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 .
Applicant’s amendment, filed on 11/20/2025, is acknowledged.
Claims 1-44 and 46-48 are cancelled.
Claims 45 and 49-100 are currently pending.
Claim 45 is the only independent claim.
Claims 53, 54, 67, 70-77, 82-84, 87-94, and 97-99 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species.
Claims 45, 49-52, 55-66, 68, 69, 78-81, 85, 86, 95, 96, and 100 are under examination.
Applicant’s amendments and remarks, filed 11/20/2025, have obviated the 35 U.S.C § 102 rejection in the Office Action mailed 8/20/2025. This rejection is hereby withdrawn.
In view of Applicants arguments and amendments, filed 11/20/2025, the following rejections remain.
Claim Objections
Claims 51, 52, 55-66, 68, 69, 78-81, 85, 95, and 96 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 45, 49, and 50 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention. This is a new grounds of rejection necessitated by Applicant’s amendments.
Claims 45, 49, and 50 stand rejected for the reasons discussed in the Office Action mailed 8/20/2025. Briefly, Applicant does not have sufficient written description to support a genus of TCR Cα and Cβ domain with all of the mutations recited in claims 45, 49, and 50 with the function of “higher unfolding temperature (Tm)” when compared to a corresponding TCR without the mutations in either the Cα and/or Cβ domain.
Applicant’s amendments and remarks, filed 11/20/2025, have been fully considered, but have been found to be not convincing.
Applicant has amended instant claim 45 to recite a first and second polypeptide comprising a TCR Cα domain with F at position 139, I at position 150 and T at position 190, and a Cβ domain with K at position 134, R at position 139, P at position 155, and D or E at position 170 (all Kabat numbering), or the additional mutations in claim 50, when compared to a Cα and/or a Cβ without these mutations. Applicant remarks that the basis for this rejection has been eliminated.
This has been found to be not convincing. The recitation of “and/or” when referring to the TCR Cα and Cβ domains without the recited mutations in the claims leaves these claims without adequate written description support for the function of “higher unfolding temperature (Tm)”.
For example, the instant claim encompasses a genus of TCR Cα and Cβ domains with the mutations recited in claims 45, 49, and 50 with a higher Tm than an identical Cα domain and a Cβ domain without the recited mutations, and a genus TCR Cα and Cβ domains with the mutations recited in the claims with a higher Tm than a Cα without the recited mutations and an identical Cβ.
The instant specification discloses Tm of different TCRs with mutated residues with either all seven of the mutations recited in instant claim 45, or only four mutations, in Table 2. Nowhere in the instant specification is there adequate support demonstrating that a TCR with all of the Cα and Cβ mutations recited in the claims would have a higher melting temperature over a TCR with the recited mutations in either only the Cα or the Cβ domains. Instant table 2 demonstrates that an NY-ESO-1 TCR with only four mutants (Cα with T150I and A190T and a Cβ with E134K and H139R) does not have a lower Tm that the same TCR with all seven recited mutations (Table 2 cropped below):
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110
924
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Greyscale
The 28820s2 mutant has a higher Tm than the 30754s1 mutant (i.e., 59.7 vs 59.5 C), and the average Tm of these two mutants is identical (62.35 C). However, the TCRs with 7 mutations has a higher Tm than a TCR without any of the mutations.
Absent any teaching or structure-function relationships, the skilled in the art cannot determine if a TCR with all of the mutations recited in claims 45, 49, and 50 would have the function of “higher melting temperature (Tm)” when compared to a TCR with all of the recited mutations in only the Cα or the Cβ domains.
Amending instant claim 45 to recite (emphasis added) “…except that:…the Cα domain comprises serine at position 139, threonine at position 150, and alanine at position 190 (residues numbered according to Kabat numbering): and…” instead of “and/or” would resolve this issue.
Claims 86 and 100 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 86 and 100 stand rejected as failing to comply with the enablement requirement for the same reasons recited in the Office Action mailed on 8/20/2025.
Applicant’s amendments and remarks, filed 8/20/2025, have been fully considered, but have been found to be not convincing.
Applicant has amended instant claim 45 to recite a first and second polypeptide comprising a TCR Cα domain with F at position 139, I at position 150 and T at position 190, and a Cβ domain with K at position 134, R at position 139, P at position 155, and D or E at position 170 (all Kabat numbering), or the additional mutations in claim 50, when compared to a Cα and/or a Cβ without these mutations. Applicant remarks that the basis for this rejection has been eliminated.
This has been found to be not convincing.
Applicant’s arguments and amendments did not address the issues brought up in the Office Action mailed on 8/20/2025 for instant claims 86 and 100.
As stated in the Office Action mailed on 8/20/2025, the prior art demonstrates that soluble TCRs are: 1) useful for targeting of therapeutics such as toxins to cells, however the soluble TCR is not able to specifically eliminate cells alone; and 2) specific TCR Vα and Vβ domain pairs recognize specific epitopes, which allow for specific targeting of cells expressing the specific epitope.
For these reasons, undue experimentation would be required by one of ordinary skill in the art to use a method of treatment comprising administration of a broad genus of TCRs comprising the Cα and Cβ of SEQ ID NO: 5 and 7, respectively, wherein generic Vα and Vβ domains are fused to their respective constant domains.
The specification does not reasonable provide enablement to make and use the invention of instant claims 86 and 100.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
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.
Claims 45, 49, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-62 of copending Application No. 19/100,231 (herein App ‘231, in Office Action mailed 8/20/2025). Although the claims at issue are not identical, they are not patentably distinct from each other. This is a new grounds of rejection necessitated by Applicant’s amendments.
Claims 45, 49, and 50 are provisionally rejected as unpatentable over App ‘231 for the same reasons discussed in the Office Action mailed 8/20/2025.
Applicant has amended instant claim 45 to recite a first and second polypeptide comprising a TCR Cα domain with F at position 139, I at position 150 and T at position 190, and a Cβ domain with K at position 134, R at position 139, P at position 155, and D or E at position 170 (all Kabat numbering), or the additional mutations in claim 50, when compared to a Cα and/or a Cβ without these mutations. Applicant remarks that the basis for this rejection has been eliminated.
This has been found to be not convincing.
As stated in the Office Action mailed on 8/20/2025, App ‘231 claims TCRs with Cα and Cβ of SEQ ID NO: 3 and 4, respectively. SEQ ID NO: 4 of App’231 additionally contains the E134K mutation, and therefore meets the limitations of amended claims 45, 49, and 50.
The TCR molecules claimed by App ‘231 anticipate instant claims 45, 49, and 50. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MAHER M HADDAD/Primary Examiner, Art Unit 1641