DETAILED ACTION
Status of the Application
Claims 1-13 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment of claims 1-2, 6-8 as submitted in a communication filed on 7/17/2026 is acknowledged.
Applicant elected without traverse of Group I, claims 1-12, drawn in part to a recombinant microorganism for producing 2,3-butanediol, wherein said recombinant microorganism has at least one biosynthetic pathway inhibited, wherein said biosynthetic pathway is a polyglutamate biosynthetic pathway, in a communication filed on 3/11/2026 is acknowledged.
In view of Applicant’s election of a polyglutamate biosynthetic pathway, claims 3-5, 9-12 are drawn to a non-elected invention. Claims 3-5, 9-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 3/11/2026.
Claims 1-2 and 6-8 are at issue and will be examined to the extent they encompass the elected invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/31/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 1-2, 6-8 remain 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 pre-AIA the applicant regards as the invention. New grounds of rejection are necessitated by amendment.
Claim 1 (claims 2, 6-8 dependent thereon) is indefinite in the recitation of “by deleting at least one corresponding endogenous gene selected from the group consisting of pgsBCAE…and dgp, respectively” for the following reasons. It is unclear as to how the term “corresponding” limits the claim. As written, one cannot determine if the term “corresponding” implies that the endogenous genes to be deleted are genes like pgsBCAE, sacB, ldh, or dgp, or if the endogenous genes to be deleted are selected from the group consisting of pgsBCAE, sacB, ldh, and dgp. In addition, it is unclear as to how the term “respectively” further limits the claim. For examination purposes, no patentable weight will be given to the terms “corresponding” and “respectively”. Correction is required.
Claim 6 is indefinite in the recitation of “…is lower than a production of the viscous polymer….when cultivating a corresponding wild type microorganism” for the following reasons. The claim as amended now requires the recombinant microorganism to be a B. licheniformis. The term “a corresponding wild type microorganism” encompasses a genus of microorganisms of any species. Moreover, even if the argument is made that the wild type microorganism is a B. licheniformis, the recitation of “a corresponding”, implies a genus of “corresponding” microorganisms which may be any B. licheniformis such that the comparison is made with, for example, B. licheniformis strain A, B. licheniformis strain B, or B. licheniformis strain C. The basis for comparison is variable, thus making the determination as to what is included or excluded from the scope of the claims impossible. For example, a recombinant microorganism can be included by the claim if the comparison is made with B. licheniformis strain A and excluded if the comparison is made with B. licheniformis strain B. The same recombinant microorganism can be simultaneously included and excluded from the scope of the claim depending on the wild type microorganisms used for comparison. For examination purposes, claim 6 will be interpreted as a duplicate of claim 1. Correction is required.
Claim 7 is indefinite in the recitation of “…production ability of…higher than a production ability of…of a wild-type Bacillus licheniformis microorganism from which the recombinant microorganism is derived” for the following reasons. If a microorganism is derived from another microorganism, this implies any number of modifications from the “another”. As such, the term “a wild type Bacillus licheniformis” encompasses a genus of Bacillus licheniformis microorganisms because one could arrive to the same recombinant microorganism by genetically modifying any wild type Bacillus licheniformis. The basis for comparison is variable, thus making the determination as to what is included or excluded from the scope of the claims impossible. For example, a recombinant microorganism can be included by the claim if the comparison is made with wild type Bacillus licheniformis strain A and excluded if the comparison is made with wild type Bacillus licheniformis strain B. The same recombinant microorganism can be simultaneously included and excluded from the scope of the claim depending on the wild type microorganisms used for comparison. For examination purposes, claim 7 will be interpreted as a duplicate of claim 1. Correction is required.
Claim 8 is indefinite in the recitation of “wherein a polyglutamate biosynthetic pathway for converting glutamate to…is inhibited while a levan biosynthetic pathway for converting…, a lactate biosynthetic pathway for converting….and a glycerol biosynthetic pathway for converting …are not inhibited” for the following reasons. As written, it is unclear if “a polyglutamate biosynthetic pathway for converting glutamate to polyglutamate” is the same polyglutamate biosynthetic pathway of claim 1. Similarly, it is unclear if “a levan biosynthetic pathway for converting sucrose to levan” is the same levan biosynthetic pathway” of claim 1, “a lactate biosynthetic pathway for converting pyruvate to lactate” is the same lactate biosynthetic pathway of claim 1, and “a glycerol biosynthetic pathway for converting glycerophosphate to glycerol” is the same glycerol biosynthetic pathway of claim 1. Moreover, it is unclear if the claim is further limiting the biosynthetic pathways recited in claim 1 so that the polyglutamate biosynthetic pathway is one for the conversion of glutamate to polyglutamate, the levan biosynthetic pathway is one for the conversion of sucrose to levan, the lactate biosynthetic pathway is one for the conversion of pyruvate to lactate, and the glycerol biosynthetic pathway is one for the conversion of glycerophosphate to glycerol. For examination purposes, it will be assumed that claim 8 is a duplicate of claim 1. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 1-2, 6-8 remain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 1 has been amended to recite a B. licheniformis microorganism in which the recited byproduct is inhibited by deleting at least one corresponding endogenous gene selected from the group consisting of pgsBCAE, sacB, ldh, and dgp, respectively. Applicant states that the specification discloses that the microorganism is most preferably a B. licheniformis microorganism and that the specification discloses deletion of the pgsBCAE gene to inhibit the conversion of glutamate to polyglutamate, deletion of the sacB gene to inhibit conversion of sucrose to levan, deleting the ldh gene to inhibit conversion of pyruvate to lactate and deletion of dgp to inhibit the conversion of glycophosphate to glycerol. Applicant states that these deletions were reduced to practice in the working examples.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to the claims as well as the teachings of the specification. While it is agreed that the specification discloses deletion of the pgsBCAE genes to inhibit the conversion of glutamate to polyglutamate, deletion of the sacB gene to inhibit conversion of sucrose to levan, deletion of the ldh gene to inhibit conversion of pyruvate to lactate and deletion of the dgp gene to inhibit the conversion of glycophosphate to glycerol, the claims as written/interpreted still encompass, for example a B. licheniformis microorganism having an inhibited polyglutamate biosynthetic pathway by any means and a deletion in the endogenous dgp gene. Similarly, the claims as written/interpreted still encompass a B. licheniformis microorganism having an inhibited levan biosynthetic pathway, a lactate biosynthetic pathway and/or a glycerol biosynthetic pathway inhibited by any means, and a deletion in the endogenous pgsBCAE genes. The claims do not recite “ wherein the polyglutamate biosynthetic pathway is inhibited by deleting at least the endogenous pgsBCAE genes, wherein the levan biosynthetic pathway is inhibited by deleting at least the endogenous sacB gene, wherein the lactate biosynthetic pathway is inhibited by deleting at least the endogenous ldh gene, and wherein the glycerol biosynthetic pathway is inhibited by deleting at least the endogenous dgp gene”.
The claims still require any method to inhibit the recited biosynthetic pathways beyond disruption of a gene associated with said biosynthesis. These additional methods include, for example, the use of inhibitors of expression, the expression of proteins that can act as inhibitors of transcription, antisense molecules to block the expression of a gene, or structural modifications to the coding region or the promoter region of a gene to alter the activity of the protein encoded by said gene. No structure/identity has been provided for any compound, protein or antisense molecule that could be used as an inhibitor of expression of any gene associated with the biosynthesis of polyglutamate, levan, glycerol or lactate in B. licheniformis. Therefore, for the reasons of record and those set forth above, one cannot reasonably conclude that the claimed invention is adequately described by the teachings of the specification and/or the prior art.
Claims 1-2, 6-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a B. licheniformis cell having a polyglutamate biosynthetic pathway inhibited by a deletion in the endogenous pgsBCAE genes, does not reasonably provide enablement for a recombinant B. licheniformis microorganism that has been modified by any means to inhibit any polyglutamate biosynthetic pathway, any levan biosynthetic pathway, any lactate biosynthetic pathway, and/or any glycerol biosynthetic pathway by any means. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant states that as amended, the claims are commensurate in scope with what the Office acknowledged to be enabled. Applicant states that amended claim 1 is limited to a recombinant B. licheniformis and to inhibition effected by deletion of the corresponding endogenous genes selected from pgsBCAE, sacB, ldh, and dgp. Applicant states that the specification provides working examples directed to the claimed feature. Applicant concludes that because the amendments remove the broad “any microorganism/any means” scope, no undue experimentation is required to practice the claimed invention.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to the claims as well as the teachings of the specification. While its agreed that limiting the microorganism to B. licheniformis addresses one of the grounds of rejection previously raised, the amendments made do not address other grounds of rejection previously raised. The Examiner acknowledges that the specification discloses deletion of the pgsBCAE genes to inhibit the conversion of glutamate to polyglutamate, deletion of the sacB gene to inhibit conversion of sucrose to levan, deletion of the ldh gene to inhibit conversion of pyruvate to lactate and deletion of the dgp gene to inhibit the conversion of glycophosphate to glycerol. However, the claims as written/interpreted still encompass, for example a B. licheniformis microorganism having an inhibited polyglutamate biosynthetic pathway by any means and a deletion in the endogenous dgp gene. Similarly, the claims as written/interpreted still encompass a B. licheniformis microorganism having an inhibited levan biosynthetic pathway, a lactate biosynthetic pathway and/or a glycerol biosynthetic pathway inhibited by any means, and a deletion in the endogenous pgsBCAE genes. It is reiterated herein that the claims do not recite “ wherein the polyglutamate biosynthetic pathway is inhibited by deleting at least the endogenous pgsBCAE genes, wherein the levan biosynthetic pathway is inhibited by deleting at least the endogenous sacB gene, wherein the lactate biosynthetic pathway is inhibited by deleting at least the endogenous ldh gene, and wherein the glycerol biosynthetic pathway is inhibited by deleting at least the endogenous dgp gene”. Thus, the claims still require any method to inhibit the recited biosynthetic pathways beyond disruption of a gene associated with said biosynthesis. These additional methods include, for example, the use of inhibitors of expression, the expression of proteins that can act as inhibitors of transcription, antisense molecules to block the expression of a gene, or structural modifications to the coding region or the promoter region of a gene to alter the activity of the protein encoded by said gene. No structure/identity has been provided for any compound, protein or antisense molecule that could be used as an inhibitor of expression of any gene associated with the biosynthesis of polyglutamate, levan, glycerol or lactate in B. licheniformis.
It was not routine in the art to screen by a trial and error process for (i) an essentially infinite number of genes to find those associated with the biosynthesis of the recited metabolite, and (ii) an essentially infinite number of genetic modifications, compounds, proteins and antisense molecules to find those that can achieve the desired inhibition. Therefore, for the reasons of record and those set forth above, one cannot reasonably conclude that the full scope of the claimed invention is enabled by the teachings of the specification and/or the prior art.
Claim Rejections - 35 USC § 102 (AIA )
Claims 1-2, 6-8 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Feng et al. (FEMS Microbiology Letters 362(11) fnv079, pages 1-7, 2015) as evidenced by Ji et al. (Biotechnology Advances 29:351-364, 2011; cited in the IDS) and Cao et al. (Bioresource Technology 102:4251-4257, 2011).
In view of the amendments made to claim 1, which now require the recombinant microorganism to be a B. licheniformis microorganism, and the fact that Feng et al. do not teach a recombinant B. licheniformis microorganism, this rejection is hereby withdrawn.
Claim Rejections - 35 USC § 103 (AIA )
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 of this title, 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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Ge et al. (Green Chemistry 18:4693-4703, 2016) in view of Song et al. (Journal of Industrial Microbiology & Biotechnology 47:97-108, published online 11/22/2019), Cromwick et al. (Biotechnology and Bioengineering 50:222-227, 1996), and Liu et al. (Journal of Applied Microbiology 128:1390-1399, 5/1/2020). This rejection is necessitated by amendment.
Ge et al. teach the production of 2,3-butanediol from B. licheniformis (Abstract). Ge et al. teach that while several hosts have been found to produce 2,3-BD, these hosts are pathogenic and produce a mixture of 2,3-BD stereoisomers, whereas B. licheniformis is a GRAS microorganism (nonpathogenic) that can produce high levels of 2,3-BD from glucose which is limited only to meso 2,3-BD and (2R,3R)-2,3-BD (page 4696, right column, Results).
Song et al. teach the production of 2,3-butanediol from a B. licheniformis strain that has been UV-mutated to reduce its mucoid forming characteristics (Abstract). Song et al. teach that B. licheniformis is a promising industrial host because a genetic toolbox for gene manipulation in this organism is available and its fermentation conditions are favorable for industrial operation. Song et al. teach that the endogenous mucoid formation of this microorganism is not desirable because it can hinder effective genetic manipulation of this microorganism (page 98, left column). Song et al. teach that genetic modifications that would result in increased production of 2,3- butanediol are highly desirable and that the mucoid-free strain was amenable for genetic manipulation and also showed enhanced 2,3-BDO production capabilities (page 98, left column, last paragraph). Song et al. teach that the thermophilic characteristics of B. licheniformis have advantages such as minimal contamination risks and low consumption of energy for cooling the fermentation vessel. Song et al. teach that its high cultivation temperature enables efficient simultaneous saccharification and fermentation of starch to produce 2,3-BDO.
Cromwick et al. teach that B. licheniformis naturally produces γ-polyglutamic acid (γ-PGA) which is secreted to the growth medium (page 222, right column, lines 1-3) and high mucoid colonies associated with high γ-PGA production (page 223, left column, first full paragraph). Cromwick et al. teach that since γ-PGA is an extracellular polymer, the culture medium becomes highly viscous with polymer production (page 222, right column, first full paragraph).
Liu et al. teach that B. licheniformis is a glutamate independent γ-PGA producer and that the pgsBCAE operon encodes the poly-γ-glutamic acid synthase required for the production of γ-PGA from glutamate (page 1391, left column, first full paragraph).
Claims 1-2, 6-8 as interpreted are directed in part to a recombinant B. licheniformis microorganism that has a 2,3-butanediol biosynthetic pathway, wherein said recombinant microorganism has a polyglutamate biosynthetic pathway which has been inhibited by a deletion in the endogenous pgsBCAE genes. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify a B. licheniformis cell such as that of Ge et al. to disrupt the endogenous pgsBCAE genes and inhibit the formation of γ-polyglutamic acid (polyglutamate). A person of ordinary skill in the art is motivated to disrupt the endogenous pgsBCAE genes and inhibit the formation of γ- polyglutamic acid because (a) γ- polyglutamic acid is associated with mucoid formation, which is undesirable for genetic modification of B. licheniformis, (b) reduction in mucoid formation was found to increase the formation of 2,3-BDO, and (c) γ-polyglutamic acid increases the viscosity of the culture medium, thus potentially interfering with the recovery of 2,3-BDO and/or increasing the energy required for mixing the culture medium. One of ordinary skill in the art has a reasonable expectation of success at deleting the endogenous pgsBCAE genes because the molecular biology techniques required to delete a gene are well known in the art as evidenced by Song et al. One of ordinary skill in the art has a reasonable expectation of success at observing a reduction in mucoid formation because Liu et al. teach that these genes encode the enzyme responsible for the formation of γ- polyglutamic acid from glutamate and Cromwick et al. teach the association between mucoid formation and γ-polyglutamic acid synthesis. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Applicant is advised that any Internet email communication by the Examiner has to be authorized by Applicant in written form. See MPEP § 502.03 (II). Without a written authorization by Applicant in place, the USPTO will not respond via Internet email to any Internet correspondence which contains information subject to the confidentiality requirement as set forth in 35 U.S.C. 122. Sample written authorization language can be found in MPEP § 502.03 (II). An Authorization for Internet Communications in a Patent Application or Request to Withdraw Authorization for Internet Communications form (SB/439) can be found at https://www.uspto.gov/patent/forms/ forms-patent-applications-filed-or-after-september-16-2012, which can be electronically filed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
September 18, 2026
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