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 .
The Response of 27 April 2026 has been entered.
Claims 1, 2, 7, 9 and 11-15 are currently pending.
Election/Restrictions
Applicant's election with traverse of the species of: ferulic acid ester as component (a), tyramine as component (b), variant I208A_L209F_N288A as the enzyme variant and CHES as the buffer in the reply filed on 27 April 2026 is acknowledged. The traversal is on the ground(s) that the invention as claimed can be searched without undue burden due to structural similarities among the claimed compounds/enzymes. This is not found persuasive because each compound/variant comprises a distinct compound/enzyme and thus gives rise to different searches. Moreover, the issue is deemed moot since the claims have been found free of the prior art (see below).
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 7, 9 and 11-15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites that component (a) is "at least one of a methyl, an ethyl or a vinyl ester of ferulic, caffeic or coumaric acid" and that component (b) is "at least one amine selected from tyramine, octopamine or dopamine". The above recitations are improper Markush groups in that the groups are open-ended (i.e. using "or" rather than "and") (see MPEP 2173.05(h) - A Markush grouping is a closed group of alternatives).
Claim 1 further recites the phrase "preferably" in step (vii), which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 9 recites "wherein component (c)" followed by a list of enzyme variants. The claims lacks language indicating how the list limits the claim. The rejection can be overcome by amending to recite "wherein component (c) is a P. calidifontis VA1 esterase variant selected from the group consisting of:" along with an "and" between the penultimate and last variants in the list.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites that "component (a) is esters of ferulic acid" (i.e. any ester), whereas claim 1 (from which claim 2 depends) limits component (a) to "at least one of a methyl, an ethyl or a vinyl ester of ferulic, caffeic or coumaric acid". Claim 2 is thus broader than claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Allowable Subject Matter
Claims 1, 2, 7, 9 and 11-15 are free of the prior art and would be allowable upon resolution of the above 112(b) rejections. The closest prior art is represented by:
i) Müller et al., ACS Catalysis 11.24 (2021): 14906-14915. Muller is a review article about "promiscuous" acyltransferases capable of catalyzing acyltransferase reactions in water. Muller teaches that the key limitation for aqueous acyltransferase reactions is the balance between acyl transfer and hydrolysis (AT/H ratio) (p. 14909, 1st ¶; p. 14911-14912, under CURRENT CHALLENGES AND PROTEIN ENGINEERING). Muller teaches that the AT/H of any particular reaction depends on the nature of the acyl donor and the acceptor as well as enzyme-specific factors such as active-site hydrophobicity (p. 14911-14912, under CURRENT CHALLENGES AND PROTEIN ENGINEERING). Muller teaches that while active-site hydrophobicity analysis can be used to predict acyltransferase activity of some substrates, but this approach is not suitable for polar acceptors (such as tyramine, octopamine, dopamine in the instant claims) (p. 14912, 2nd ¶ under SUMMARY AND OUTLOOK).
iii) Terholsen et al., ChemBioChem 23.13 (2022): e202200254 (cited in IDS of 25 March 2024). Terholsen teaches the use of the I208A_L209F_N288A variant of PestE to catalyze the conversion of hydroxytyrosol (acceptor) and ethyl acetate (donor) to form 3-hydroxytyrosol acetate (Abstract). The reaction of Terholsen takes place at acidic pH and uses a biphasic reaction system wherein an organic phase is used to extract the product and prevent subsequent hydrolysis (p. 1, 1st ¶; p. 2, 2nd ¶ and Scheme 1). Terholsen does not teach or suggest the donors, acceptors or reaction conditions of the instant claims. In view of Muller's teachings regarding the dependence of promiscuous acyltransferase activity on the nature of the donor and acceptor and the unpredictability of polar acceptors, the claimed reaction would not have been a predictable extension of the teachings of Terholsen.
ii) Zeng et al., Journal of Biotechnology 334 (2021): 51-57 (cited in IDS of 25 March 2024). Zeng teaches reaction of a tyramine acceptor with ferulic, caffeic and coumaric acids to produce hydroxycinnamic acids (Fig. 2), but uses an enzyme (Candida antarctica lipase B) distinct from PestE in a nonaqueous solvent (MTBE) (p. 52, under 2.2. General procedure).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657