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 371 of PCT/EP2021/086644.
The response filed on October 10, 2025 has been entered.
Election/Restrictions
Applicant's election with traverse of Group XII (claim 25, method of using the acyl transferase of SEQ ID NO:2 and variants/fragments thereof) with a species election of an acyl transferase having at least 60% sequence identity to SEQ ID NO:2 in the reply filed on October 10, 2025 is acknowledged. The traversal is on the ground(s) that the number of Groups indicated is seemingly excessive and the prior art does not disclose or suggest using an alcohol acyl transferase for esterifying linalool to linalyl acetate. This is not found persuasive because the number of Groups are based on the number of inventions. There is no maximum number of groups or that the number of Groups cannot exceed the number of claims. The traversal is also on the ground(s) that the prior art does not disclose or suggest using an alcohol acyl transferase for esterifying linalool to linalyl acetate. This is not found persuasive. The technical feature linking the Groups are directed to various alcohol acyl transferases capable of esterifying a tertiary monoterpene alcohol since not all claims recite an alcohol acyl transferase having the property of esterifying linalool to linalyl acetate. Further, Wiese (Die Biosynthese von acetylierten Monoterpenen in Thymian (Thymus vulgaris). Dissertation. June 23, 2020 – form 1449) discloses an alcohol acyl transferase TvAAT3 having linalool acyl transferase activity, wherein the amino acid sequence of TvAAT3 comprises a fragment of SEQ ID NO:2 of the instant application and/or comprises at least two contiguous amino acids of SEQ ID NO:2 of the instant application (abstract, page 44, Figure 3.11 at page 55, and Section 3.4.5 at page 57 and see the sequence alignment below).
The requirement is still deemed proper and is therefore made FINAL.
Claim 25 is partially directed to non-elected inventions. For examination purposes, examination of claim 25 is limited to the elected invention, a method of preparing linalyl acetate using the alcohol acyl transferase of SEQ ID NO:2 and variants/fragments thereof.
Status of Claims
Claims 16-30 are pending.
Claims 1-24 and 26-30 are withdrawn.
Claim 25 is under examination.
Foreign Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 3, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, for example pages 6, 13-16, 33, 51, 55, and 64. 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.
Drawings
The Drawings are objected to because the consensus sequence in Figure 5 contains amino acid sequences but is not identified by a sequence identifier. When a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used, either in the drawing or in the Brief Description of the Drawings.
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 25 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 25 recites the limitations “Table 1” and “Table 2” in clause (iv). The metes and bounds of the limitation in the context of the claim 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).
Claim 25 recites the limitation “any of those amino acids.. for those positions” in clause (iv). The metes and bounds of the limitation in the context of the claim are not clear. It is unclear what amino acids are modified. Clarification is requested.
Regarding claim 25, the phrase "such that" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim 25 is 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 the instant case, the limitation “an amino acid sequence as shown in.. SEQ ID NO:2” has been interpreted as any two contiguous amino acids of SEQ ID NO:2. Therefore, the claim has been broadly interpreted as a method of preparing linalyl acetate comprising esterifying linalool to linalyl acetate in the presence of an alcohol acyl transferase having (a) any amino acid sequence comprising as little as any two contiguous aminos of SEQ ID NO:2, (b) any amino acid sequence with at least 60% sequence identity to SEQ ID NO:2, (c) any fragment of the amino acid sequence of (a) or (b), (d) the alcohol dehydrogenase of (a), (b), or (c), wherein the amino acid sequence does not have a Tryptophan at the positions corresponding to 371 and 372 of SEQ ID NO:2, or (e) the alcohol acyl transferase of (a), (b), or (c) further comprising one or more amino acid modifications disclosed in Tables 1 or 2, wherein the alcohol acyl transferase of (a)-(e) is capable of esterifying linalool to linalyl acetate, is capable of esterifying linalool wherein at least 30% by mass of the linalool is esterified, and is capable of esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. Therefore, the claim is drawn to a method of preparing linalyl acetate comprising esterifying linalool to linalyl acetate in the presence of a genus of alcohol acyl transferase having unknown structure but having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting.
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 “linalool acyl transferase activity”, “capable of esterifying linalool to linalyl acetate”, “esterifying linalool such that at least 30% by mass of the linalool is esterified” and “esterifying linalool such that at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting” fail to provide a sufficient description of the genus of the enzymes used in the claimed method 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.
The claimed method requires an alcohol acyl transferase having the function of esterifying linalool to linalyl acetate. Although some alcohol acyl transferases were known in the art, alcohol acyl transferases were knownto have either no or very low activity in using tertiary alcohols, such as linalool, see Zaks (Biosynthesis of linalyl acetate and other terpenes in lemon mint (Mentha aquatica var. citrata, Lamiaceae) glandular trichomes. Israel Journal of Plant Sciences, 56(3), 233–244 page 234. 2008 – form PTO-892, 2nd full paragraph and page 242, 1st paragraph). Similarly, polypeptides having at least 60% sequence identity to SEQ ID NO:2 or variants/fragments thereof having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting were not known in the art. A search of SEQ ID NO:2 is limited to hypothetical polypeptides as shown below.
PNG
media_image1.png
995
1187
media_image1.png
Greyscale
The specification is limited to a method of producing linalyl acetate comprising esterifying linalool to linalyl acetate in the presences of an alcohol acyl transferase having the amino acid sequence of SEQ ID NO:2. 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 examples 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 genus of alcohol acyl transferase used in the claimed method.
Further, one of skill in the art could identify variants and fragments of SEQ ID NO:2 or polypeptides having 60% sequence identity with SEQ ID NO:2. However, there is no teaching regarding which amino acids of SEQ ID NO:2 can vary and result in a polypeptide having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting.
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”.
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.
While general knowledge in the art may have allowed one of skill in the art to identify other polypeptides expected to have the same or similar tertiary structure, there was no general knowledge in the art in the ability of the claimed genus of polypeptides having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. Accordingly, one of skill in the art would not accept the disclosure of the alcohol acyl transferase of SEQ ID NO:2 as representative species of the genus of alcohol acyl transferases used in the claimed method.
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 claim 25.
Claim 25 is 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 method of producing linalyl acetate comprising esterifying linalool to linalyl acetate in the presences of an alcohol acyl transferase having the amino acid sequence of SEQ ID NO:2, does not reasonably provide enablement for a method of preparing linalyl acetate comprising esterifying linalool to linalyl acetate in the presence of any alcohol acyl transferase having unknown structure but having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. 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 the instant case, the limitation “an amino acid sequence as shown in.. SEQ ID NO:2” has been interpreted as any two contiguous amino acids of SEQ ID NO:2. Therefore, the claim has been broadly interpreted as a method of preparing linalyl acetate comprising esterifying linalool to linalyl acetate in the presence of an alcohol acyl transferase having (a) any amino acid sequence comprising as little as any two contiguous aminos of SEQ ID NO:2, (b) any amino acid sequence with at least 60% sequence identity to SEQ ID NO:2, (c) any fragment of the amino acid sequence of (a) or (b), (d) the alcohol dehydrogenase of (a), (b), or (c), wherein the amino acid sequence does not have a Tryptophan at the positions corresponding to 371 and 372 of SEQ ID NO:2, or (e) the alcohol acyl transferase of (a), (b), or (c) further comprising one or more amino acid modifications disclosed in Tables 1 or 2, wherein the alcohol acyl transferase of (a)-(e) is capable of esterifying linalool to linalyl acetate, is capable of esterifying linalool wherein at least 30% by mass of the linalool is esterified, and is capable of esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. Therefore, the claim is drawn to a method of preparing linalyl acetate comprising esterifying linalool to linalyl acetate in the presence of any alcohol acyl transferase having unknown structure but having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting.
The claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polypeptides having unknown structure but having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. The specification is limited to a method of producing linalyl acetate comprising esterifying linalool to linalyl acetate in the presences of an alcohol acyl transferase having the amino acid sequence of SEQ ID NO:2.
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) rational and predictable scheme for esterifying linalool to linalyl acetate using polypeptides having at least 60% sequence identity or fragments and variants thereof and (b) a correlation between structure and having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting, the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. One of skill in the art would have to test these infinite possible polypeptides to determine which polypeptides have the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. 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.
The claimed method requires an alcohol acyl transferase having the function of esterifying linalool to linalyl acetate. Although some alcohol acyl transferases were known in the art, alcohol acyl transferases were not known to have either no or very low activity in using tertiary alcohols, such as linalool, see Zaks (Biosynthesis of linalyl acetate and other terpenes in lemon mint (Mentha aquatica var. citrata, Lamiaceae) glandular trichomes. Israel Journal of Plant Sciences, 56(3), 233–244 page 234. 2008 – form PTO-892, 2nd full paragraph and page 242, 1st paragraph). Similarly, polypeptides having at least 60% sequence identity to SEQ ID NO:2 or variants/fragments thereof having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting were not known in the art. A search of SEQ ID NO:2 is limited to hypothetical polypeptides as shown below.
PNG
media_image1.png
995
1187
media_image1.png
Greyscale
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 polypeptides having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting 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 SEQ ID NO:2 that can be modified and which ones are conserved such that one of skill in the art can make and use the polypeptide to produce linalyl acetate, (2) which segments of the polypeptide of SEQ ID NO:2 are essential for having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting, and (3) the general tolerance of the polypeptide of SEQ ID NO:2 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.
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 method of producing linalyl acetate comprising esterifying linalool to linalyl acetate in the presences of an alcohol acyl transferase having the amino acid sequence of SEQ ID NO:2. However, the speciation fails to provide any information as to the structural elements required in a polypeptide having the function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting. No correlation between structure and function of esterifying linalool to linalyl acetate, esterifying linalool wherein at least 30% by mass of the linalool is esterified, and esterifying linalool wherein at least 50 µg of monoterpene ester per minute and per gram of alcohol acyl transferase is produced at 30°C at a pH in the range of 6.05 to 8.5 under conditions wherein the substrate are not limiting has been presented.
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 (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.
Claim(s) 25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticpated by Wiese (Die Biosynthese von acetylierten Monoterpenen in Thymian (Thymus vulgaris). Dissertation. June 23, 2020 – form 1449).
MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' In the instant case, the limitation “an amino acid sequence as shown in.. SEQ ID NO:2” has been interpreted as any two contiguous amino acids of SEQ ID NO:2.
Regarding claim 25, Wiese discloses a method of preparing linalyl acetate comprising esterifying linalool to linalyl acetate in the presence of an alcohol acyl transferase, TvAAT3 (abstract, Figure 3.11 at page 55, and Section 3.4.5 at page 57). The amino acid sequence of TvAAT3 of Wiese comprises a fragment of SEQ ID NO:2 of the instant application or comprises at least two contiguous amino acids of SEQ ID NO:2 of the instant application (see page 44 and the sequence alignment below).
Therefore, the reference of Wiese anticipates claim 25.
Relevant Art
Zaks (Biosynthesis of linalyl acetate and other terpenes in lemon mint (Mentha aquatica var. citrata, Lamiaceae) glandular trichomes. Israel Journal of Plant Sciences, 56(3), 233–244 page 234. 2008 – form PTO-892) discloses an enzyme extract from lemon lint having linalool acyl transferase activity but does not disclose the amino acid sequence of the linalool acyl transferase (page 235, “Enzyme extraction” and “Alcohol acetyl transferase”).
Conclusion
Claims 16-30 are pending.
Claims 16-24 and 26-30 are withdrawn.
Claim 25 is 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.
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, Robert Mondesi can be reached on 408-918-7584. 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.
/YONG D PAK/Primary Examiner, Art Unit 1652
The sequence alignment between the alcohol acyl transferase of SEQ ID NO:2 of the instant application (“Qy”) and the alcohol acyl transferase TvAAT3 of Wiese (“Db”)
Title: US-18-267-491A-2
Perfect score: 2235
Sequence: 1 MKIDVETISREMIKPSTPTP..........EKEVMAKFENDQELLAYVST 426
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 419 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : AASEQ2_01082026_093503.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 714.5 32.0 419 1 AASEQ2_01082026_093503
ALIGNMENTS
RESULT 1
AASEQ2_01082026_093503
Query Match 32.0%; Score 714.5; DB 1; Length 419;
Best Local Similarity 37.0%;
Matches 159; Conservative 73; Mismatches 165; Indels 33; Gaps 12;
Qy 6 ETISREMIKPSTPTPNHLRHYQFSHLDQIGPPFYISLLYFYHLDDDKLVSNNRHLFSDSL 65
: |: :::|||||||: |:|: | :||: | || |::|| | || | |
Db 3 QIIASQIVKPSTPTPSSTRNYKLSSIDQVAPSIYIPLIFFYESDQSKL----HEQISRCL 58
Qy 66 KSSLSNVLTKYYPLAGRI-KNNYVDCNDEGVFFSEAKVSCQLSEIINEPEFPSEFKKLLP 124
| ||| | :||||| | :|::||||| || |||:| :| : : | : |:|||
Db 59 KKSLSEALAIFYPLAGEIEENSFVDCNDGGVELSEARVHARLLQFLKNPNLEEDLKQLLP 118
Qy 125 FDQEKDVVSFDSLAIA IQVNMFNCGNVAVAVMISHKIADGSSLSTFTKNWAAAARGE-SE 183
| :: : :: : |:|| :|| | |||: || | : | |||| ||| |:
Db 119 --AEASSYRDNAFQLKVKTSYFDCGGIAVGVCFSHKVGDGGSAAAFVNAWAAACRGEVSK 176
Qy 184 NVFPEFVAARLFPP-EDAGGGSGTSFDPRPKKVVLKKFLFEGSKITALRDKYGFDNRIYP 242
| | | ||| | :| || :: ::|:|:| |: |: |
Db 177 ITCPAFDLALRFPPRETLSSAAGFGLDPVEDEIATERFVFDGKKMEKLKRAASNGEVKNP 236
Qy 243 TRVEALSAFLW-SRLAASNRIKVSSERPCML--IHAVNLRKRVEPQLPADSFGNLFAFAV 299
:||| :|||:| | : |:|: :: | |||||| | | | :||| |
Db 237 SRVEVVSAFIWRSFIEAANKRNQTAPPPASFTAAHAVNLRPRAVPSFPDQTFGNCVTVAY 296
Qy 300 TVLDENDDDG----MVNKFRDAISKIDKDYLKAKKVEHSELIDLGITNGEKFGG--GELG 353
: :||| :|:| | || :| :|: |: |: :|: || |
Db 297 AKISSEEDDGGMSVLVSKLRAAIRGVDGEYV--NKIVKDEI------SGDAAGGEMSAAG 348
Qy 354 YCIISSLCKFPVYEADFGLGKPTWVAWGCFPYKNVIHFIDAKSGDGIEVWVHLEKE---- 409
|: || :||||: ||| ||| ||| | | : |: :||| ||:| ::
Db 349 NCVFSSWWRFPVYDVDFGWGKPVWVATATMPVINTVVFMATPCREGIEAWVNLSRDNDDS 408
Qy 410 ---VMAKFEN 416
: ||: |
Db 409 FETLRAKYTN 418