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 .
Claim Status
Claim 1 is pending.
Claims 2-15 are cancel
Claim 1 has been examined.
Priority
This application is a DIV of 15/570,725 10/30/2017 PAT 12091391
15/570,725 is a 371 of PCT/US2016/030469 05/02/2016
PCT/US2016/030469 has PRO 62/155,333 04/30/2015
Maintained Rejection
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.
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.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO 2015/054658 A1, previously cited 12/24/2024) in view of Blackman et al. (J. AM. CHEM. SOC. 2008, 130, 13518–13519, cited and enclosed in the previous office action).
Claim 1 is drawn to a compound formula as follows.
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Yang et al. teach modified amino acids comprising a tetrazine group in a polypeptide for site-specific conjugation (Abstract). Yang et al. teach modified amino acids comprising a
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tetrazine group introduced into a polypeptide in the presence of orthogonal synthetase and orthogonal tRNA via cell free reaction [00308]. Yang et al. show a tetrazine-containing compound as follows [0087], reading on 3-(6-methyl-s-tetrazin-3-yl)phenylalanine (Tet-v3.0-methyl). Yang et al. further teach R is lower alkyl and V is a single bond [0080, last two lines above 0081].
Yang et al. did not specify R as a substituted or unsubstituted phenyl group.
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Blackman et al. teach tetrazine ligation for a biorthogonal reaction that proceeds with unusually fast reaction rates without need for catalyst (p13518, col 1, para 1; p13518, scheme 1
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shown as follows). Blackman et al. suggest tetrazine moiety beneficially modified with phenyl or substituted phenyl groups in scheme 1 having fast ligation chemistry at site-specific manner (p13518, col 1, para 2), one of ordinary skill in the art would have found it obvious to beneficially modify the alkyl group of R in Yang’s compound shown above [0087] with a phenyl or substituted phenyl group for fast ligation as suggested by Blackman et al., reading on the claimed compound as follows.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to modify the methyl group of Yang’s tetrazine compound with Blackman’s phenyl or substituted phenyl group because Yang et al. teach modified amino acids comprising a tetrazine group in a polypeptide for site-specific conjugation (Abstract) and Blackman et al. suggest tetrazine moiety beneficially modified with phenyl or substituted phenyl groups in scheme 1 having fast ligation chemistry at site-specific manner (p13518, col 1, para 2). The combination would have reasonable expectation of success because both references teach the use of a tetrazine compound for site-specific conjugation.
Applicant’s Argument
Yang does not specify R as a substituted or unsubstituted phenyl group to generate the compound as claimed (Remarks, p4, para 2).
Blackman makes no such teaching with regard to "tetrazine ligation for a biorthogonal reaction" because Blackman only teaches that the cycloaddition of two s-tetrazines and trans-cyclooctene derivatives (Remarks, p4, last two para to p5, para 1-4).
Yang supports the unpredictable nature of genetic encoding with non-canonical amino acids (Remarks, p5, last two para to p6, para 1).
Blackman fails to provide any meaningful teaching regarding the use or effectiveness of 1,4-diphenyl-s-tetrazine (Compound la) for genetic encoding of non-canonical amino acids and no apparent reason for the modification to arrive at a phenyl-substituted tetrazine amino acid and no reasonable expectation of success for using the for site-specific genetic encoding (Remarks, p6, para 2-6 to p8, para 1-5).
Response to Arguments
Applicant's arguments filed 1/23/2026 have been fully considered but they are not persuasive for the reasons as follows.
Applicant’s argument (i) is not persuasive because the rejection is based on Yang et al. in view of Blackman et al., not a single reference of Yang et al. as argued by applicant.
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Applicant’s arguments (ii) and (iii) are not persuasive because (a) Yang et al. teach the use of modified amino acids comprising a tetrazine group and incorporated into a peptide or protein via the amino group and carboxylic group of the tetrazine modified amino acid. Yang et al. teach incorporation of tetrazine modified amino acid into a polypeptide well known in the art [00305], demonstrating incorporation of a tetrazine modified amino acid into a polypeptide with reasonable expectation of success well known in the art. Because Blackman teaches the cycloaddition of two s-tetrazines and trans-cyclooctene derivatives with fast reaction rates without need for catalyst (p13518, col 1, para 1; p13518, scheme 1), one or ordinary skill in the art would have been taught and/or motivated to beneficially select R moiety as a phenyl or substituted phenyl group to generate the claimed compound.
Applicant’s argument (iv) are not persuasive because Blackman teaches the cycloaddition of two s-tetrazines and trans-cyclooctene derivatives with fast reaction rates without need for catalyst (p13518, col 1, para 1; p13518, scheme 1), providing a beneficial reason to modify R moiety of Yang’s tetrazine amino acid analogs with phenyl or phenyl substituted group to enhance the rate of conjugation reaction between the tetrazine moiety and a targeted compound comprising a double bond. Incorporation of a tetrazine modified amino acid into a polypeptide for biorthogonal ligation is well-known in the art as further evidenced by Seitchik et al. (J. Am. Chem. Soc. 2012, 134, 2898−2901) in addition to the cited prior art references of Yang et al.in view of Blackman et al. The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See MPEP 2144 (I).
Examiner’s Note:
Applicant should expect the examiner to maintain the rejection as one of ordinary skill in the art follows the teachings of Yang et al.in view of Blackman et al. would make the claimed compound. A person of ordinary skill in the art is well defined as a person of ordinary creativity able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at ___, 82 USPQ2d at 1396. See MPEP 2141.03 (I).
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.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 of copending Application No. 19/294,141 (the ‘141 application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘141 application disclosed a compound obvious to the instant claim 1.
Claims 1 and 7 of the ‘141 application explicitly show a tetrazine modified amino acid for incorporation into a protein or polypeptide, reading on the instant compound in claim 1 as follows.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Arguments
Applicant submits that the claimed tetrazine amino acid is not anticipated by either the protein (Claim 1) or method for making it (Claim 7) claimed in the reference application. The subject matter of pending Claim 1 is not the same as the subject matter claimed in the reference application.
Response to Arguments
Applicant's arguments filed 1/23/2025 have been fully considered but they are not persuasive for the reasons as follows.
Claims 1 and 7 of the ‘141 application (reference) explicitly show a compound formula structure as follows. One of ordinary skill in the art would “at once envisage” to recognize that the specific compound formula shown in claims 1 and 7 reading on the compound formula in the instant claim 1. A side-by-side comparison of the reference compound to the instant compound is shown as follows.
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[AltContent: textbox (Instant compound )]
Conclusion
No claim is allowed.
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.
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/J.L/Examiner, Art Unit 1658
16-February-2026
/LI N KOMATSU/ Primary Examiner, Art Unit 1658