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 office action is a response to applicant’s communication submitted August 27, 2026, wherein the rejections of record in the previous action are maintained. This application is a national stage application of PCT/US20221/018134, filed February 15, 2021, which claims benefit of provisional applications 63/001165, filed March 27, 2020, and 62/976672, filed February 14, 2020.
Claims 1, 11-18, and 25-32 are pending in this application.
Claims 12-18, 25, and 26 are withdrawn from consideration.
Claims 1, 11, and 27-32 as amended are examined on the merits herein.
The following rejections of record in the previous action are maintained:
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.
Claims 1, 11, 27, 28, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Suga et al. (US pre-grant publication 2011/0275119, of record in previous action) in view of Cabrele et al. (NPL Reference 2 included with 9/5/2024 PTO-1449)
Suga et al. discloses a method of synthesizing a polypeptide comprising using an ARS ribozyme to acylate tRNA with an amino acid, including nonnatural amino acids such as beta-amino acids, gamma- amino acids, and delta- amino acids, among various other amino acids. (p. 2 paragraph 22, p. 4 paragraph 72, also figure 3)
Suga et al. does not disclose an aminoacyl tRNA wherein the amino acid is a cyclic amino acid as recited in claim 1 as amended. However, Cabrele et al. discloses construction of peptides containing beta amino acid building blocks. (p. 9718 left column first paragraph) Specific beta amino acids discussed as being incorporated into peptides include cyclic amino acids falling within claims 1, 11, 27, 28, and 31 as amended. (p. 9719 figure 1B)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the method of Suga et al. to make acylated tRNAs bearing any of the beta-amino acids described by Cabrele et al. One of ordinary skill in the art would have seen the disclosure of Cabrele et al. as suggesting that producing peptides containing these amino acids is useful, and would have seen the disclosure of Suga et al. as demonstrating generally that a variety of beta-amino acids could be attached to tRNAs in order to be incorporated into peptides.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1, 11, 27, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Suga et al. (US pre-grant publication 2011/0275119, of record in previous action) in view of Torres et al. (Reference of record in previous action)
Suga et al. discloses a method of synthesizing a polypeptide comprising using an ARS ribozyme to acylate tRNA with an amino acid, including nonnatural amino acids such as beta-amino acids, gamma- amino acids, and delta- amino acids, among various other amino acids. (p. 2 paragraph 22, p. 4 paragraph 72, also figure 3)
Suga et al. does not disclose an aminoacyl tRNA wherein the amino acid is a cyclic amino acid as recited in claim 1 as amended. However, Torres et al. discloses that inclusion of unusual beta-amino acids into peptides is useful. (p. 16569 left column first paragraph – right column second paragraph) Thee include cyclobutene peptides having amino acids as recited in present claim 11, (p. 5670 chart 1) as well as beta amino acids having a cyclobutyl in the side chain as recited in claim 6. (p. 5670 scheme 1)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the method of Suga et al. to make acylated tRNAs bearing any of the cyclobutene acids described by Torres et al. One of ordinary skill in the art would have seen the disclosure of Torres et al. as suggesting that producing peptides containing these amino acids is useful, and would have seen the disclosure of Suga et al. as demonstrating generally that a variety of beta-amino acids could be attached to tRNAs in order to be incorporated into peptides.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Suga et al. (US pre-grant publication 2011/0275119, of record in previous action)in view of Estevez et al. (Reference included with PTO-892)
Suga et al. discloses a method of synthesizing a polypeptide comprising using an ARS ribozyme to acylate tRNA with an amino acid, including nonnatural amino acids such as beta-amino acids, gamma- amino acids, and delta- amino acids, among various other amino acids. (p. 2 paragraph 22, p. 4 paragraph 72, also figure 3)
Suga et al. does not disclose an aminoacyl tRNA wherein the amino acid is a cyclic amino acid as recited in claim 1 as amended. However, Estevez et al. discloses that cyclopentane beta-amino acids are attractive candidates for the stabilization of bioactive peptides. (p. 583 left column first paragraph) Estevez et al. further discloses polyhydroxylated cyclopentane beta-amino acids, which would meet the definition of a 5-membered carbocycle substituted with one or more hydroxyl substituents as recited in present claims 1 and 30. (p. 583 scheme 1) One of these beta-amino acids is incorporated into a tripeptide. (p. 586 scheme 6_
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the method of Suga et al. to make acylated tRNAs bearing any of the substituted cyclopentane amino acids described by Estevez et al. One of ordinary skill in the art would have seen the disclosure of Estevez et al. as suggesting that producing peptides containing these amino acids is useful, and would have seen the disclosure of Suga et al. as demonstrating generally that a variety of beta-amino acids could be attached to tRNAs in order to be incorporated into peptides.
Therefore the invention taken as a whole is prima facie obvious.
Response to Arguments
Applicant’s arguments, submitted August 27, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that the secondary references Cabrele, Torres, and Estevez all describe methods of incorporating nonstandard amino acids by chemical synthesis rather than ribosomal translation. This argument in itself is not persuasive. Obviousness does not require that the entire disclosure of a particular claim be found within a single reference. Rather a combination of references that together describe a particular invention is sufficient to render said invention obvious. In the present case, Suga provides much or the necessary motivation because it specifically describes a ribosomal based method for incorporating nonstandard amino acids into proteins that utilizes aminoacyl-tRNAs. This would provide motivation for one of ordinary skill in the art to make aminoacyl-tRNAs for use in this method comprising any nonnatural amino acid that could be useful to incorporate into proteins.
Applicant further argues that there would be no reasonable expectation of success in using the specific claimed aminoacyl-tRNAs to incorporate cyclic amino acids into a polypeptide, because these amino acids are not efficiently accepted by the ribosome.
Looking to the evidence of record, the present disclosure (p. 122 paragraph 513 – p. 123 paragraph 516) discloses experiments wherein ribosomal translation was used to incorporate a nonstandard amino acid at the N- terminus, C- terminus, or an internal position of a polypeptide. P. 119 paragraph 502 further discloses that translating polypeptides using these aminoacyl-tRNAs can incorporate a nonstandard amino acid into the N-terminus of a polypeptide but not into the C-terminus or an internal position. Pp. 119-120 paragraphs 503-504 further disclose that the use of an engineered ribosome to improve incorporation of these amino acids into polypeptides. In particular, this engineered ribozyme is capable of incorporating nonstandard aminoacyl-tRNAs at the C-terminus or internal positions in the polypeptide, rather than just at the N-terminus. Based on this disclosure, a process of translating a protein using a nonstandard aminoacyl-tRNA and said engineered ribosome would be nonobvious over the cited art, as would a process that specifically incorporates the aminoacyl-tRNA into an internal or C-terminal position of a growing polypeptide rather than using it as the N-terminal initiator.
However, the elected invention under prosecution is not an engineered ribosome or a process for translating a polypeptide, but rather is directed to the aminoacyl-tRNA itself. Therefore the mere fact that Applicant has discovered a more effective way of using said nonstandard aminoacyl-tRNA does not make the aminoacyl-tRNA itself nonobvious if there is still some reason in the prior art for one of ordinary skill in the art to make said molecule. Looking to the reference Suga et al., the authors of this reference recognize the aforementioned difficulty, and specifically describe using nonstandard aminoacyl-tRNAs as initiators to incorporate a nonstandard amino acid or small peptide containing such an acid at the N-terminal of an in vitro translated polypeptide. (p. 1 paragraph 12 – p. 2 paragraph 14, p. 2 paragraph 22) According to Applicant’s own disclosure as discussed above, native ribosomes are in fact capable of substituting a nonstandard amino acid at the N-terminal initiator position, and there would be no reason to doubt the enablement of Suga’s invention and its applicability across a wide variety of different nonstandard amino acids, including the claimed cyclo-alkyl beta-amino acids.
For these reasons all of the above rejections are deemed proper and maintained.
Conclusion
Claims 1, 11, 27, 28, 30, and 31 are rejected. Claims 29 and 32 are objected to for depending from a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claims and any intervening claims. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 10/7/2026
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