and 21-26 are directed towards modifications that are different from or in addition to the single elected species of “enhancing activity of AHAS and/or ilvD”, and thus are drawn to non-elected species and withdrawn from further consideration.
Priority
This application is a 371 of PCT/CN2020/137780 filed on 12/18/2020, which claims priority to CHINA 202010401422.5 filed on 5/13/2020.
Information Disclosure Statement
The information disclosure statements filed on October 12, 2021; September 21, 2022; and September 25, 2024 all comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. All references were considered.
Claim Objections
Claims 1 and 4-5 are objected to because of the following informalities:
Claim 1 recites “transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism, so that enhancing the activity” in lines 2-4, which is ungrammatical. If applicant is suggesting that activity is enhanced by the transferring of the genes, perhaps the phrase can be amended to recite “into a microorganism, thereby enhancing the activity”.
Claim 1 recites “the leucine dehydrogenase gene is leuDH gene; the microorganism is Escherichia coli” in the last 2 lines, which is missing the conjunction “and” between the two clauses. It is suggested that the phrase be amended to recite “the leucine dehydrogenase gene is leuDH gene; and the microorganism is Escherichia coli”.
Claim 4 recites “or a RBS5 artificial regulatory element” in line 4, which uses the incorrect article “a”, and should be amended to recite “or an RBS5 artificial regulatory element”.
Claim 5 recites “integrated into a genome of the microorganism”, which is ungrammatical. As it is inherent to the microorganism that is has a genome, it is suggested the phrase be amended to recite “integrated into the genome of the microorganism”.
Appropriate correction is required.
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.
Claims 1-5, 7 and 15-16 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites a method comprising transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism “so that enhancing the activity” in line 4. It is unclear whether the “so that” is supposed to be modifying something else which is done to enhance activity, or if the activity is enhanced only by the transferring step. Claim 1 further recites “the leucine dehydrogenase gene is leuDH” in line 7-8, however there is no antecedent basis for “the leucine dehydrogenase gene”. Claim 1 recites “an amino acid dehydrogenase gene” in line 3, of which leucine dehydrogenase is a species. Perhaps applicant intended to recite “wherein the amino acid dehydrogenase gene is a leucine dehydrogenase gene leuDH”. Claim 1 further recites “wherein the acetohydroxy acid isoreductase gene and the amino acid dehydrogenase gene are NADH-dependent” in lines 6-7. However, it is unclear how the gene is NADH-dependent, as Figure 1 and the specification identify the enzymes (i.e. the gene product) as being NADH-dependent.
Claim 2 recites the phrase “preferably” in the last 2 lines. The phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear whether the word “preferably” is intended to indicate that the knocking out a gene msgA is only achieved by substituting the msgA gene with the ilvC gene, or if this is a single non-limiting example with numerous other options.
Claim 4 recites the limitation “an encoding gene of the enzyme” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 4 depends from claim 1, which recites “an acetohydroxy acid isoreductase gene” and “an amino acid dehydrogenase gene”. It is unclear whether “the enzyme” refers to the acetohydroxy acid isoreductase or the amino acid dehydrogenase, making the claim indefinite.
Claim 4 recites the phrase “preferably” in lines 3 and 5. The phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear whether the word “preferably” in line 3 is intended to indicate that the regulatory element is selected from MI-46 artificial regulatory element, MI-93 artificial regulatory element, and RBS5 artificial regulatory element or if these are non-limiting examples of regulatory elements with numerous other options. It is unclear whether the “preferably” in line 5 is intended to indicate that the MI-93 artificial regulatory element only regulates genes ilvD, leuDH, ilvBN and ilvGM, or if these are non-limiting examples of genes that can be regulated with numerous other options.
Claim 4 recites “the M1-37 artificial regulatory element” in line 7. There is insufficient antecedent basis for this limitation in the claim. There is no previous recitation of “an M1-37 artificial regulatory element” either in claim 4, nor in claim 1 from which claim 4 depends.
Claim 5 recites the limitation “the enzyme encoding gene” in lines 2-3, 5, 7 and 9. There is insufficient antecedent basis for this limitation in the claim. Claim 5 depends from claim 1, which recites “an acetohydroxy acid isoreductase gene” and “an amino acid dehydrogenase gene”. It is unclear whether “the enzyme” refers to the acetohydroxy acid isoreductase or the amino acid dehydrogenase, making the claim indefinite.
Claim 5 recites the phrase “preferably” in lines 5, 7 and 9. The phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear what function the word “preferably” is modifying in lines 5, 7 and 9. It is further unclear whether “a method of integrating into the genome of the microorganism” in line 5, “a homologous recombination method” in line 7, and “a two-step homologous recombination method” are able to accomplish any or all of “transfer, mutation, knockout, activation or regulation”, or if these are non-limiting examples of methods with numerous other options.
Regarding claim 7, The term “highly producing” in line 2 is a relative term which renders the claim indefinite. The term “highly producing” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what makes the production “high” compared to merely producing L-valine, and what metrics are required in determine whether “highly producing” is achieved.
Claim 15 recites the phrase “preferably” in line 3. The phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear whether the word “preferably” is intended to indicate that the ilvH gene is only enhanced by mutation, or if this is a non-limiting example of how the gene can be enhanced with numerous other options.
Claim 16 is rejected for depending from rejected claims 1 and 2 but failing to remedy the indefiniteness therein.
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.
Claims 1-5, 7 and 15-16 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims 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, at the time the application was filed, had possession of the claimed invention.
Applicant is referred to MPEP 2163(II)(A)(3)(a)(i and ii), which states that 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 applicant was in possession of the claimed genus. 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
Claims 1-5, 7 and 15-16 are drawn to a construction method of a recombinant microorganism for producing L-valine, comprising: transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism. Claim 2 requires one or more modifications “enhancing activity of AHAS and/or ilvD”. Claim 4 requires at least one regulatory element to activate or enhance activity of an encoding gene.
The current specification identifies the use of regulatory elements M1-46 artificial regulatory element, an M1-93 artificial regulatory element, or an RBS5 artificial regulatory element to control the enzyme encoding gene (specification p.4 last paragraph to p.5 top paragraph). The current specification describes a single condition of using the M1-93 artificial regulatory element to regulate the ilvD gene (specification p.7, 3rd sentence from bottom). While the specification provides written description for the regulatory element MI-93 as being used to activate or enhance activity of ilvD, the specification does not provide written description for other ways in which the gene is activated or enhanced. The scope of claim 1 encompasses other ways to activate and/or enhance the gene that are not described in the specification. The specification does not identify any other conditions that would activate and/or enhance activity of the encoding gene.
Yu et al. (“Resistance to AHAS inhibitor herbicides: current understanding”, Pest Management Science, 2013, Vol. 70, Issue 9, pp.1340-1350) states that acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6) is the first enzyme in the pathway for biosynthesis of branched-chain, essential amino acids valine, leucine and isoleucine (p.1340, 1st column 1st paragraph). Yu discusses that AHAS inhibition starves plants of valine, leucine and isoleucine, leading to plant death (p.1340, 1st column 1st paragraph). Yu further teaches that evolved resistance to AHAS inhibitor herbicides is due to single point mutations in the target AHAS gene that reduce AHAS sensitivity (p.1340, 1st column 1st paragraph), suggesting that enhancing activity of AHAS can be accomplished by single point mutations in the gene and does not require specific regulatory elements.
Based on the teaching of the prior art, the activity of AHAS can be affected by mutations in the gene. The single description in the specification of using an M1-93 artificial regulatory element to regulate an encoding gene ilvC is not sufficient to show possession of a generic method that requires knowledge of all the methods of activating or enhancing gene activity. For these reasons, claims 1-5, 7 and 15-16 fail to comply with the written description requirement.
Claim Rejections - 35 USC § 102
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.
Claims 1-2, 5 and 15-16 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Park et al. (“Escherichia coli W as a New Platform Strain for the Enhanced Production of L-Valine by Systems Metabolic Engineering”, Biotechnology and Bioengineering, 2011, Vol. 108, Issue 5, pp.1140-1147). Claim 1 is further evidenced by Liu et al. (“Molecular evolution of acetohydroxyacid synthase in bacteria”, 2017, Vol.6, Issue 6, article e00524, 14 pages) and Brenda Enzymes (information on EC 1.1.1.86, ketol-acid reductoisomerase (NADP+), https://www.brenda-enzymes.org/enzyme.php?ecno=1.1.1.86)
Regarding claims 1-2 and 16, the limitation “the acetohydroxy acid isoreductase gene and the amino acid dehydrogenase gene are NADH-dependent” is being interpreted as the “acetohydroxy acid isoreductase” and the “amino acid dehydrogenase” enzymes are NADH-dependent. The phrase “so that” is being interpreted as “thereby”, so transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism “thereby” results in enhancing the activity of the genes.
Park teaches E. coli for the enhanced production of L-Valine (relevant to a recombinant microorganism for producing L-Valine) (title). Park teaches the ilvBNmut genes encoding feedback-resistant acetohydroxy acid synthase (AHAS) I and the L-valine biosynthetic ilvCED genes encoding acetohydroxy acid isomeroreductase, dihydroxy acid dehydratase, and branched chain amino acid aminotransferase, respectively were amplified by plasmid-based overexpression (relevant to transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism) (abstract). Park teaches that following chromosomal manipulation of E. coli W, the L-valine biosynthetic genes were overexpressed; and the isoenzyme AHAS I, encoded by ilvBN, needed the ilvBN operon to be overexpressed and the feedback inhibition of AHAS I to be removed; thus the plasmid pKBRilvBNmutCED, which contains the feedback-resistant AHAS I was employed (relevant to claims 2 and 16: wherein the method further comprises enhancing activity of AHAS) (p.1144, 1st column last paragraph). Park teaches the development of a metabolically engineered E. coli W strain for the enhanced biosynthesis of L-Valine (relevant to wherein the microorganism is E. coli) (p.1141, 1st column 2nd paragraph).
The specification identifies acetohydroxy acid isoreductase as ilvC or KARI (p.4, 3rd paragraph from bottom). As evidenced by Brenda Enzymes, synonyms for acetohydroxy acid isoreductase include acetohydroxy acid isomeroreductase, ilvC, KARI (Synonym table), and therefore Park’s teaching of ilvBNmut and ilvCED genes encoding acetohydroxy acid isomeroreductase and branched chain amino acid aminotransferase teach the required enzymes of acetohydroxy acid isoreductase and an amino acid dehydrogenase.
Park is silent as to whether the acetohydroxy acid isoreductase and the amino acid dehydrogenase are NADH-dependent. However, as evidenced by Liu et al., acetohydroxyacid synthase is a key enzyme in metabolic pathways leading to the synthesis of branched chain amino acids (FIG.1). Thus, the enzymes taught by Park are NADH-dependent enzymes.
Regarding claim 5, Park teaches the plasmid pTrc184ygaZHlrp over-expressing the L-valine exporter ygaZH and global regulator leucine responsive protein (Lrp) was transformed into the WLA strain (relevant to wherein a plasmid containing the enzyme encoding gene is transferred into the microorganism) (p.1144, 1st column last paragraph).
Regarding claim 15, Park teaches the ilvBNmut genes encoding feedback-resistant acetohydroxy acid synthase (AHAS) I (relevant to wherein the AHAS is ilvBN) (abstract).
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, 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 3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Escherichia coli W as a New Platform Strain for the Enhanced Production of L-Valine by Systems Metabolic Engineering”, Biotechnology and Bioengineering, 2011, Vol. 108, Issue 5, pp.1140-1147) as applied to claim 1 above, and further in view of Jarboe et al. (“Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology”, Journal of Biomedicine and Biotechnology, 2010, Article ID 761042, 18 pages).
The teachings of Park et al. are discussed above.
Regarding claim 3, Park teaches the microorganism is E. coli W ATCC 9637 (p.1141, Table 1).
Park does not teach wherein the microorganism is Escherichia coli ATCC 8739.
However, Jarboe teaches that E. coli are an excellent chassis for synthetic biology (p.2, 2nd column last paragraph). Jarboe further teaches that E. coli has been used as a model organism since the beginning of genetic engineering, including K-12 strain, B (ATCC# 11303), C (ATCC# 8739), and W (ATCC# 9637) that are also generally regarded as safe since they are unable to colonize the human gut (relevant to wherein the microorganism is Escherichia coli ATCC 8739) (p.2, 2nd column last paragraph – p.3 1st column top paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microorganism taught by Park by replacing the E. coli strain W taught by Park with E. coli strain C (ATCC# 8739) taught by Jarboe, because Jarboe teaches that these strains are generally regarded as safe since they are unable to colonize the human gut. One of ordinary skill in the art would reasonably expect that replacing one known strain of E. coli with another would predictably result in a recombinant microorganism for producing L-valine, because it was known in the art at the time of invention that E. coli strain W and E. coli ATCC 8739 were equivalent strains for synthetic biology applications.
Regarding claim 7, Park does not teach acquiring a recombinant microorganism through metabolic evolution.
However, Jarboe teaches metabolic evolution provides an excellent alternative method for strain improvement, through which reactions that are not currently predictable would be selected to improve biocatalyst performance (p.7, 1st column 1st paragraph). Jarboe teaches metabolic evolution for improving L-alanine production in E. coli (p.7, Figure 3). Jarboe teaches using metabolic evolution to further improve cell growth and D-lactate productivity in E. coli strain W3110 after redesigning central metabolism (relevant to acquiring a recombinant microorganism through metabolic evolution) (p.10, 1st column 1st paragraph). Jarboe teaches that the final D-lactate producing strain could convert 12% (w/v) glucose to 118 g/L D-lactate with an excellent yield (98%) and productivity (2.88 g/L/h) (relevant to highly producing) (p.10, 1st column 1st paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microorganism of Park to use metabolic evolution taught by Jarboe to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to do so because Jarboe teaches that metabolic evolution further improves cell growth and productivity. One of ordinary skill in the art would have found it beneficial to use metabolic evolution to obtain a strain that had increased yield and productivity of L-valine, and it was known in the art at the time of invention that metabolic engineering could be used to obtain strains with improved productivity.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Escherichia coli W as a New Platform Strain for the Enhanced Production of L-Valine by Systems Metabolic Engineering”, Biotechnology and Bioengineering, 2011, Vol. 108, Issue 5, pp.1140-1147) as applied to claim 1 above, and further in view of Zhang et al. (US 2016/0068882 A1, published on March 10, 2016).
The teachings of Park et al. are discussed above.
Regarding claim 4, Park teaches the plasmid pTrc184ygaZHlrp over-expressing the L-valine exporter ygaZH and global regulator leucine responsive protein (Lrp) was transformed into the WLA strain (relevant to wherein at least one regulatory element is used to activate or enhance activity of an encoding gene of the enzyme) (p.1144, 1st column last paragraph).
Park does not teach wherein the regulatory element is selected from M1-46 artificial regulatory element or M1-93 artificial regulatory element.
However, Zhang teaches a method for constructing recombinant microorganism (title). Zhang teaches that the method for improving the enzymatic activity of α-ketoglutarate dehydrogenase in E. coli or a mutant thereof is replacing original regulatory part of α-ketoglutarate dehydrogenase gene, sucAB, in E. coli or a mutant thereof with any of following regulatory parts: artificial regulatory parts M1-46, M1-37 and M1-93 (relevant to wherein the regulatory element is selected from an M1-46 artificial regulatory element or an M1-93 artificial regulatory element) (description p.2, [0014]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the microorganism of Park by replacing the global regulator leucine responsive protein (Lrp) with artificial regulatory parts M1-46 or M1-93 taught by Zhang to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to do so because Zhang teaches that a method for improving the enzymatic activity of the dehydrogenase in E. coli is by replacing the original regulatory part with an artificial regulatory part M1-46 or M1-93. One of ordinary skill in the art would have found it beneficial to use a regulatory element taught by Zhang to improve the enzymatic activity of the desired enzyme in E. coli.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7 and 15-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 14, 18 and 24 of copending Application No. 17/604,770 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims anticipate the instant claims.
Instant claim 1 is drawn to a construction method of a recombinant microorganism for producing L-valine, comprising: transferring an acetohydroxy acid isoreductase gene and an amino acid dehydrogenase gene into a microorganism.
Claim 1 of ‘770 is drawn to a construction method of a recombinant microorganism for producing L-valine comprising: transferring an amino acid dehydrogenase gene into a microorganism and/or activating an Entner-Doudoroff metabolic pathway in the microorganism; the amino acid dehydrogenase gene is NADH-dependent; the microorganism is Escherichia coli.
Claim 2 of ‘770 is drawn to the method of claim 1, wherein the method further comprises one or more of the following modifications:
(7) enhancing activity of AHAS and/or ilvD (anticipates instant claim 2).
Claim 3 of ‘770 is drawn to the method of claim 1, wherein the microorganism is Escherichia coli ATCC 8739 (anticipates instant claim 3).
Claim 4 of ‘770 is drawn to the method of claim 1, wherein at least one regulatory element is used to activate or enhance activity of encoding genes ilvD, leuDH, ilvBN, zwf, pgl, ilvGM, edd, eda or ilvC (anticipates instant claim 4, instant claim 15).
Claim 5 of ‘770 is drawn to the method of claim 1, wherein one or more copies of the enzyme encoding gene and the regulatory element are integrated into a genome of the microorganism, or a plasmid containing the enzyme encoding gene is transferred into the microorganism (anticipates instant claim 5).
Claim 7 of ‘770 is drawn to the method of claim 1, wherein the construction method further comprises acquiring a recombinant microorganism for producing L-valine obtained through metabolic evolution on the basis of the recombinant microorganism obtained by the construction method according to claim 1 (anticipates instant claim 7).
Claim 14 of ‘770 is drawn to the method of claim 1, wherein the amino acid dehydrogenase gene is a leucine dehydrogenase gene (anticipates instant claim 1).
Claim 18 of ‘770 is drawn to the method of claim 2, wherein the item (7) is selected for modification (anticipates instant claim 16).
Claim 24 of ‘770 is drawn to the method of claim 4, wherein the regulatory element is selected from an M1-93 artificial regulatory element, an MRS1 artificial regulatory element, a RBS artificial regulatory element or an M1-46 artificial regulatory element (anticipates instant claim 4).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEEPA MISHRA whose telephone number is (571) 272-6464. The examiner can normally be reached Monday - Friday 7:30am - 5:30pm EST.
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/DEEPA MISHRA/ Examiner, Art Unit 1657
/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636