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
Pursuant to a preliminary amendment filed on August 15, 2025, claims 1 – 3, 5, 7 – 10, 13, 16 – 17, 19, 21, 23 – 29 are currently pending in the instant application. (Claims 4, 6, 11 – 12, 14 – 15, 18, 20, 22, and 30 were previously canceled). Claims 1, 23 and 28 are independent claims.
Therefore, claims 1 – 3, 5, 7 – 10, 13, 16 – 17, 19, 21, 23 – 29 are under examination to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 15, 2024, October 3, 2024, October 4, 2024, June 17, 2025, and February 26, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed August 15, 2024, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/SG2023/050106, filed February 22, 2023, which claims the benefit of SG10202201742V, filed February 22, 2022. Certified translated copies of the SG10202201742V, were filed on 8/15/2024.
Therefore, the earliest priority date is February 22, 2022.
Claim Rejection - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 – 3, 5, 7 – 10, 13, 16 – 17, 19, 21, 23 – 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite for the recitation of “one or more vectors comprising a polynucleotide sequence encoding” in lines 1 – 2. It is unclear whether all sequences encoded by the polynucleotide are the same, and whether the vectors comprise the same polynucleotide sequences. Thus, the metes and bounds of the claim cannot be determined. It is unclear how many of the pathway genes are being encoded by the polynucleotide.
Claim 2 is indefinite for the recitation of “the mevalonate pathway genes are encoded by one or more polynucleotide sequences on one or more vectors” in lines 2 - 3. It is unclear if a single gene is encoded by a polynucleotide sequence is on vector or is split across multiple vectors.
Claim 3,5,8,10,13,17,19,21, 23 are indefinite for the recitation of ….optionally” such as recited in claim 2, line 4. It is unclear exactly what are limitations of the claim. For example, in claim 3, it is unclear whether the hmgR gene should be truncated, or whether a non-truncated hmgR reads on the instantly recited claims. Thus, the metes and bounds of the claim cannot be determined.
For the purpose of compact prosecution, the claims have been interpreted as not comprising the optional limitations.
Claim 3 is indefinite because a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. In the present instance, claim 3 recites the broad recitation “the more than one diphosphate synthase gene, prenyl transferase gene or combinations thereof” in line 3; and claim also recite “is a geranyl pyrophosphate synthase (GPPS) or a farnesyl pyrophosphate synthase (FPPS) gene” in lines 3, which is the narrower statement of the range/limitation, Accordingly, the metes and bounds of the claim are not clear. Claims 9-10 are indefinite insofar as they depend on claim 3
Claim 9 is indefinite for the recitation of “GPPS or FPPS gene is isolated from a prokaryote, a eukaryote, a plant, or combinations thereof” in lines 2 – 3. It is unclear how the GPPS or FPPS gene can be isolated from a combination of prokaryotes and eukaryotes for use in the host cell.
Claim 9 is indefinite for the recitation of “GPPS or FPPS gene is isolated from a prokaryote, a eukaryote, a plant, or combinations thereof” in lines 2 – 3.
Claim 16 is indefinite insofar as it ultimately depends from claim 1.
Claims 24 – 27 are indefinite insofar as they ultimately depend on claim 23.
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 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 – 3, 5, 7, 9, 10, 21, and 23 – 24, are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as
being anticipated by Zhang et al. (hereinafter referred to as “Zhang”) (Zhang, C.. et al. Bioinformatics-aided identification, characterization and applications of mushroom linalool synthases. Commun Biol 4, 223 (2021)).
Regarding claims 1 – 3, Zhang teaches the expression of AAE3_109435 in a GPP accumulating E. coli that co-expressed the native enzymes DXS, IDI, and ispA_S80F mutant (GPPS) (pg. 2, right column, last paragraph) (GPPS is a prenyltransferase gene of the linalool pathway, idi is a mevalonate pathway gene, and AAE3_109435 is a linalool synthase gene). Zhang teaches that the pET-11a vector was modified with ispA_S80F (GPP synthase) or ispA (FPP synthase) from E. coli, and that the strain also that a plasmid that overexpresses the enzymes DXS and IDI (pg. 10, left column, first paragraph) (interpreted as the mevalonate pathway genes and linalool pathway genes are encoded by one or more polynucleotide sequences on one or more vectors).
Regarding claim 5 and 7, Zhang teaches that the linalool synthase is from Agrocybe pediades (pg. 2, right column, second paragraph).
Regarding claims 9, 10, and 21, Zhang teaches that the ispA_S80F (GPP synthase) or ispA (FPP synthase) from E. coli (pg. 10, left column, first paragraph).
Regarding claim 23 and 24, Zhang teaches the expression and purification of linalool synthases, wherein the E.coli cells were induced with 0.1mM IPTG, and re-suspended in glycerol (pg. 9, left column, fifth paragraph).
Claim Rejection - 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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1 and 8, are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al., as
applied to claim 1, supra, and further in view of Croteau et al. (US 20050204417 A1, published September 15, 2005).
The teachings of claim 1 are supra.
Zhang does not teach the ApLS is truncated at the C-terminal (claim 8).
Regarding claim 8, Croteau teaches geranyl diphosphate synthase proteins (GPPS) specifically Seq ID No: 10 (Paragraph [0015]) (Seq ID No: 10 has a 100% alignment score with instantly claimed Seq ID No: 11). Croteau teaches that Seq ID No: 10 is expressed in an E.coli construct (Paragraph [0074]).
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A person of ordinary skill in the art would have had a reasonable expectation of success in substituting gpps of Agrocybe pediades, as taught by Zhang, for the gpps of Seq ID No; 10, as taught by Croteau because both are explicitly taught as being used in E. coli strains. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Claims 1, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al.,
as applied to claim 1, supra, and further in view of Lin et al. (hereinafter referred to as “Lin”) (Lin PC. Et al. Enhanced limonene production in a fast-growing cyanobacterium through combinatorial metabolic engineering. Metab Eng Commun. 2021 Jan 26;12:e00164. doi: 10.1016/j.mec.2021.e00164. PMID: 33659180; PMCID: PMC7890178.).
Zhang does not teach the GPPS is isolated from Abies grandis (AgGPPS) (claim 13).
Regarding claim 13, Lin teaches the expressing and modulating the expression level of a specific GPP synthase(GPPS) from Abies grandis (pg. 2, left column, second paragraph). Lin teaches that the gpps gene was codon optimized for expression in E. coli (pg. 2, right column, second paragraph).
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting gpps of Agrocybe pediades, as taught by Zhang, for the gpps from Abies grandis, as taught by Lin, because both are explicitly taught as being used in E. coli strains. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Claim 1 and 17, are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al., as
applied to claim 1, supra, and further in view of Zhou et al. (hereinafter referred to as “Zhou) (Zhou J. et al. Geranyl diphosphate synthase: an important regulation point in balancing a recombinant monoterpene pathway in Escherichia coli. Enzyme Microb Technol. 2015 Jan;68:50-5. doi: 10.1016/j.enzmictec.2014.10.005. Epub 2014 Oct 25. PMID: 25435505.).
The teachings of claim 1 are supra.
Zhang does not teach the GPPS is titrated by RBS engineering (claim 17).
Regarding claim 17, Zhou teaches that the expression of GPPS was optimized by using ribosomal binding sites (RBSs) designed to have different translation initiation rates (TIRs) (Abstract). Zhou teaches the recombinant geraniol-producing strains were significantly affected by different expression levels of GPPS which could be modulated by using synthetic RBSs, such that the optimized expression of GPPS in the recombinant strains enabled cells to achieve good cell growth, stable plasmid maintenance, and high geraniol production (pg. 55, left column, first paragraph).
Therefore, in view of high geraniol production as taught by Zhou, it would have been prima facia obvious for one of ordinary skill in the art to optimize the GPPS as taught by Zhang, using RBS engineering, as taught by Zhou, with a reasonable expectation of success in enhancing the recombinant host cell growth, and enhancing the stability of the plasmid in the host cell. It would have been prima facia obvious to combine the cited references because Zhang teaches the of a GPPS, and Zhou teaches the optimization of a GPPS using RBS to achieve good cell growth and stable plasmid maintenance.
Claims 1, 16, 19, 28, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over
Zhang et al., as applied to claim 1, supra, and further in view of as being anticipated by Protzko (US 20210108238 A1, published April 15, 2021).
The teachings of claim 1 are supra.
Zhang does not teach the a t7 RNA polymerase promoter (claim 16), the host cell is deficient in one gene involved in amino acid degradation (claim 19), and a kit for producing linalool (claims 28 and 29).
Regarding claims 16, 19, and 28, Protzko teaches the use of E.coli strain MG1655 with lambda DE3 (a phage construct that expresses T7 RNA polymerase under the control of a lacUV5 promoter) that was used as a host strain and propagated at 37° C (Paragraph [0123]). Protzko teaches that in this strain tryptophan deaminase (tnaA) knocked out (Paragraph [0127]).
Regarding claim 29, Protzko teaches that the cells are resuspended in M9 media (Paragraph [0129]).
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting E.coli strain, as taught by Zhang, for the E.coli strain MG1655 with lambda DE3 wherein tnaA has been knocked out, as taught by Protzko, because both strains are explicitly taught as host cells. Therefore, these compositions are functional equivalents in the art, and substituting one for the other would have been obvious at the time of the invention. “When a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious.” See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) at 1395-1396, quoting Sakraida v. AG Pro, Inc., 425 U.S. 273 (1976) and In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious”).
Claim 1 and 25 - 27 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et
al., as applied to claim 1, supra.
The teachings of claim 1 are supra.
Regarding claims 25 – 27, Zhang does not specifically teach the titers of linalool production (claim 25), the concentration of linalool per OD600, and the carbon yield of linalool production. However, per M.P.E.P. § 2144/05(11), differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCP A 1955). Since the instant specification is not appear to support the notion that quantitative yields of claims 25 – 27 are not considered to support patentability.
Conclusion
Claims 1 – 3, 5, 7 – 10, 13, 16 – 17, 19, 21, 23 – 29 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/ Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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