Prosecution Insights
Last updated: July 17, 2026
Application No. 17/616,948

COMPOSITIONS AND METHODS FOR MAKING HYBRID POLYPEPTIDES

Final Rejection §102§103
Filed
Dec 06, 2021
Priority
Jun 04, 2019 — provisional 62/857,184 +1 more
Examiner
VANHORN, ABIGAIL LOUISE
Art Unit
1636
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Yale University
OA Round
2 (Final)
47%
Grant Probability
Moderate
3-4
OA Rounds
0m
Est. Remaining
69%
With Interview

Examiner Intelligence

Grants 47% of resolved cases
47%
Career Allowance Rate
566 granted / 1207 resolved
-13.1% vs TC avg
Strong +22% interview lift
Without
With
+21.8%
Interview Lift
resolved cases with interview
Typical timeline
3y 8m
Avg Prosecution
69 currently pending
Career history
1282
Total Applications
across all art units

Statute-Specific Performance

§101
0.5%
-39.5% vs TC avg
§103
49.6%
+9.6% vs TC avg
§102
1.6%
-38.4% vs TC avg
§112
4.1%
-35.9% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1207 resolved cases

Office Action

§102 §103
DETAILED ACTION Receipt of Arguments/Remarks and Amendments to the specification filed on February 23 2026 is acknowledged. Claims 2-5, 7, 9-11, 15-17, 19, 22-25, 27-31, 34-35, 37-38, 40, 42-44, 47-48 and 51 were/stand cancelled. Claim 1 was amended. Claims 1, 6, 8, 12-14, 18, 20-21, 26, 32-33, 36, 39, 41, 45-46 and 49-50 are pending. Claims 6, 12-14, 18, 26, 32-33, 36, 39, 41, 45-46 and 49-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 17 2025. Claims 1, 8, 20 and 21 are directed to the elected invention. 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 . Withdrawn Objections/Rejections The amendments to the specification filed February 23 2026 are sufficient to overcome the objection to the specification for nucleotide and/or amino acid sequence disclosure. Specifically, the brief description of the drawings now reflect the SEQ ID NO of the corresponding sequences. The examiner notes that both the specification and the sequence listing have been entered. The amendments filed February 23 2026 are sufficient to overcome the rejection of claims 1-2, 8, 20 and 21 under 35 USC 112(b). Claim 1 was amended to now recite just the transitional phrase comprising and the recitation tRNA-like molecule has been removed. Furthermore the cancellation of claim 2 renders the rejection moot. The amendments filed February 23 2026 are sufficient to overcome the rejection of claims 1, 2 and 8 under 35 USC 102(a)(1) over Servillo et al. and the rejection of claims 1, 2, 8 and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Servillo et al. in view of Ibba et al. The claims as amended exclude the compounds taught in Servillo et al. Support for the current amendment can also be found in Fig. 1D which specifically teaches an unsubstituted amino. The examiner notes that Applicants make no arguments over the combination of Servillo et al. and Ibba et al. but merely that Servillo et al. does not teach the tRNA as now claimed. New Rejections Necessitated by the Amendments filed February 23 2026 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(s) 1 and 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carlomagno et al. (JACS, 1999). The instant application claims a functionalized tRNA comprising a functional molecule comprising a benzoic acid or benzoic acid derivative acylated to the 3’ nucleotide of a natural or engineered tRNA. The functionalized tRNA is of formula II’: PNG media_image1.png 396 596 media_image1.png Greyscale wherein A’ is an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group or a substituted heteroaryl group with the proviso that when the functionalized tRNA has a structure of formula IV: R1 is not an unsubstituted amino group: PNG media_image2.png 511 672 media_image2.png Greyscale . Carlomagno et al. is directed to transferred cross-correlated relations: application to the determination of sugar pucker in an amino acylated tRNA-mimetic weaky bound to EF-Tu. As shown in figure two there are two isomers of the ester of anthranilic acid with adenosine: PNG media_image3.png 275 413 media_image3.png Greyscale (page 1946, paragraph bridging right and left column). 3’-terminal adenosine is taught in the tRNA (page 1948 right column; page 1946). Therefore, Carlomagno et al. teaches replacement of the 3’-terminal adenosine of the tRNA with compound b (2’-Ant-ado). This reads on formula II’ wherein A’ is an amino substituted aryl. This compound, 2’-Ant-Ado does not fall within the scope of the proviso as the aryl ring is attached at the 2’ position whereas the negative proviso is for 3’. Regarding claim 8, the 2’-Ant-ado reads on formula IV’ wherein R1 is an amino group. 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 of this title, 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 1 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Wilkinson et al. (JACS, 2005). Applicant Claims The instant application claims a functionalized tRNA comprising a functional molecule comprising a benzoic acid or benzoic acid derivative acylated to the 3’ nucleotide of a natural or engineered tRNA. The functionalized tRNA is of formula II’: PNG media_image1.png 396 596 media_image1.png Greyscale wherein A’ is an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group or a substituted heteroaryl group with the proviso that when the functionalized tRNA has a structure of formula IV: R1 is not an unsubstituted amino group: PNG media_image2.png 511 672 media_image2.png Greyscale Determination of the Scope and Content of the Prior Art (MPEP §2141.01) Wilkinson et al. is directed to RNA SHAPE chemistry reveals nonhierarchical interactions dominate equilibrium structural transitions in tRNAAsp transcripts. Shown in equation one is the reaction of N-methylisatoic anhydride (MNIA) to form ester adducts at the 3’ position. The reactivity of the 2’-hydroxy group is gated by the underlying local structure such that flexible nucleotides react to form 2’-O-adduct more readily than nucleotides constrained. PNG media_image4.png 155 406 media_image4.png Greyscale . As shown in Figure 7, nucleotides in the T-, D- and anticodon loops and in the 3’-CCA region are reactive (page 4664, right column; page 4662, left column). Ascertainment of the Difference Between Scope the Prior Art and the Claims (MPEP §2141.02) While Wilkinson et al. suggest that the acylation can occur in flexible nucleotides such as the 3’-CCA, Wilkinson et al. does not expressly teach acylation of the 3’-terminal adenosine. Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-2143) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to react the N-methylisatoic anhydride with the terminal 3’-A of the tRNA. One skilled in the art would have been motivated to reach the anhydride with this nucleotide as Wilkinson et al. expressly teaches the 3’-terminal end is a reactive site, specifically pointing to the CCA region of the tRNA. Since there are a limited number of reactive sites, specifically 10 which includes A76 as set forth on page 4662, one skilled in the art would have been motivated to attach the anhydrate to 2’-OH of any of these positions. The examiner notes that the instant claims do not exclude acylation of other nucleotides. Even if the claims were limited, A76, is specifically pointed to by Wilkinson et al. Regarding the claimed structure of claims 1 and 8, as shown in equation 1, attachment of the anhydride at the 2’-OH results in the structure of formula II’ or formula IV’ wherein the base is adenosine and the A’ is a methyl-NH substituted aryl which corresponds to a R1 of amino substituted with an alkyl (aka methyl) group. Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Carlomagno et al. as applied to claims 1 and 8 above and in view of Ibba et al (Genes Dev., 2004, cited in the Office action mailed on 10/21/25). Applicant Claims The instant application claims the tRNA is an imitator tRNA or an elongator tRNA. Determination of the Scope and Content of the Prior Art (MPEP §2141.01) The teachings of Carlomagno et al. are set forth above. The modified tRNA is taught an aminoacylated tRNA mimic (title). Ascertainment of the Difference Between Scope the Prior Art and the Claims (MPEP §2141.02) While Carlomagno et al. teaches a modified tRNA, Carlomagno et al. does not expressly teach the tRNA is an initiator tRNA or an elongator tRNA. However, this deficiency is cured by Ibba et al. Ibba et al. is directed to aminoacyl-tRNAs. Aminoacyl-tRNAs (aa-tRNAs) typically found in the cell can be divided into three main types. The largest group comprises correct pairing of an amino acid and the corresponding tRNA and they serve as substrates for ribosomal translation. The elongator tRNAs are by far the most common. Other translation substrates taught include imitator tRNAs (see table 1) (pages 731, left column and page 732). Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-2143) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the modification taught in Carlomagno et al. with either an initiator tRNA or an elongator tRNA. Carlomagno et al. expressly teaches the modification on a tRNA and that this has aminoacyl-tRNA behavior. As taught by Ibba et al. aminoacyl-tRNAs typically found in the cell can be elongator or initiator tRNAs. Since the tRNA in Carlomagno et al. is taught as possessing aminoacyl-tRNA behavior, one skilled in the art would have a reasonable expectation of success in using the modification with typical aminoacyl-tRNA such as initiator or elongator tRNA. Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Wilkinson et al. as applied to claims 1 and 8 above and in view of Ardell et al. (BMC Genomics, 2016). Applicant Claims The instant application claims the tRNA is an imitator tRNA or an elongator tRNA. Determination of the Scope and Content of the Prior Art (MPEP §2141.01) The teachings of Wilkinson et al. are set forth above. The modified tRNA is taught as having a 3’-terminal CCA, specifically including A76. Ascertainment of the Difference Between Scope the Prior Art and the Claims (MPEP §2141.02) While Wilkinson et al. teaches a modified tRNA, Wilkinson et al. does not expressly teach the tRNA is an initiator tRNA or an elongator tRNA. However, this deficiency is cured by Ardell et al. Ardell et al. is directed to initiator tRNA genes template the 3’CCA end at high frequences in bacteria. All active tRNA molecules must contain a CCA sequence at the 3’ end of he site for amino acid attachment and for interaction with the ribosome during protein synthesis (page 1, first sentence). Fig. 1 (page 4) shows the summarized frequences at which elongator tRNA genes and initiator tRNA genes template 3’-CCA. Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-2143) It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the modification taught in Wilkinson et al. with either an initiator tRNA or an elongator tRNA. Wilkinson et al. expressly teaches a 3’-terminal CCA in the tRNA. As taught by Ardell et al. all active tRNA must contain a CCA sequence at the 3’ end and this sequence occurs in both elongator and initiator tRNA. Since either type of tRNA includes this CCA sequence, one skilled in the art would have a reasonable expectation of success in using the modification with any active tRNA. Conclusion 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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Prosecution Timeline

Dec 06, 2021
Application Filed
Oct 21, 2025
Non-Final Rejection mailed — §102, §103
Feb 23, 2026
Response Filed
Apr 15, 2026
Final Rejection mailed — §102, §103 (current)

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Prosecution Projections

3-4
Expected OA Rounds
47%
Grant Probability
69%
With Interview (+21.8%)
3y 8m (~0m remaining)
Median Time to Grant
Moderate
PTA Risk
Based on 1207 resolved cases by this examiner. Grant probability derived from career allowance rate.

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