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
This application is a continuation of PCT/US2022/078805.
The amendment filed on July 6, 2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 6-9) with a species election of (1) E.coli as the host cell and (2) acetyl-CoA acetyltransferase (AtoB), hydroxymethylglutaryI-CoA synthase (HMGS), hydroxymethylglutaryI-CoA reductase (HMGR), alcohol acyltransferase (ATF), mevalonate kinase (MK), and mevalonate diphosphate decarboxylase (PMD) in the reply filed on January 14, 2025 is acknowledged.
Status of Claims
Claims 6-9 are pending.
Claims 6-9 are under examination.
Claim for Domestic Priority
Applicants' claim for domestic priority under 35 USC 119(e) to US provisional application 63/341,670 filed on 05/13/2022 and 63/272,593 filed on10/27/2021 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 26, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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.
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.
Claim 7 is 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 7 recites the phrase "acetylation of isoprenol and acetyl-CoA to generate isoprenyl acetate". The metes and bounds of the phrase in the context of the claim are not clear. ATF1 does not acetylate acetyl-CoA. Instead, ATF1 transfers the acetyl group of acetyl-CoA to isoprenol to generate isoprenyl acetate. Appropriate correction is required.
Claim 9 is 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 9 recites the phrase "amino acid residues indicated by an asterisk and/or period show in Figure 5". The metes and bounds of the phrase in the context of the claims are not clear. Claims are to be complete in themselves. Incorporation by reference to a specific figure or table is permitted only in exceptional circumstances. See MPEP 2173.05(s). Appropriate correction is required.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 6-9 are 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.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' In this case, the claims have been broadly interpreted to encompass (A) any genetically modified host cells comprising (B) any heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and any promiscuous phosphatase to generate isoprenol and (C) (i) any alcohol acyltransferase (ATF1), any homologous enzyme thereof, and any variants thereof having one or more conservative amino acid substitutions, and (ii) any ATF1 having at least 70% sequence identity to SEQ ID NO:3-6 and any variant thereof, wherein the ATF1 acetylates isoprenol to isoprenyl acetate. Therefore, the claims are drawn to (A) a genus of genetically modified host cells comprising (B) genus of heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and promiscuous phosphatase to generate isoprenol having unknown structure but having the function of generating isoprenol and (C) genus of ATF1 having unknown structure but having the function of acetylating isoprenol to isoprenyl acetate.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. 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…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The recitations of “heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and promiscuous phosphatase” and “ATF1” fails to provide a sufficient description of the genus of enzymes as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus.
A genetically modified E. coli comprising an IPP-bypass MVA pathways for C5 alcohol production by utilizing promiscuous activities of phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA) was known in the art, see Kang (Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. Metab Eng. 2019 Dec;56:85-96. Epub 2019 Sep 6. – form PTO-892) and Kang (Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production. Metab Eng. 2016 Mar;34:25-35. Epub 2015 Dec 17- form PTO-892). S. cerevisiae ATF1 having the function of acetylating isoprenol to isoprenyl acetate was also known in the art, see Lee (US 9,200,298 – form PTO-892). However, neither the prior art nor the instant specification provides guidance on any genetically modified host cell comprising any IPP-bypass MVA pathways comprising any promiscuous phosphomevalonate decarboxylase and phosphatase and any ATF1, wherein the host cell produces isoprenyl acetate from isoprenol.
The specification is limited to description of a genetically modified E. coli comprising an IPP-bypass MVA pathway for C5 alcohol production by utilizing promiscuous activities of phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA) and S. cerevisiae ATF1, wherein said E. coli produces isoprenyl acetate via isoprenol. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or 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.” In view of the widely variant species encompassed by the genus, the example described above is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus.
Further, one of skill in the art could identify polypeptides having at least 70% sequence identity to SEQ ID NO:3, 4, 5, or 6 and variants of ATF1. However, there is no teaching regarding which 30% of the amino acids can vary from SEQ ID NO:3, 4, 5, or 6 or which amino acids can vary from any ATF1 and result in polypeptide having the function of acetylating isoprenol to isoprenyl acetate. An important consideration is that structure is not necessarily a reliable indicator of function. In the instant case, there is no disclosure relating similarity of structure to conservation of function. Conservation of structure is not necessarily a surrogate for conservation of function. Since the claimed invention is that of an enzyme, and there is no disclosure of the domains responsible for galactose oxidase activity, the absence of information may be persuasive that those of skill in the art would not take the disclosure as generic.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the inventions of claims 6-9.
Claims 6-9 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 genetically modified E. coli comprising an IPP-bypass MVA pathway for C5 alcohol production by utilizing promiscuous activities of phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA) and S. cerevisiae ATF1, wherein said E. coli produces isoprenyl acetate via isoprenol, does not reasonably provide enablement for (A) any genetically modified host cells comprising (B) any heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and promiscuous phosphatase to generate isoprenol having unknown structure but having the function of generating isoprenol and (C) any ATF1 having unknown structure but having the function of acetylating isoprenol to isoprenyl acetate. 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 use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The breadth of the claims.
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' In this case, the claims have been broadly interpreted to encompass (A) any genetically modified host cells comprising (B) any heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and any promiscuous phosphatase to generate isoprenol and (C) (i) any alcohol acyltransferase (ATF1), any homologous enzyme thereof, and any variants thereof having one or more conservative amino acid substitutions, and (ii) any ATF1 having at least 70% sequence identity to SEQ ID NO:3-6 and any variant thereof, wherein the ATF1 acetylates isoprenol to isoprenyl acetate. Therefore, the claims are drawn to (A) any genetically modified host cells comprising (B) any heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and promiscuous phosphatase to generate isoprenol having unknown structure but having the function of generating isoprenol and (C) any ATF1 having unknown structure but having the function of acetylating isoprenol to isoprenyl acetate.
The claims are not commensurate with the enablement provided by the disclosure with regard to the extremely large number of genetically modified cells. In the instant case, the specification is limited to a genetically modified E. coli comprising an IPP-bypass MVA pathway for C5 alcohol production by utilizing promiscuous activities of phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA) and S. cerevisiae ATF1, wherein said E. coli produces isoprenyl acetate via isoprenol.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification.
While enzyme isolation techniques, recombinant and mutagenesis techniques were known in the art at the time of the invention, e.g. mutagenesis, and it is routine in the art to screen for variants comprising multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within the protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
In the absence of: (a) a rational and predictable scheme for making any genetically modified host cells comprising any heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and any promiscuous phosphatase to generate isoprenol and (b) a rational and predictable scheme for making any polypeptide having at least 70% sequence identity to any one of SEQ ID NO:3-6 any variants thereof, wherein the polypeptide has the function of acetylating isoprenol to isoprenyl acetate the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, as is the case herein, the specification must provide a reasonable amount of guidance which respect to the direction in which the experimentation should proceed so that a reasonable number of species can be selected for testing. In view of the fact that such guidance has not been provided in the instant specification, it would require undue experimentation to enable the full scope of the claims.
The state of prior art, the relative skill of those in the art, and predictability or unpredictability of the art.
Since the amino acid sequence of the mutant determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. In the instant case, neither the specification or the art provide a correlation between structure and activity such that one of skill in the art can envision the structure of any heterologous IPP-bypass MVA pathways utilizing promiscuous activities of any phosphomevalonate decarboxylase and any phosphatase to generate isoprenol or any polypeptides having the function of acetylating isoprenol to isoprenyl acetate or predict said function of a polypeptide from its primary structure. In addition, the art does not provide any teaching or guidance as to (1) which amino acids within the polypeptide of any one of SEQ ID NO:3-6 or any functional fragment thereof that can be modified and which ones are conserved such that one of skill in the art can make the recited polypeptides having the function of acetylating isoprenol to isoprenyl acetate, (2) which segments of SEQ ID NO:3-6 that are essential for polypeptides having the function of acetylating isoprenol to isoprenyl acetate, and (3) the general tolerance of the polypeptide of SEQ ID NO:3-6 to structural modifications and the extent of such tolerance. The art clearly teaches that changes in a protein's amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are required for that activity is highly unpredictable. At the time of the invention there was a high level of unpredictability associated with altering a polypeptide sequence with an expectation that the polypeptide will maintain the desired activity. For example, Studer (Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes. Biochem. J. (2013) 449, 581–594. – form PTO-892) teach that (1) protein engineers are frequently surprised by the range of effects caused by single mutations that they hoped would change only one specific and simple property in enzymes, (2) the often surprising results obtained by experiments where single mutations are made reveal how little is known about the rules of protein stability, and (3) the difficulties in designing de novo stable proteins with specific functions.
A genetically modified E. coli comprising an IPP-bypass MVA pathways for C5 alcohol production by utilizing promiscuous activities of phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA) was known in the art, see Kang (Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. Metab Eng. 2019 Dec;56:85-96. Epub 2019 Sep 6. – form PTO-892) and Kang (Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production. Metab Eng. 2016 Mar;34:25-35. Epub 2015 Dec 17- form PTO-892). S. cerevisiae ATF1 having the function of acetylating isoprenol to isoprenyl acetate was also known in the art, see Lee (US 9,200,298 – form PTO-892). However, neither the prior art nor the instant specification provides guidance on any genetically modified host cell comprising any IPP-bypass MVA pathways comprising any promiscuous phosphomevalonate decarboxylase and phosphatase and any ATF1, wherein the host cell produces isoprenyl acetate from isoprenol.
Fransceus (J Ind Microbiol Biotechnol. 2017 May;44(4-5):687-695. – form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – form PTO-892) discloses challenges in the prediction of protein stability in the occurrence of multiple mutations. “Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects”.
The amount of direction or guidance presented and the existence of working examples.
The specification is limited to a genetically modified E. coli comprising an IPP-bypass MVA pathway for C5 alcohol production by utilizing promiscuous activities of phosphomevalonate decarboxylase (PMD) and an E. coli-endogenous phosphatase (AphA) and S. cerevisiae ATF1, wherein said E. coli produces isoprenyl acetate via isoprenol. However, the speciation fails to provide any information as to (1) structural elements required in an IPP-bypass MVA pathway that produces isoprenol or (2) structural elements required in a polypeptide having the function of acetylating isoprenol to isoprenyl acetate.
Thus, in view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability of the prior art in regard to structural changes and their effect on function and the lack of knowledge about a correlation between structure and function, an undue experimentation would be necessary one having ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of polypeptides having the desired biological characteristics recited in the claims are unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
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.
Claim(s) 6 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kang A (Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. Metab Eng. 2019 Dec;56:85-96. Epub 2019 Sep 6. – form PTO-892).
Regarding claim 6, Kang discloses a genetically modified E. coli host cell comprising a heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and a promiscuous phosphatase to generate isoprenol (abstract and page 85, 2nd paragraph through page 86, 2st paragraph, Figure 1, and page 86, Section 2.2). The IPP bypass comprises a promiscuous phosphatase, as evidence by Kang B (abstract. Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production. Metab Eng. 2016 Mar;34:25-35. Epub 2015 Dec 17- form PTO-892). The heterologous mevalonate pathway of Kang A comprises acetyl-CoA acetyltransferase (AtoB), hydroxymethylglutaryI-CoA synthase (HMGS), hydroxymethylglutaryI-CoA reductase (HMGR), mevalonate kinase (MK), and mevalonate diphosphate decarboxylase (PMD) (Fig. 1).
Therefore, the reference of Kang A anticipates claim 6.
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.
Claim(s) 6-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kang A (Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. Metab Eng. 2019 Dec;56:85-96. Epub 2019 Sep 6. – form PTO-892) and Lee (US 9,200,298 – form PTO-892), as evidence by Kang B (Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production. Metab Eng. 2016 Mar;34:25-35. Epub 2015 Dec 17- form PTO-892), P40353 (UniProtKB/Swiss-Prot Database. June 17, 2020 – form PTO-892), and Fuji (US 5,728,412 – form PTO-892).
Regarding claim 6, Kang discloses a genetically modified E. coli host cell comprising a heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and a promiscuous phosphatase to generate isoprenol (abstract and page 85, 2nd paragraph through page 86, 1st paragraph, Figure 1, and page 86, Section 2.2). The IPP bypass comprises a promiscuous phosphatase, as evidenced by Kang B (abstract). The heterologous mevalonate pathway of Kang A of comprises acetyl-CoA acetyltransferase (AtoB), hydroxymethylglutaryI-CoA synthase (HMGS), hydroxymethylglutaryI-CoA reductase (HMGR), mevalonate kinase (MK), and mevalonate diphosphate decarboxylase (PMD) (Fig. 1).
Kang does not disclose expressing an alcohol acyltransferase having at least 70% sequence identity to SEQ ID NO:3 of the instant application or variants thereof to catalyze acetylation of the isoprenol by transferring the acetyl group from acetyl-CoA to generate isoprenyl acetate.
Regarding claims 7-8, Lee discloses a genetically modified E. coli host cell comprising S. cerevisiae alcohol acetyltransferase, such as the S. cerevisiae alcohol acetyltransferase having Accession No. P40353 (ATF1) or the S. cerevisiae alcohol acetyltransferase (AAT1, synonymous with ATF1) disclosed in U.S. Patent Nos 5,728,412, to acetylate isoprenol and acetyl-CoA to generate isoprenyl acetate (Column 6, line 46 through Column 8, line 42, Table 1, and claim 1). The S. cerevisiae alcohol acetyltransferase having Accession No. P40353 and the S. cerevisiae alcohol acetyltransferase disclosed in U.S. Patent Nos 5,728,412 have at least 70% sequence identity to SEQ ID NO:3 of the instant application (see the sequence alignments below). Lee discloses that the hydrogenated isoprenyl acetates are fuel targets (Column 6, lines 46-52).
Regarding claim 9, MPEP 2113 states that the “patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed ATF1 variant implied is the same whether the variant is obtained from SEQ ID NO:3 or is obtained from any source (including wild type proteins), as long as the resulting product has the structural limitations recited in the claims (does not have one or more conservative amino acids indicated by an asterisk and/or period shown Figure 5). The S. cerevisiae alcohol acetyltransferase ATF1 disclosed in U.S. Patent Nos 5,728,412 does not have an K reside at the position corresponding to 183 of SEQ ID NO:3 and said position is marked with an asterisk in Figure 5 (see the sequence alignment below).
Therefore, in combining the teachings of the above references, it would have been obvious to one having ordinary skill in the art before the claimed invention was effectively filed to modify the genetically modified E. coli host cell of Kang A to express S. cerevisiae alcohol acetyltransferase (ATF1). One having ordinary skill in the art would have been motivated to do so in order to acetylate isoprenol to generate isoprenyl acetate, which is a fuel target. One having ordinary skill in the art would have had a reasonable expectation of success since Kang A discloses a genetically modified E.coli host cell comprising a heterologous mevalonate pathway with an IPP bypass and a promiscuous phosphate to generate isoprenol and Lee teaches a genetically modified E.coli host cell expressing S. cerevisiae alcohol acetyltransferase (ATF1) which acetylates isoprenol to isoprenyl acetate.
Therefore, the above references render claims 6-9 prima facie obvious.
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 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 9,200,298 (reference patent) in view of Kang A (Optimization of the IPP-bypass mevalonate pathway and fed-batch fermentation for the production of isoprenol in Escherichia coli. Metab Eng. 2019 Dec;56:85-96. Epub 2019 Sep 6. – form PTO-892) and Lee (US 2010/0180491 – form PTO-1449), as evidence by Kang B (Isopentenyl diphosphate (IPP)-bypass mevalonate pathways for isopentenol production. Metab Eng. 2016 Mar;34:25-35. Epub 2015 Dec 17- form PTO-892), P40353 (UniProtKB/Swiss-Prot Database. June 17, 2020 – form PTO-892), and Fuji (US 5,728,412 – form PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the reference patent are directed to a genetically modified host cell producing isoprenyl acetate.
Regarding claim 6-7 of the instant application, claims 1, 7, and 23 of the reference patent recites a genetically modified E. coli host cell comprising a S. cerevisiae alcohol acetyltransferase (AAT) that catalyzes esterification of isoprenol to produce isoprenyl acetate.
The claims of the reference patent do not recite a genetically modified E. coli comprising a heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and a promiscuous phosphatase to generate isoprenol nor S. cerevisiae alcohol acetyltransferase (AAT) having at least 70% sequence identity to SEQ ID NO:3 of the instant application and variants thereof.
Regarding claim 6, Kang discloses a genetically modified E. coli comprising a heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and a promiscuous phosphatase to generate increased production of isoprenol (abstract and page 85, 2nd paragraph through page 86, 1st paragraph, Figure 1, and page 86, Section 2.2). The IPP bypass comprises a promiscuous phosphatase, as evidenced by Kang B (abstract). The heterologous mevalonate pathway of Kang A comprises acetyl-CoA acetyltransferase (AtoB), hydroxymethylglutaryI-CoA synthase (HMGS), hydroxymethylglutaryI-CoA reductase (HMGR), mevalonate kinase (MK), and mevalonate diphosphate decarboxylase (PMD) (Fig. 1).
Regarding claims 7-8, Lee discloses a genetically modified E. coli host cell comprising S. cerevisiae alcohol acetyltransferase, such as the S. cerevisiae alcohol acetyltransferase having Accession No. P40353 (ATF1) or the S. cerevisiae alcohol acetyltransferase (AAT1, synonymous with ATF1) disclosed in U.S. Patent Nos 5,728,412, to acetylate isoprenol and acetyl-CoA to generate isoprenyl acetate ([0037]-[0043] Table 1, and claim 1). The S. cerevisiae alcohol acetyltransferase having Accession No. P40353 and the S. cerevisiae alcohol acetyltransferase disclosed in U.S. Patent Nos 5,728,412 have at least 70% sequence identity to SEQ ID NO:3 of the instant application (see the sequence alignments below). Lee discloses that the hydrogenation of isoprenyl acetates are fuel targets (Column 6, lines 46-52).
Regarding claim 9, MPEP 2113 states that the “patentability of a product does not depend on its method of production.”. In the instant case, the structure of the claimed ATF1 variant implied is the same whether the variant is obtained from SEQ ID NO:3 or is obtained from any source, as long as the resulting product has the structural limitations recited in the claims (does not have one or more conservative amino acids indicated by an asterisk and/or period shown Figure 5). The S. cerevisiae alcohol acetyltransferase disclosed in U.S. Patent Nos 5,728,412 does not have a Lys reside at the position corresponding to 183 of SEQ ID NO:3 and said position is marked with an asterisk in Figure 5 (see the sequence alignment below).
Therefore, it would have been obvious to one having ordinary skill in the art to modify the claims of the reference patent by introducing a heterologous mevalonate pathway with the isopentenyl diphosphate (IPP) bypass and a promiscuous phosphatase. One having ordinary skill in the art would have been motivated to do so in order to produce isoprenol, the precursor to isoprenyl acetate. One having ordinary skill in the art would have had a reasonable expectation of success since the reference patent recites a genetically modified E. coli comprising a S. cerevisiae alcohol acetyltransferase that acetylates isoprenol to isoprenyl acetate, Kang teaches a genetically modified E.coli comprising a heterologous mevalonate pathway with an IPP bypass and a promiscuous phosphate to generate isoprenol, and Lee teaches a genetically modified E.coli expressing S. cerevisiae alcohol acetyltransferase (ATF1) which acetylates isoprenol to isoprenyl acetate.
Therefore, the conflicting claims are not patentably distinct from each other.
Conclusion
Claims 6-9 are pending.
Claims 6-9 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YONG D PAK whose telephone number is (571)272-0935. The examiner can normally be reached M-Th: 5:30 am - 3:30 pm.
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/YONG D PAK/Primary Examiner, Art Unit 1652
Sequence alignment between the Saccharomyces cerevisiae ATF1 of SEQ ID NO:3 of the instant application (“Qy”) and the Saccharomyces cerevisiae AAT1 of Lee (“Db”)
ATF1_YEAST
ID ATF1_YEAST Reviewed; 525 AA.
AC P40353; D6W370; Q08901;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 10-JUN-2026, entry version 170.
DE RecName: Full=Alcohol O-acetyltransferase 1 {ECO:0000303|PubMed:8085822};
DE Short=AATase 1 {ECO:0000303|PubMed:8085822};
DE EC=2.3.1.84 {ECO:0000269|PubMed:28160314, ECO:0000269|PubMed:7764365};
DE EC=3.1.2.20 {ECO:0000269|PubMed:28160314};
GN Name=ATF1 {ECO:0000303|PubMed:8085822}; OrderedLocusNames=YOR377W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Kyokai No.7;
RX PubMed=8085822; DOI=10.1128/aem.60.8.2786-2792.1994;
RA Fujii T., Nagasawa N., Iwamatsu A., Bogaki T., Tamai Y., Hamachi M.;
RT "Molecular cloning, sequence analysis, and expression of the yeast alcohol
RT acetyltransferase gene.";
RL Appl. Environ. Microbiol. 60:2786-2792(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874; DOI=10.1038/387s098;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=7764365; DOI=10.1271/bbb.57.2094;
RA Minetoki T., Bogaki T., Iwamatsu A., Fujii T., Hamachi M.;
RT "The purification, properties and internal peptide sequences of alcohol
RT acetyltransferase isolated from Saccharomyces cerevisiae Kyokai No. 7.";
RL Biosci. Biotechnol. Biochem. 57:2094-2098(1993).
RN [5]
RP INDUCTION.
RX PubMed=9055409; DOI=10.1128/aem.63.3.910-915.1997;
RA Fujii T., Kobayashi O., Yoshimoto H., Furukawa S., Tamai Y.;
RT "Effect of aeration and unsaturated fatty acids on expression of the
RT Saccharomyces cerevisiae alcohol acetyltransferase gene.";
RL Appl. Environ. Microbiol. 63:910-915(1997).
RN [6]
RP FUNCTION.
RX PubMed=9758847; DOI=10.1128/aem.64.10.4076-4078.1998;
RA Fukuda K., Yamamoto N., Kiyokawa Y., Yanagiuchi T., Wakai Y., Kitamoto K.,
RA Inoue Y., Kimura A.;
RT "Balance of activities of alcohol acetyltransferase and esterase in
RT Saccharomyces cerevisiae is important for production of isoamyl acetate.";
RL Appl. Environ. Microbiol. 64:4076-4078(1998).
RN [7]
RP INDUCTION.
RX PubMed=9675816;
RX DOI=10.1002/(sici)1097-0061(19980615)14:8<711::aid-yea263>3.0.co;2-8;
RA Fujiwara D., Yoshimoto H., Sone H., Harashima S., Tamai Y.;
RT "Transcriptional co-regulation of Saccharomyces cerevisiae alcohol
RT acetyltransferase gene, ATF1 and delta-9 fatty acid desaturase gene, OLE1
RT by unsaturated fatty acids.";
RL Yeast 14:711-721(1998).
RN [8]
RP INDUCTION.
RX PubMed=10487921;
RX DOI=10.1002/(sici)1097-0061(19990915)15:12<1183::aid-yea444>3.0.co;2-j;
RA Fujiwara D., Kobayashi O., Yoshimoto H., Harashima S., Tamai Y.;
RT "Molecular mechanism of the multiple regulation of the Saccharomyces
RT cerevisiae ATF1 gene encoding alcohol acetyltransferase.";
RL Yeast 15:1183-1197(1999).
RN [9]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=10653746; DOI=10.1128/aem.66.2.744-753.2000;
RA Lilly M., Lambrechts M.G., Pretorius I.S.;
RT "Effect of increased yeast alcohol acetyltransferase activity on flavor
RT profiles of wine and distillates.";
RL Appl. Environ. Microbiol. 66:744-753(2000).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12957907; DOI=10.1128/aem.69.9.5228-5237.2003;
RA Verstrepen K.J., Van Laere S.D., Vanderhaegen B.M., Derdelinckx G.,
RA Dufour J.P., Pretorius I.S., Winderickx J., Thevelein J.M., Delvaux F.R.;
RT "Expression levels of the yeast alcohol acetyltransferase genes ATF1, Lg-
RT ATF1, and ATF2 control the formation of a broad range of volatile esters.";
RL Appl. Environ. Microbiol. 69:5228-5237(2003).
RN [11]
RP INDUCTION.
RX PubMed=14654433; DOI=10.1016/s1567-1356(03)00166-1;
RA Verstrepen K.J., Derdelinckx G., Dufour J.P., Winderickx J.,
RA Pretorius I.S., Thevelein J.M., Delvaux F.R.;
RT "The Saccharomyces cerevisiae alcohol acetyl transferase gene ATF1 is a
RT target of the cAMP/PKA and FGM nutrient-signalling pathways.";
RL FEMS Yeast Res. 4:285-296(2003).
RN [12]
RP FUNCTION.
RX PubMed=12937998; DOI=10.1007/s10295-003-0070-0;
RA Horton C.E., Huang K.X., Bennett G.N., Rudolph F.B.;
RT "Heterologous expression of the Saccharomyces cerevisiae alcohol
RT acetyltransferase genes in Clostridium acetobutylicum and Escherichia coli
RT for the production of isoamyl acetate.";
RL J. Ind. Microbiol. Biotechnol. 30:427-432(2003).
RN [13]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=15042596; DOI=10.1002/yea.1100;
RA Verstrepen K.J., Van Laere S.D., Vercammen J., Derdelinckx G., Dufour J.P.,
RA Pretorius I.S., Winderickx J., Thevelein J.M., Delvaux F.R.;
RT "The Saccharomyces cerevisiae alcohol acetyl transferase Atf1p is localized
RT in lipid particles.";
RL Yeast 21:367-377(2004).
RN [15]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=16845703; DOI=10.1002/yea.1382;
RA Lilly M., Bauer F.F., Lambrechts M.G., Swiegers J.H., Cozzolino D.,
RA Pretorius I.S.;
RT "The effect of increased yeast alcohol acetyltransferase and esterase
RT activity on the flavour profiles of wine and distillates.";
RL Yeast 23:641-659(2006).
RN [16]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=18597084; DOI=10.1007/s00253-008-1573-4;
RA Etschmann M.M., Koetter P., Hauf J., Bluemke W., Entian K.D., Schrader J.;
RT "Production of the aroma chemicals 3-(methylthio)-1-propanol and 3-
RT (methylthio)-propylacetate with yeasts.";
RL Appl. Microbiol. Biotechnol. 80:579-587(2008).
RN [17]
RP FUNCTION.
RX PubMed=17891501; DOI=10.1007/s00449-007-0159-3;
RA Singh R., Vadlani P.V., Harrison M.L., Bennett G.N., San K.Y.;
RT "Aerobic production of isoamyl acetate by overexpression of the yeast
RT alcohol acetyl-transferases AFT1 and AFT2 in Escherichia coli and using
RT low-cost fermentation ingredients.";
RL Bioprocess Biosyst. Eng. 31:299-306(2008).
RN [18]
RP FUNCTION.
RX PubMed=25310977; DOI=10.1016/j.celrep.2014.09.009;
RA Christiaens J.F., Franco L.M., Cools T.L., De Meester L., Michiels J.,
RA Wenseleers T., Hassan B.A., Yaksi E., Verstrepen K.J.;
RT "The fungal aroma gene ATF1 promotes dispersal of yeast cells through
RT insect vectors.";
RL Cell Rep. 9:425-432(2014).
RN [19]
RP FUNCTION, AND BIOTECHNOLOGY.
RX PubMed=25306884; DOI=10.1007/s10295-014-1522-4;
RA Dong J., Xu H., Zhao L., Chen Y., Zhang C., Guo X., Hou X., Chen D.,
RA Zhang C., Xiao D.;
RT "Enhanced acetate ester production of Chinese liquor yeast by
RT overexpressing ATF1 through precise and seamless insertion of PGK1
RT promoter.";
RL J. Ind. Microbiol. Biotechnol. 41:1823-1828(2014).
RN [20]
RP BIOTECHNOLOGY.
RX PubMed=25281839; DOI=10.1016/j.ymben.2014.09.006;
RA Layton D.S., Trinh C.T.;
RT "Engineering modular ester fermentative pathways in Escherichia coli.";
RL Metab. Eng. 26:77-88(2014).
RN [21]
RP BIOTECHNOLOGY.
RX PubMed=24609358; DOI=10.1038/nchembio.1476;
RA Rodriguez G.M., Tashiro Y., Atsumi S.;
RT "Expanding ester biosynthesis in Escherichia coli.";
RL Nat. Chem. Biol. 10:259-265(2014).
RN [22]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=25093817; DOI=10.1371/journal.pone.0104141;
RA Lin J.L., Wheeldon I.;
RT "Dual N- and C-terminal helices are required for endoplasmic reticulum and
RT lipid droplet association of alcohol acetyltransferases in Saccharomyces
RT cerevisiae.";
RL PLoS ONE 9:E104141-E104141(2014).
Query Match 95.4%; Score 2691; Length 525;
Best Local Similarity 97.1%;
Matches 498; Conservative 7; Mismatches 8; Indels 0; Gaps 0;
Qy 1 MNEIDGKSQGPVQQECLKEMIQNRHARCMGSVEDLYVALNREHLYRNFCTYGELSDYCSR 60
||||| |:| ||||||||||||| ||| |||||||||||||::|||||||||||||||:|
Db 1 MNEIDEKNQAPVQQECLKEMIQNGHARRMGSVEDLYVALNRQNLYRNFCTYGELSDYCTR 60
Qy 61 DQLTLALREICLKNPTLLHIVLPTRWPNHENYYRSSEYYSRPHPVHDYISVLQELKLSGV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DQLTLALREICLKNPTLLHIVLPTRWPNHENYYRSSEYYSRPHPVHDYISVLQELKLSGV 120
Qy 121 VLNEQPEYSAVMKQILEEFKNSEGSYNAGVFKLSTTLTIPYFGPTGPSWRLICLPEEHTE 180
||||||||||||||||||||||:||| | :|||:||||||||||||||||||||||||||
Db 121 VLNEQPEYSAVMKQILEEFKNSKGSYTAKIFKLTTTLTIPYFGPTGPSWRLICLPEEHTE 180
Qy 181 KWKKFIFVSNHCMSDGRSSIHFFHDLRDELNNIKTPPKKLDYIFKYEEDYQLLRKLPEPI 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KWKKFIFVSNHCMSDGRSSIHFFHDLRDELNNIKTPPKKLDYIFKYEEDYQLLRKLPEPI 240
Qy 241 EKVIDFRPPYLFIPKSLLSGFIYNHLRFSSKGVCMRMDDVEKTDDVVTEIINISPTEFQA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EKVIDFRPPYLFIPKSLLSGFIYNHLRFSSKGVCMRMDDVEKTDDVVTEIINISPTEFQA 300
Qy 301 IKANIKSNIQGKCTITPFLKGCWFVSLHKWGKFFKPLNFEWLTDIFIPADCRSQLPDDDE 360
||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||
Db 301 IKANIKSNIQGKCTITPFLHVCWFVSLHKWGKFFKPLNFEWLTDIFIPADCRSQLPDDDE 360
Qy 361 MRQMYRYGANVGFIDFTPWISEFDMNDNKENFWPLIEHYHEVISEALRNKKHLHGLGFNI 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MRQMYRYGANVGFIDFTPWISEFDMNDNKENFWPLIEHYHEVISEALRNKKHLHGLGFNI 420
Qy 421 QGFVQKYVNIDKVMCDRAIGKRRGGTLLSNVGLFNQLEEPDAKYSICDLAFGQFQGSWHQ 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 QGFVQKYVNIDKVMCDRAIGKRRGGTLLSNVGLFNQLEEPDAKYSICDLAFGQFQGSWHQ 480
Qy 481 AFSLGVCSTNVKGMNIVVASTKNVVGSQESLEE 513
|||||||||||||||||||||||||||||||||
Db 481 AFSLGVCSTNVKGMNIVVASTKNVVGSQESLEE 513
Sequence alignment between the Saccharomyces cerevisiae ATF1 of SEQ ID NO:3 of the instant application (“Qy”) and the alcohol acetyltransferase of 5,728,412 (“Db”)
US-08-465-334-17
Filing date in PALM: 1995-06-05
Sequence 17, US/08465334
Patent No. 5728412
GENERAL INFORMATION
APPLICANT: FUJII, Toshio
APPLICANT: IWAMATSU, Akihiro
APPLICANT: YOSHIMOTO, Hiroyuki
APPLICANT: MINETOKI, Toshitaka
APPLICANT: BOGAKI, Takayuki
APPLICANT: NAGASAWA, Naoshi
TITLE OF INVENTION: ALCOHOL ACETYLTRANSFERASE GENES AND USE
TITLE OF INVENTION: THEREOF
CURRENT APPLICATION NUMBER: US/08/465,334
CURRENT FILING DATE: 05-JUN-1995
PRIOR APPLICATION NUMBER: US 08/077,939
PRIOR FILING DATE: 18-JUN-1993
PRIOR APPLICATION NUMBER: JP 62997/1993
PRIOR FILING DATE: 26-FEB-1993
PRIOR APPLICATION NUMBER: JP 184328/1992
PRIOR FILING DATE: 18-JUN-1992
NUMBER OF SEQ ID NOS: 19
SEQ ID NO 17
LENGTH: 525
TYPE: PRT
Query Match 95.3%; Score 2688; Length 525;
Best Local Similarity 96.9%;
Matches 497; Conservative 8; Mismatches 8; Indels 0; Gaps 0;
Qy 1 MNEIDGKSQGPVQQECLKEMIQNRHARCMGSVEDLYVALNREHLYRNFCTYGELSDYCSR 60
||||| |:| ||||||||||||| ||| |||||||||||||::|||||||||||||||:|
Db 1 MNEIDEKNQAPVQQECLKEMIQNGHARRMGSVEDLYVALNRQNLYRNFCTYGELSDYCTR 60
Qy 61 DQLTLALREICLKNPTLLHIVLPTRWPNHENYYRSSEYYSRPHPVHDYISVLQELKLSGV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DQLTLALREICLKNPTLLHIVLPTRWPNHENYYRSSEYYSRPHPVHDYISVLQELKLSGV 120
Qy 121 VLNEQPEYSAVMKQILEEFKNSEGSYNAGVFKLSTTLTIPYFGPTGPSWRLICLPEEHTE 180
||||||||||||||||||||||:||| | :|||:||||||||||||||||||||||||||
Db 121 VLNEQPEYSAVMKQILEEFKNSKGSYTAKIFKLTTTLTIPYFGPTGPSWRLICLPEEHTE 180
Qy 181 KWKKFIFVSNHCMSDGRSSIHFFHDLRDELNNIKTPPKKLDYIFKYEEDYQLLRKLPEPI 240
||:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KWRKFIFVSNHCMSDGRSSIHFFHDLRDELNNIKTPPKKLDYIFKYEEDYQLLRKLPEPI 240
Qy 241 EKVIDFRPPYLFIPKSLLSGFIYNHLRFSSKGVCMRMDDVEKTDDVVTEIINISPTEFQA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EKVIDFRPPYLFIPKSLLSGFIYNHLRFSSKGVCMRMDDVEKTDDVVTEIINISPTEFQA 300
Qy 301 IKANIKSNIQGKCTITPFLKGCWFVSLHKWGKFFKPLNFEWLTDIFIPADCRSQLPDDDE 360
||||||||||||||||||| |||||||||||||||||||||||||||||||||||||||
Db 301 IKANIKSNIQGKCTITPFLHVCWFVSLHKWGKFFKPLNFEWLTDIFIPADCRSQLPDDDE 360
Qy 361 MRQMYRYGANVGFIDFTPWISEFDMNDNKENFWPLIEHYHEVISEALRNKKHLHGLGFNI 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MRQMYRYGANVGFIDFTPWISEFDMNDNKENFWPLIEHYHEVISEALRNKKHLHGLGFNI 420
Qy 421 QGFVQKYVNIDKVMCDRAIGKRRGGTLLSNVGLFNQLEEPDAKYSICDLAFGQFQGSWHQ 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 QGFVQKYVNIDKVMCDRAIGKRRGGTLLSNVGLFNQLEEPDAKYSICDLAFGQFQGSWHQ 480
Qy 481 AFSLGVCSTNVKGMNIVVASTKNVVGSQESLEE 513
|||||||||||||||||||||||||||||||||
Db 481 AFSLGVCSTNVKGMNIVVASTKNVVGSQESLEE 513
Prosecution Insights