DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are still at issue and are present for examination.
Election/Restrictions
Applicant's election without traverse of the invention of Group 1, claims 1-17, to a modified Type 1 O-methyltransferase, in the paper of 7/9/2026, is acknowledged. Applicant's election without traverse of the invention the following species:
Species Group 1: Phe337 of Sorghum bicolor stilbene;
Species Group 2: Ile144 of SbSOMT;
Species Group 3: Sorghum bicolor SbSOMT;
Species Group 4: SEQ ID NO:1; and
Species Group 5: 0-methylated stilbenoid.
in the paper of 7/9/2026, is acknowledged.
Claims 13, 15 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Applicants filing of information disclosure statements on 5/21/2024, 5/24/2024, 9/12/2024, 3/5/2026 and 11/6/2024 are acknowledged and have been considered.
Claim Objections
Claims 8-12 are objected to because of the following informalities:
Claims 8-12 recite a number of SEQ ID NOs, some of which are out of numerical order. It is suggested that the SEQ ID Nos be listed in numerical order.
Claims 10-11 depend from rejected claim 1.
Appropriate correction and/or comment is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8, 12, 14, 16 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Claims 1-8, 12, 14, 16 and 17 are directed to a modified 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and additionally wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., 106 USPQ2d 1972 (June 13, 2013). Uniprot Accession No. A0A199W2N8, Oct 2016, which discloses a naturally occurring 1 O-methyltransferase (OMT), from pineapple (Ananas comosus) wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid, evidence that a 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid is a naturally occurring enzyme and is thus not patent eligible.
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.
Claims 1-12, 14, 16 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 (claims 3-11 and 16 dependent from) 2, 12, 14 are indefinite in the reference to an amino acid corresponding to Phe337 and Ile144 absent a reference amino acid sequence (i.e. SEQ ID NO). In the interest of advancing prosecution the amino acids corresponding to Phe337 and Ile144 are interpreted using instant SEQ ID NO:1 as a reference sequence.
Appropriate correction and/or comment is required.
Claim Rejections - 35 USC § 112
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(s) 1-9, 12, 14, 16 and 17 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.
Claim(s) 1-9, 12, 14, 16 and 17 are directed to all possible modified Type 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid. The specification, however, only provides the representative species of that Type 1 O-methyltransferase comprising the amino acid sequence of SEQ ID NO: 1, wherein the amino acid corresponding to Phe337 of SEQ ID NO:1 is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SEQ ID NO:1 is substituted with a polar amino acid, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in the disclosed species. The specification also fails to describe additional representative species of these modified OMTs by any identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim(s) 1-9, 12, 14, 16 and 17 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for that Type 1 O-methyltransferase comprising the amino acid sequence of SEQ ID NO: 1, wherein the amino acid corresponding to Phe337 of SEQ ID NO:1 is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SEQ ID NO:1 is substituted with a polar amino acid, does not reasonably provide enablement for all possible modified Type 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid. The specification, however, only provides the representative species of that Type 1 O-methyltransferase comprising the amino acid sequence of SEQ ID NO: 1, wherein the amino acid corresponding to Phe337 of SEQ ID NO:1 is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SEQ ID NO:1 is substituted with a polar amino acid. 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 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (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 claim(s).
Claim(s) 1-9, 12, 14, 16 and 17 are so broad as to encompass all possible modified Type 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid. The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of modified Type 1 O-methyltransferases encompassed by the claims. The claims rejected under this section of U.S.C. 112, first paragraph, place minimal structural limits on the modified Type 1 O-methyltransferases encompassed by the claims. Since the amino acid sequence of a protein 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. However, in this case the disclosure is limited to that Type 1 O-methyltransferase comprising the amino acid sequence of SEQ ID NO: 1, wherein the amino acid corresponding to Phe337 of SEQ ID NO:1 is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SEQ ID NO:1 is substituted with a polar amino acid.
While recombinant and mutagenesis techniques are known, it is not routine in the art to screen for multiple substitutions or multiple modifications, as encompassed by the instant claims, and the positions within a 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.
The specification does not support the broad scope of the claims which encompass any possible modified Type 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid., because the specification does not establish: (A) regions of the Type 1 O-methyltransferases which may be modified effecting the esterase activity; (B) the general tolerance of Type 1 O-methyltransferases to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue of an Type 1 O-methyltransferase with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. Because of this lack of guidance, the extended experimentation that would be required to determine which substitutions would be acceptable to retain the required Type 1 O-methyltransferase and the fact that the relationship between the sequence of a peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable (e.g., see Ngo et al. in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz et al. (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495; Franceus et al., J. Ind. Microbiol. Biotechnol. Vol 44, pp 687-695, 2017), it would require undue experimentation for one skilled in the art to arrive at the majority of those modified Type 1 O-methyltransferase of the claimed genus.
Thus, applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including any modified Type 1 O-methyltransferase (OMT), wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid. 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 those modified Type 1 O-methyltransferases having the desired biological characteristics is 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-8, 12, 14 and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Uniprot Accession No. A0A199W2N8, Oct 2016.
Uniprot Accession No. A0A199W2N8, Oct 2016, discloses a naturally occurring 1 O-methyltransferase (OMT), from pineapple (Ananas comosus) wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid. While it is recognized that the amino acid sequence of the O-methyltransferase (OMT), from pineapple (Ananas comosus) has only 46% sequence identity to instant SEQ ID NO:1, it still anticipates the claims because the only structural requirements of the claims are a Phe337 substitution with an asparagine residue and a Ile144 substitution with an asparagine residue. It is further noted that the taught O-methyltransferase (OMT), from pineapple (Ananas comosus) wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid comprises additional modifications which would alter the production of O-methylated stilbenoid.
Thus, claim(s) 1-8, 12, 14 and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Uniprot Accession No. A0A199W2N8, Oct 2016.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-8, 12, 14, 16 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bearson et al. (U.S. Patent No. 7,732,666) and Uniprot Accession No. A0A199W2N8, Oct 2016.
Bearson et al. (U.S. Patent No. 7,732,666) disclose the cloning and expression of an O-methyltransferase gene cloned from sorghum, the sorghum O-methyltransferase-3 gene, SbOMT3. Bearson et al. disclose that quantitative real-time RT-PCR and recombinant enzyme studies with putative O-methyltransferase sequences obtained from an EST data set from sorghum led to the identification of the novel root hair-specific O-methyltransferase designated SbOMT3. Bearson et al. teach that transgenic plants which express SbOMT3 can convert resveratrol into pterostilbene in planta. SbOMT3 is also involved in the biosynthesis of sorgoleone.
Uniprot Accession No. A0A199W2N8, Oct 2016, discloses a naturally occurring 1 O-methyltransferase (OMT), from pineapple (Ananas comosus) wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid. While it is recognized that the amino acid sequence of the O-methyltransferase (OMT), from pineapple (Ananas comosus) has only 46% sequence identity to instant SEQ ID NO:1, it still anticipates the claims because the only structural requirements of the claims are a Phe337 substitution with an asparagine residue and a Ile144 substitution with an asparagine residue. It is further noted that the taught O-methyltransferase (OMT), from pineapple (Ananas comosus) wherein the amino acid corresponding to Phe337 of Sorghum bicolor stilbene OMT (SbSOMT) is substituted with a polar amino acid and wherein the amino acid corresponding to Ile144 of SbSOMT is substituted with a polar amino acid comprises additional modifications which would alter the production of O-methylated stilbenoid.
One of skill in the art before the effective filing date of the claimed invention would have been motivated to express the O-methyltransferase (OMT), from pineapple (Ananas comosus) as taught by Uniprot Accession No. A0A199W2N8, Oct 2016, and isolate the O-methyltransferase (OMT), from pineapple (Ananas comosus) and measure its activity relative to the O-methyltransferases n a solution as taught by Bearson et al. using the expression techniques and activity assays taught by Bearson et al. The expectation of success is high based upon the high level of skill in the art of recombinant protein expression as exemplified by Bearson et al. who teach all of the methods necessary to express and analyze the expressed O-methyltransferase (OMT), from pineapple (Ananas comosus).
Thus, claim(s) 1-8, 12, 14, 16 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bearson et al. (U.S. Patent No. 7,732,666) and Uniprot Accession No. A0A199W2N8, Oct 2016.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
8/5/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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