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 1-4, 7 and 10 and the species of AlsS and AlsD in the reply filed on 07/10/2026 is acknowledged.
Claims 5-6 and 8-9 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/10/2026.
Priority
The instant application claims benefit to Application No. KR10-2023-0025311, filed 02/24/2023 and is acknowledged. The instant claims herein are examined using the effective filing date of 02/24/2023 for the basis of any prior art rejections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 02/23/2024 was properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) was considered.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg. 17. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 2 objected to because of the following informalities: claim 2 recites “wherein the nucleic acid construct comprises a gene encoding an enzyme, which synthesizes acetoin from pyruvate, as the first gene and a gene encoding an enzyme, which synthesizes 2,3-butanediol from acetoin, as a second gene.” The use of the commas after the terms “enzyme” and “pyruvate” and “acetoin” make the claim difficult to read. The examiner suggests removing the commas, so the claim reads, e.g., “wherein the nucleic acid construct comprises a gene encoding an enzyme which synthesizes acetoin from pyruvate as the first gene, and a gene encoding an enzyme which synthesizes 2,3-butanediol from acetoin as a second gene.” Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 7, and 10 rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (a natural product) without significantly more. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
Step 1 (Statutory Category): This part of the eligibility analysis evaluates whether the
claims fall within any statutory category. Here, the claims recite a nucleic acid construct comprising first and second genes, of which expressions are regulated by one promoter, wherein the first gene is located upstream of the second gene, the promoter is located upstream of the first gene, and an E. coli-derived Rho- independent terminator is located at the 3'-end of the first gene. This is a composition, therefore the claims fall within a statutory category of invention. [Step 1: YES]
Step 2A (Judicial Exceptions), Prong 1: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. A claim “recites” a judicial exception when the exception is “set forth” or “described” in the claim (see MPEP 2106.04(II)). Because the claim recites a nature-based product limitation, the markedly different characteristics analysis is used to determine if the nature-based product limitations are a product of nature exception (see MPEP 2106.04(c)(I)). This analysis is performed by comparing the nature-based product limitations in the claims to its naturally occurring counterparts to determine if it has markedly different characteristics (see MPEP 2106.04(c)(II). The claim recites at least one judicial exception. The claims broadly recite a nucleic acid construct including 2 genes, a promoter, and a rho-independent terminator at the 3’-end of the first gene and the examiner is interpreting the claims to require any 2 genes, a promoter, and a rho-independent terminator at the 3’-end of the first gene. The appropriate natural counterpart to the claimed nucleic acid construct is the same one as found in nature (i.e., two genes, a promoter, and a rho-independent terminator) and microorganism containing the nucleic acid construct.
Postle et al (A bidirectional rho-independent transcription terminator between the E. coli tonB gene and an opposing gene Cell, 41, 577-585) evidences a nucleic acid/gene construct found in E. coli containing tonB gene adjacent to a P14 gene. The intercistronic region between the two genes contains a rho-independent transcription terminator at the 3’ end of tonB and a promoter that functions bi-directionally in vivo and in vitro (see abstract; throughout). Please note that the broadest reasonable interpretation of the claims encompasses the naturally occurring intercistronic region of the E. coli of Postle. As such, the claims do not recite any markedly different characteristics to the naturally occurring nucleic acid construct.
Thus, the claim recites at least one judicial exception, a natural product. [Step 2A, Prong 1: YES]
Therefore, the analysis proceeds to Step 2A Prong 2.
Step 2A (Judicial Exceptions), Prong 2: This part of the eligibility analysis evaluates whether the claims as a whole integrate the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claims beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claims as a whole integrate the exception into a practical application. Claim 1 is limited to only the judicial exception. A judicial exception cannot form the basis for integration, so it cannot be considered to integrate the natural phenomena into a practical application. See MPEP 2106.04(d) III, which states that “Because a judicial exception alone is not eligible subject matter, if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application.” [Step 2A, Prong 2: NO]
Step 2B (Significantly More): This part of the eligibility analysis evaluates whether the claims as a whole amount to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05). This is based on an additional consideration of whether the elements in addition to the judicial exception add beyond what was well-understood, routine, and conventional to the claims. None of the claims at issue recite anything beyond the judicial exception or that amounts to significantly more than the recited exception. [STEP 2B: NO]
In view of the above, the claims are considered to be directed to the judicial exception without integration into a practical application, or adding significantly more to the claim over the judicial exception. Therefore, the claims do not qualify as eligible subject matter under 35 USC § 101.
Claim Rejections - 35 USC § 102
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.
Claims 1, 7, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Postle et al (A bidirectional rho-independent transcription terminator between the E. coli tonB gene and an opposing gene Cell, 41, 577-585).
Postle teaches a nucleic acid/gene construct found in E. coli containing tonB gene adjacent to a P14 gene. The intercistronic region between the two genes contains a novel rho-independent transcription terminator at the 3’ end of tonB that functions bi-directionally in vivo and in vitro and has similar efficiency in either orientation and has a relatively high efficiency of termination (see abstract; throughout; see pg. 582, col 1, paragraph 2-3). Postle also teaches a plasmid construct pWu5 containing tonB and P14 genes (a first and second gene as instantly claimed), the rho-independent terminator at the 3’-end of the tonB gene (a rho-independent terminator at the 3’-end of the first gene as in claim 1), and an E. coli trp promoter in vitro in E. coli K12 strains (a microorganism comprising the nucleic acid as in claim 7; E. coli as in claim 10; see Fig.1 , see pg. 577, col 2; see pg. 583).
Accordingly, the claimed invention was anticipated by the teachings of Postle.
Claim Rejections - 35 USC § 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 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.
First rejection
Claim 2-3 rejected under 35 U.S.C. 103 as being unpatentable over Postle as applied to claim 1, 7, and 10 above, and further in view of Renna et al (Regulation of the Bacillus subtilis alsS, alsD, and alsR genes involved in post-exponential-phase production of acetoin. J Bacteriol. 1993 Jun;175(12):3863-75) and Mueller (US20130330809A1).
As discussed above, the claims were anticipated in view of the teachings of Postle.
The reference does not explicitly teach using an alsS or alsD gene.
However, Renna teaches a nucleic acid construct including the alsR and alsSD gene (a first and second gene as in claim 1) used for production of acetoin in recombinant E. coli JM2r and JM109 microorganisms that also contains a promoter upstream the genes (see abstract, throughout; see Table 1; pg. 3863 and Fig. 1). Renna also teaches that the alsS and alsD gene is from a single operon, and alsS condenses 2 molecules of pyruvate to form acetolactate and alsD spontaneously decarboxylates the acetolactate to form acetoin (i.e., a gene encodes and enzyme that synthesizes acetoin from pyruvate as in claim 2; alsS and alsD as in claim 3; see pg.3863, col 1, paragraph 2).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the construct of Postle and include the alsS/D genes as taught by Renna 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 Renna explicitly teaches that the alsS and alsD gene successfully condenses 2 molecules of pyruvate to form acetolactate and decarboxylates the acetolactate to form acetoin.
Neither reference teaches the second gene encodes an enzyme that synthesizes 2,3-butanediol from acetoin.
However, Mueller teaches “recombinant microorganisms adapted to express or overexpress key enzymes in the MEK and/or 2-butanol biosynthesis pathways. Such microorganisms, such as the carboxydotrophic acetogen Clostridium autoethanogenum, can ferment substrates comprising CO. The overall scheme involves the production of 2-butanol from (R,S)-2,3-butanediol and the conversion of (R)-acetoin to (S)-2,3-butanediol” (see abstract). Mueller teaches creation of recombinant microorganisms containing nucleic acids that encode an enzyme that catalyzes conversion of (R)-Acetoin to (R,S)-2,3-butanediol; comprising sequences that encode 2,3-butanediol dehydrogenase (see paragraphs 31-35).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the nucleic acid construct of Postle and Renna and include the nucleic acid sequence that encodes 2,3-butanediol dehydrogenase as taught by Mueller to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modifications because Mueller explicitly teaches nucleic acid sequences capable of successfully encode 2,3-butanediol dehydrogenase that is useful for conversion of (R)-acetoin to (S)-2,3-butanediol in a recombinant microorganism.
Accordingly, the claimed invention was prima facie obvious at the time of filing, especially in the absence of evidence to the contrary.
Second rejection
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Postle, Renna, and Mueller as applied to claim 2-3 above, and further in view of Dischert (US 9506093 B2).
As discussed above, the claims were rendered prima facie obvious in view of the teachings of Postle, Renna and Mueller.
None of the references explicitly teach the rho-independent terminator of the nucleic acid construct is selected from SEQ ID NO: 5-8.
However, Dischert (in a similar field of endeavor) teaches recombinant microorganisms such as E. coli (see abstract, claim 1-9) for production of fermentation metabolic products like methionine (see abstract). Dischert teaches construction of plasmids for use in E. coli MG1655 that includes a terminator (see SEQ ID NO 16) with 100% sequence identity to instant SEQ ID NO 5 (see alignment below):
PNG
media_image1.png
709
785
media_image1.png
Greyscale
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the nucleic acid construct of Postle, Renna and Mueller and include the sequence of rho-independent terminator as taught by Dischert to arrive at the claimed invention. One of ordinary skill would have been motivated to make the modification because Dischert teaches a rho-independent terminator that can be useful to produce fermentation products in recombinant E. coli.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Bremond et al (WO 2016012561 A1): teaches recombinant yeast microorganisms for production of acetoin.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
Prosecution Insights