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 1-12 are pending and under examination.
Priority
This application, filed on 4/11/2024, is a 371 of PCT/KR2022/009268 filed 6/28/2022, which claims priority to REPUBLIC OF KOREA 10-2021-0121930 filed 9/13/2021. For the prior art purposes, the effective filing date is June 28, 2022.
Information Disclosure Statement
The information disclosure statements filed on March 13, 2024; July 16, 2025 and October 31, 2025 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 1-2 and 6 are objected to because of the following informalities:
Claim 1 recites “one or more selected from … are inhibited” in the last line, which is ungrammatical and should be amended to recite “is inhibited”. Claim 1 is convoluted and redundant, and contains superfluous word “biosynthetic” in line 2. Claim 1 may be amended to:
A recombinant microorganism with controlled ability to produce polyol or exopolymer in a microorganism, with one or more inhibited pathways selected from the group consisting of:
a pathway that converts glucose-6-phosphate to exopolysaccharide,
a pathway that converts glycerophosphate to glycerol,
a pathway that converts acetoin to (2R,3S)-butanediol,
a pathway that converts acetoin to (2R,3R)-butanediol, and
a pathway that converts glutamic acid to polyglutamic acid.
Claim 2 recites “Bacillus” which does not follow the convention of reciting a genus in italics and should be corrected to recite “Bacillus”.
Claim 6 recites “an ability … are inhibited” in line 3, which is ungrammatical and should be amended to recite “is inhibited”.
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 1-12 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 “in that one or more selected from the group consisting of” in line 3. It is unclear whether the phrase is requiring “a recombinant microorganism” or “a biosynthetic pathway for polyol or exopolymer” to inhibit the group of alternative pathways.
Claims 2-12 are rejected for depending from rejected claim 1 but failing to remedy the indefiniteness therein.
Claim 7 recites “wherein the pathway that converts glucose-6-phosphate is inhibited, one of more selected from …” without placing a connecting word of “and” or “or” between “inhibited, one”, making it unclear how many pathways are required to be inhibited.
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 1-3, 6, 9 and 11-12 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Song et al. (“Microbial production of 2,3‑butanediol for industrial applications”, Journal of Industrial Microbiology & Biotechnology, 2019, Vol.46, Issue 11, pp.1583-1601).
Regarding claim 1, Song teaches that gram-positive bacteria belonging to Bacillus and Paenibacillus are capable of producing 2,3-Butanediol (2,3-BD) (p.1589, 2nd column last sentence – p.1590, 1st column top 2 lines). Song teaches that several strains including B. licheniformis and B. amlyloliquefaciens have shown good performance, and a newly isolated B. licheniformis strain 10-1-A could thermo-stably produce 115.7 g/L of 2,3-BD with high productivity and yield (p.1590, 1st column 1st paragraph). Song teaches that when the gdh gene was deleted, optically pure (2R,3S)-BD isomer can be produced with a titer of 90.1 g/L in B. licheniformis (p.1590, 1st column, 2nd paragraph). Song further teaches that B. subtilis can be engineered for production of (2R,3S)-BD, and systematic engineering strategies include inactivation of (2R,3R)-BD dehydrogenase (p.1590, 1st column 2nd paragraph).
Regarding claim 2, Song teaches engineered B. subtilis and B. licheniformis strains (p.1590, 1st column, 1st-2nd paragraphs).
Regarding claim 3, Song teaches production of (2R,3R)-butanediol and (2R,3S)-butanediol isomer (p.1590, 1st column 2nd paragraph).
Regarding claim 6, Song teaches most B. licheniformis and B. subtilis strains produce (2R,3R)-BD and (2R,3S)-BD at a close ratio of 1:1; however, when the budC gene was deleted, optically pure (2R,3R)-BD isomer can be produced in B. licheniformis with a titer of 123.7 g/L and when the gdh gene was deleted, optically pure (2R,3S)-BD isomer can be produced with a titer of 90.1 g/L in B. licheniformis (p.1590, 1st column, 2nd paragraph).
Regarding claim 9, Song teaches newly isolated B. licheniformis X10 strain possessing high tolerance to fermentation inhibitors such as furfural, vanillin, formic acid, and acetic acid was used for fed-batch fermentation and 74 g/L of 2,3-BD was produced from corn stover hydrolysate (i.e. a carbon source) with a productivity of 2.1 g/L/h (p.1592, 2nd column, last paragraph).
Regarding claim 11, Song teaches in S. marcescens a yield of 152 g/L of 2,3-BD with yield and productivity of 0.41 g/g·sucrose and 2.67 g/L/h (carbon source is sucrose) (p.1589, 2nd column 2nd paragraph).
Regarding claim 12, Song teaches most 2,3-BD-producing bacteria have optimal growth temperatures from 30 to 37°C (p.1594, 1st column, 1st full paragraph). Song further teaches thermophilic 2,3-BD-producing bacteria B. licheniformis has great potential for industrial production because this strain is GRAS classified and optimally grows at 50 to 60°C (p.1594, 1st column, 1st full paragraph).
Claims 1, 4-5 and 10 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Elsholz et al. (“Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase”, Genes & Development, 2014, Vol. 28, pp.1710-1720). The rejection of claims 1 and 5 are further evidenced by Song et al. (“Simultaneous and selective production of exopolymers and polyols by metabolically engineered Bacillus licheniformis strains”, Biochemical Engineering Journal, 2022, Vol. 181, Article 108381, 11 pages).
Regarding claim 1, Elsholz teaches gram-positive Bacillus subtilis is capable of forming biofilms, with cells in biofilms held together by an extracellular matrix consisting of amyloid-like fibers and exopolysaccharide (EPS) (p.1710, 2nd column). Elsholz teaches that the first two genes (epsA and epsB) of the 15-gene eps operon encode conserved two-component bacterial tyrosine kinases, that may function in the production of EPS (p.1711, 2nd column – 2nd full paragraph). Elsholz further teaches constructing single and double mutants of the two genes and tested their ability to form an extracellular matrix (p.1711, 2nd column – 2nd full paragraph). As evidenced by Song et al. 2022; tyrosine kinases are involved in the pathway that converts glucose-6-phosphate to exopolysaccharide (Figure 3). Thus, Elsholz teaches a recombinant microorganism with a pathway that converts glucose-6-phosphate to exopolysaccharide that is inhibited.
Regarding claim 4, Elsholz teaches gram-positive Bacillus subtilis is capable of forming biofilms, with cells in biofilms held together by an extracellular matrix consisting of amyloid-like fibers and exopolysaccharide (EPS) (p.1710, 2nd column).
Regarding claim 5, as evidenced by Song et al. (analysis of exopolysaccharide from B. licheniformis strain (4071)), EPS commonly contains glucose, galactose, glycerol, acetate and phosphate as monomers (p.6, 1st column 1st paragraph). Thus, the exopolysaccharide of Elsholz would necessarily contain at least one of glucose, galactose, phosphate and glycerol.
Regarding claim 10, Elsholz teaches B. subtilis cells were cultured from a 1-d-old colony in LB broth at 37°C (p.1717, 2nd column, Biofilm assay). Elsholz teaches the LB broth comprises tryptone and yeast extract (i.e. carbon sources) (p.1717, 1st column last paragraph).
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 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Elsholz et al. (“Self-regulation of exopolysaccharide production in Bacillus subtilis by a tyrosine kinase”, Genes & Development, 2014, Vol. 28, pp.1710-1720) as applied to claim 1 above, and further in view of Song et al. (“Microbial production of 2,3‑butanediol for industrial applications”, Journal of Industrial Microbiology & Biotechnology, 2019, Vol.46, Issue 11, pp.1583-1601).
The teachings of Elsholz et al. and Song et al. are discussed above.
Claim 7 is being interpreted to require that the pathway that converts glucose-6-phosphate to exopolysaccharide is inhibited AND the pathway that converts (2R,3R)-butanediol is inhibited.
Regarding claims 7 and 8, Elsholz teaches that the first two genes (epsA and epsB) of the 15-gene eps operon encode conserved two-component bacterial tyrosine kinases, that may function in the production of EPS (p.1711, 2nd column – 2nd full paragraph). Elsholz further teaches constructing single and double mutants of the two genes and tested their ability to form an extracellular matrix (p.1711, 2nd column – 2nd full paragraph). As evidenced by Song et al., tyrosine kinases are involved in the pathway that converts glucose-6-phosphate to exopolysaccharide (Figure 3).
Elsholz does not teach the production of (2R,3S)-butanediol.
Song teaches that B. subtilis can be engineered for production of (2R,3S)-BD, and systematic engineering strategies include inactivation of (2R,3R)-BD dehydrogenase (p.1590, 1st column 2nd paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the Bacillus subtilis strain taught by Elsholz to further inactivate the pathway of (2R,3R)-butanediol taught by Song to obtain a Bacillus subtilis strain that has the ability to simultaneously produce polyol and exopolymer. Each of Elsholz and Song teach recombinant Bacillus microorganisms genetically modified to inhibit a pathway. One of ordinary skill in the art would reasonably expect that combining a modification to increase exopolysaccharide production taught by Elsholz with a modification to increase production of (2R,3S)-butanediol taught by Song in the same recombinant bacterial host cell would predictably result in a single Bacillus that could produce both polyol (2R,3S)-butanediol and exopolysaccharide, because it would amount to a combination of known elements in a predictable way, and it was known in the art at the time of invention that Bacillus species could be modified to produce each of (2R,3R)-butanediol and exopolysaccharide.
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, 3-4, and 9-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 9, and 13 of copending Application No. 18/285,340 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims 1, 5, 9 and 13 anticipate the instant claims 1, 3-4, and 9-10.
Claim 1 of ‘340 is drawn to a recombinant microorganism for producing 2,3-butanediol, wherein the microorganism has a 2,3-butanediol biosynthetic pathway, wherein at least one selected from a group consisting of a polyglutamate biosynthetic pathway, a levan biosynthetic pathway, a lactate biosynthetic pathway, and a glycerol biosynthetic pathway is inhibited (relevant to instant claim 1).
Claim 7 of ‘340 is drawn to a recombinant microorganism for producing 2,3-butanediol of wherein the recombinant microorganism has a production ability of 2,3-butanediol higher than a production ability of 2,3-butanediol of a wild-type microorganism (relevant to instant claim 3).
Claim 9 of ‘340 is drawn to a recombinant microorganism for producing 2,3-butanediol of wherein at least one selected from a group consisting of a path for converting glutamate to polyglutamate, a path for converting sucrose to levan, a path for converting pyruvate to lactate, and a path for converting glycerophosphate to glycerol is inhibited (relevant to instant claim 4).
Claim 13 of ‘340 is drawn to a method for producing 2,3-butanediol, the method comprising: culturing the recombinant microorganism for producing 2,3-butanediol of claim 1; and recovering 2,3-butanediol from the culturing product (relevant to instant claims 9-10).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/DEEPA MISHRA/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657