DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 01/22/2026 has been entered. Claims 19-24 and 34 are cancelled. Claims 1-18, 25-33, and 35 are pending in this application. Claims 1-18, 25, and 27-32 are withdrawn. Claims 26, 33, and 35 are currently under examination.
Priority
This application is a CON of 15/734,182 filed on 12/01/2020, now PAT 11814621, is a 371 of PCT/US2019/035215 filed on 06/03/2019, which claims benefit of US PRO 62/679,350 filed on 06/01/2018.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 62/679,350, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 26 and 33 recite “R is… cycloalkyl, optionally substituted with amino; heterocycloalkyl; alkylheterocycloalkyl… 5-aminomethyl-furan-3-yl… piperidin-4-yl, (piperidin-4-yl)methyl, piperazin-4-yl, and (piperazin-4-yl)methyl”, and/or “R is… 5-aminomethyl-furan-3-yl”, which are not disclosed or supported by the prior-filed Application No. 62/679,350. Thus, the priority date of claims 26, 33, and 35 is 06/03/2019.
Applicant’s Arguments/Remarks filed on 01/22/2026 have been fully considered. Applicant argued “The Priority Document describes methods for preparing tRNA-linked non-canonical substrates… See, e.g., Figures 1-5 of the Appendix I and Figures 1-4 of Appendix II… in accordance with the requirement of Section 112” (p. 8, para. 5).
In response, these arguments are found not persuasive because of the following reasons. The Appendix I and Appendix II listed specific structures, that have different scopes with the claimed generic structures or distinct species. “To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, or 365(c), each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure”. See MPEP 2163.05.
Election/Restrictions
Applicant’s election without traverse of Group IV (claims 26-29) and species (R is 3-hydroxy-4-nitrophenyl,
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) in the reply filed on 12/06/2024 is acknowledged. Since previously examined species “
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, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, and 6-aminohexyl” have been deleted, the search is extended to cycloalkyl, optionally substituted with amino in claim 26. Claims 1-18, 25, and 27-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and invention, there being no allowable generic or linking claim. Thus, claims 26, 33, and 35 are currently under examination.
Withdrawn Claim Rejections
The rejection of claims 26, 33, and 34 under 35 U.S.C. 102(a)(1) as being anticipated by Takahiro, as set forth on pages 5-7 of the Non-Final Rejection mailed on 10/22/2025, is withdrawn in view of amended claims 26 and 33, and cancelled claim 34.
New (necessitated by amendment) Claim Rejections - 35 USC § 102
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 26 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Iqbal et al. (Org. Biomol. Chem., 16:1073-1078, January 2018, hereinafter referred to as Iqbal ‘2018, also listed in IDS filed on 09/18/2023).
With regard to structural limitations “An acylated tRNA (transfer RNA, linked via a 3' terminal ribonucleotide) molecule having a formula defined as:
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, R is selected from cycloalkyl, optionally substituted with amino (claim 26):
Iqbal ‘2018 disclosed ribosomal incorporation of backbone modified amino acids:
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, using an editing-deficient valine-tRNA synthetase (ValRS T222P) to demonstrate ribosomal translation of 11 non-canonical amino acids (ncAA) including cyclic β-amino acids. This enzyme is able to charge constrained β-amino acids (1R,2S) 2-aminocyclohexane carboxylic acid (β-1:
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), (1S,2S) 2-aminocyclohexane carboxylic acid (β-2:
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), and (1S,2S) 2-aminocyclopentane carboxylic acid (β-3:
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) (page 1073, left col., para. 1; page 1074, left col., para. 2).
Thus, these teachings of Iqbal ‘2018 anticipate Applicant’s claim 26.
New (necessitated by amendment)/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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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.
Claims 26, 33, and 35 (including elected 3-hydroxy-4-nitrophenyl,
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, for R) are rejected under 35 U.S.C. 103 as being unpatentable over Takahiro (JP2008193911, published on August 28, 2008 and provided with English translation, hereinafter referred to as Takahiro ‘911, also listed in IDS filed on 09/18/2023) in view of Stewart (Aust. J. Chem., 32, 923-925, 1979, hereinafter referred to as Stewart ‘1979, cited in the previous Office Action).
With regard to structural limitations “An acylated tRNA (transfer RNA) molecule having a formula defined as:
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, R is selected from aryl or cyclohexyl ring” (claim 26):
Takahiro ‘911 disclosed that a carboxylic acid having no amino group, amide bond and hydroxyl group at the α-position is certainly a substrate at the start of translation. When starting tRNA is used as tRNA, the carboxylic acid can be introduced into the protein N-terminus during protein synthesis (page 3/46, para. 4, 5, and 7). The general formula (I) COOH-XY-R1 (I), wherein X is a divalent group, preferably -CH2-; Y is a spacer, preferably contains atoms 2 to 30, more preferably 3 to 8, and linearly bonded. One or more double bonds may be contained in the chain structure. Furthermore, the spacer may have 1 to several, preferably 1 to 5, more preferably 1 to 3, cyclic structures such as a benzene ring and/or a cyclohexyl ring, or the cyclic structure and the linear structure were combined. For example, Y is a divalent group derived from an aromatic hydrocarbon ring (aryl), alkane, alkene or alkyne. Specific examples of Y include, -CH2-, -(CH2)m- (m is 1 to 7), -(CH2)o-NH-CO-(CH2)p- (o is 1 to 7, p is 1 to 5), -O-(CH2)2-O-(CH2)2-, -(CH2)q-C6H4- (q is 1 to 3). R1 is a functional group such as an amino group, a thiol group, a carboxyl group, a hydroxyl group, an aldehyde group, an allyl group or a halogenated alkyl group, preferably an amino group. When Y is CH2 and R1 is an amino group, it may be referred to as aminopropionic acid. To add a carboxylic acid having no amino group, amide bond and hydroxyl group at the α-position to tRNA, dinucleotide (pdCpA) is bound to the carboxyl group of the carboxylic acid. The tRNA (tRNA (-CA)) lacking the CA dinucleotide at the 3 'end can be combined with a ligase such as T4 ligase (page 5/46, para. 3, 4, 6, and 9; page 6/46, para. 2, 3, and 9). Fig. 1A to 1D show carboxylic acids having no amino group, amide bond and hydroxyl group at the α-position, to which TAMRA is bound as a labeling substance. Fig. 1D:
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; FIG. 6 shows an example of a carboxylic acid structure (BODIPY FL-ABC3-pdCpA) bound to pdCpA:
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. Synthesis of TAMRA-aminocarboxylic acid-pdCpA (ABC2-ABC4): 40 μL (88 nmol) of aminocarboxylic acid-pdCpA (for example,
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or
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) and 4 μL (200 nmol) of a 50 mM DMSO solution of 5,6-TAMRA-X-SE were mixed (page 8/46, para. 4 and 10; page 12/46, para. 5). Synthesis of aminocarboxylic acid-pdCpA: To 15 μL (0.66 μmol) of pdCpA in DMF, 5 equivalents of Boc-aminocarboxylic acid cyanomethyl ester was added. Example 2: Introduction of Carboxylic Acid Having No Amino Group, Amide Bond, and Hydroxyl Group at α - Position, to which Labeling Substance is Bound, into N-Terminus of Protein. When a carboxylic acid-tRNA not having an amino group, an amide bond or a hydroxyl group at the α - position to which TAMRA was added was added, a band of streptavidin to which TAMRA was introduced was confirmed. FIG. 8 shows the fluorescence intensity of the streptavidin band (page 12/46, para. 1-3; page 14/46, para. 4).
Takahiro ‘911 did not explicitly disclose the limitation “An acylated tRNA (transfer RNA) molecule having a formula defined as:
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, R is 3-hydroxy-4-nitrophenyl,
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, elected)”, required by claims 26, 33, and 35.
Stewart ‘1979 disclosed that preparation of the proposed amino acid derivatives (3) would best proceed from phenolic components with the carboxyl group protected by the acid-labile 2,4,6-trimethylbenzyl group:
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. The homologues (4) with n = 0 and 1 were intended to provide two series of final anionic active esters (3) with substantially different pKa values. The 2,4,6-trimethylbenzyl derivatives (4) were also used similarly for the preparation of several anionic active esters of adipic (=
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) and sebacic acids (=
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) to obtain derivatives of amino acids (page 923, para. 3, page 924, para. 1 to 2; page 925, para. 2).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the generic cyclic structure with cyclohexyl ring as taught by Takahiro ‘911 or the generic alkylaromatic group, bound to the carboxyl group of dinucleotide (pdCpA) as taught by Takahiro ‘911 with
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in view of Stewart ‘1979, followed by optimization of the position of carboxylic group on the aromatic ring to obtain a unnatural amino acid having no amino group, amide bond and hydroxyl group at the α-position as a substrate at the start of translation because (a) Takahiro ‘911 teaches that a carboxylic acid having no amino group, amide bond and hydroxyl group at the α-position is certainly a substrate at the start of translation. A general formula (I) COOH-XY-R1 (I), wherein X is a divalent group; Y is a divalent group derived from an aromatic or cyclic ring (aryl or cyclohexyl); R1 is a functional group such as an amino group, a carboxyl group, or a hydroxyl group, and (b) Stewart ‘1979 teaches the
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is an acceptable moiety as an amino acid analogue and n is 0 or 1 in the (CH2)nCO2H moiety, described above. Thus, one of skill in the art would have a reasonable expectation that by substituting the generic cyclic structure with cyclohexyl ring as taught by Takahiro ‘911 or the generic alkylaromatic group, bound to the carboxyl group of dinucleotide (pdCpA) as taught by Takahiro ‘911 with
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in view of Stewart ‘1979, followed by optimization of the position of carboxylic group on the aromatic ring to obtain a unnatural amino acid having no amino group, amide bond and hydroxyl group at the α-position as a substrate at the start of translation, one would achieve Applicant’s claims 26, 33, and 35. "Exemplary rationales that may support a conclusion of obviousness include: (B) Simple substitution of one known element for another to obtain predictable results". See MPEP § 2143 [R-01.2024] [I].
Applicant’s Arguments/Remarks filed on 01/22/2026 have been fully considered. Applicant argued “The proposed modification in the Office Action requires a skilled artisan to (i) disregard Takahiro' s explicit teachings by removing part of the amino acid structure ( e.g., X) and connecting -COOH directly to the spacer; (ii) eliminate the fluorescent labeling substance from the final product, which is a key component in Takahiro; and (iii) arbitrarily select the 3-hydroxy-4-nitrophenyl moiety of Stewart cited by the Office Action, which is an intermediate to be further converted to the final product without any demonstrated utility or activity” (p. 9, para. 4).
In response, these arguments are found not persuasive because of the following reasons. As indicated in the references’ disclosures above, the fluorescent labeling of the
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core is to assist in visualization of the introduction of carboxylic acid having no amino group, amide bond, and hydroxyl group at α-position into N-Terminus of protein; and similarly, the hydroxyl group of the core
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is esterized to form an amino acid derivative (3). The combination of Takahiro ‘911 and Stewart ‘1979 suggest attachment of cyclohexyl or nitrophenol directly to carboxylic moiety (n= 0 in the (CH2)nCO2H moiety) that yields an amino acid derivative for incorporation into the N-terminal of a protein. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
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 26 remains provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 , 11, and 28 of copending Application No. 17/904,211 (Jewett et al., the claim set of 11/07/2025). Although the claims at issue are not identical, they are not patentably distinct from each other because Appl ‘211 claims “An acylated tRNA molecule having a formula defined as: .
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wherein: tRNA is a transfer RNA linked via a 3' terminal ribonucleotide; and R has a formula:
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wherein: * indicates points of attachment; n is 0-6; R1 and R2 together form a carbocycle… and alkynyl” (claim 1), “having a formula:
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wherein X is (CH2)m and m is 1, 2, 5, or 6” (claim 11), and “the tRNA molecule is
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…
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(claim 28), which is encompassed by the “R is… cycloalkyl optionally substituted with amino” in claim 26 of this Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Arguments/Remarks filed on 01/22/2026 have been fully considered. Applicant argued “the double patenting rejection over the ‘211 application be held in abeyance” (p. 12, last para.).
In response, the double patenting is thus maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691
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