DETAILED ACTION
Claims 335-360 are pending in the instant application.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 335-358, drawn to a recombinant nucleic acid molecule comprising a sequence encoding a T cell receptor (TCR) fusion protein (TFP) wherein the TFP comprises: (a) a TCR subunit comprising:(i) at least a portion of a TCR extracellular domain, and (ii) a TCR transmembrane domain, (iii) a TCR intracellular domain, and (b) an antigen binding domain that specifically binds CD70; wherein the TCR subunit and the antigen binding domain are operatively linked; and wherein the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell, and a cell comprising the recombinant nucleic acid molecule in the reply filed on 12/19/2025 is acknowledged. Claims 359-360 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 12/19/2025.
Applicants have also elected without traverse from species group A, amino acid sequence SEQ ID NO: 1236 of the recombinant nucleic acid molecule and from species group B, ScFv as the antigen binding domain of the recombinant nucleic acid molecule. Additionally, applicants have elected SEQ ID NO: 853 of the CDRH1 of the scFv heavy chain variable domain, SEQ ID NO: 906 of the CDRH2 of the scFv heavy chain variable domain, SEQ ID NO: 959 of the CDRH3 of the scFv heavy chain variable domain, SEQ ID NO: 1065 of the CDRL1 of the scFv light chain variable domain, SEQ ID NO: 1118 of the CDRL2 of the scFv light chain variable domain, SEQ ID NO: 1171 of the CDRL3 of the scFv light chain variable domain, and SEQ ID NO: 782 of the linker sequence of the scFv.
Claims 342, 351, and 353-356 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/19/2025.
Therefore, claims 335-341, 343-350, 352-354, 356-358 are under examination in the instant application.
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.
Claim(s) 335-341, 343, 345, and 357-358 are rejected under 35 U.S.C. 103 as being unpatentable over Srinivasan et al. (US2019/0233528A1, filed on 01/31/2019, and published on 08/01/2019), in view of Baeuerle et al. (US2019/0276540A1, filed on 11/22/2017, and published 09/12/2019).
Regarding claim 335, Srinivasan et al. teaches a chimeric antigen receptor (CAR) comprising an antigen binding molecule that specifically binds to CD70 (claim 56 of Srinivasan et al.).
However, Srinivasan et al. fails to teach a recombinant nucleic acid molecule encoding an anti-CD70-TFP.
However, Baeuerle et al. teaches a recombinant nucleic acid molecule comprising a sequence encoding a T cell receptor (TCR) fusion protein (TFP),wherein the TFP comprises:(a) a TCR subunit comprising:(i) at least a portion of a TCR extracellular domain, and(ii) a TCR transmembrane domain,(iii) a TCR intracellular domain wherein the TCR subunit and the antigen binding domain are operatively linked; and wherein the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell (paragraph 0008). Baeuerle et al. further teaches that the TFP T cells induced much lower cytokine concentrations than their CAR T cell counterparts, making them attractive as therapeutics, since excess cytokine production induces undesirable side-effects in patients (paragraph 0614).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the
effective filing date of the claimed invention to have used the construct comprising a recombinant nucleic acid
molecule comprising a sequence encoding a TFP disclosed by Baeuerle et al. to incorporate the nucleic acid
molecule encoding an anti-CD70-antigen binding domain of Srinivasan et al. with a reasonable expectation of
success. One would have been motivated to have done so because the TFP T cells induces much lower cytokine
concentrations than their CAR T cell counterparts, making them attractive as therapeutics, since excess cytokine
production induces undesirable side-effects in patients as taught by Baeuerle et al.
Regarding claim 336: Following discussion of claim 335 above, Baeuerle et al. further teaches that at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit (claim 115 of Baeuerle et al.)
Regarding claim 337-338: Following discussion of claim 335 above, Baeuerle et al. further teaches that at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 epsilon, CD3delta, or CD3 gamma (claim 116 of Baeuerle et al.)
Regarding claim 339: Following discussion of claim 335 above, Baeuerle et al. further teaches that the antigen binding domain is connected to the TCR extracellular domain by a linker sequence (claim 167 of Baeuerle et al.).
Regarding claim 340: Following discussion of claim 339 above, Baeuerle et al. further teaches that the linker sequence comprises (G4S)n, wherein G is glycine, S is serine, and n is an integer from 1 to 4 (claim 168 of Baeuerle et al.)
Regarding claim 341: Following discussion of claim 335 above, Baeuerle et al. further teaches that the antigen binding domain is a single-chain variable fragment (scFv) (paragraph 0250).
Regarding claim 343: Following discussion of claim 335 above, Srinivasan et al. further teaches that a T cell expressing the anti-CD70 CAR inhibits tumor growth when expressed in a T cell (paragraph 0082).
Regarding claim 345: Following discussion of claim 335 above, Baeuerle et al. further teaches that the recombinant nucleic acid comprises a promoter, a leader sequence, a sequence encoding a poly(A) tail, a 3'UTR sequence (claims 133, 359, 361-362 of Baeuerle et al.)
Regarding claims 357-358: Following discussion of claim 335 above, Baeuerle et al. further teaches a human CD8+ or CD4+ T cell comprising the recombinant nucleic acid molecule (paragraph 0091).
Claim(s) 335-341, 343, 345-347, 349-350, 357-358 are rejected under 35 U.S.C. 103 as being unpatentable over Srinivasan et al. (US2019/0233528A1, filed on 01/31/2019, and published on 08/01/2019), in view of Baeuerle et al. (US2019/0276540A1, filed on 11/22/2017, and published 09/12/2019) as applied to claims 335-341, 343, 345, and 357-358 above, and further in view of Ma et al. (US 20190255108 A1, filed on 02/10/2018, and published on 08/22/2019).
Regarding claims 335-341, 343, 345, and 357-358, the teachings of Srinivasan et al. and Baeuerle et al. are set forth in detail above.
Regarding claims 346-347, and 349-350: Following discussion of claim 335 above, Baeuerle et al. further teaches that the recombinant nucleic acid comprises a second sequence encoding a fusion protein comprising a second antigen binding domain (claims 68-69 of Baeuerle et al.). Baeuerle et al. also teaches that the fusion protein is expressed on cell surface when expressed in a cell (claim 14 of Baeuerle et al.). Baeuerle et al. also teaches that the sequence encoding the TFP and the second sequence are included in a single nucleic acid molecule, and the sequence encoding the TFP and the second sequence are operatively linked by a second linker comprising a protease cleavage site (paragraph 0077).
However, Srinivasan et al. fails to teach that second sequence encoding the fusion protein comprises the IL-15 polypeptide or a fragment thereof.
However, Ma et al. teaches an engineered cell having at least one of recombinant IL-15, IL-15RA, IL-15sushi, IL-15/IL-15RA, IL15-RA/IL-15, IL-15/IL-15sushi, IL15sushi/IL-15, functional fragment thereof, and combination thereof; and at least one distinct CAR polypeptide wherein the antigen recognition domain includes CD70 to enhance survival or persistence or proliferation of CAR T for treating cancer in a patient (paragraphs 0457-0458). Ma et al. teaches that it is surprisingly found that CAR co-expression of IL-15/IL-15sushi is important for the longer persistence and enhanced activity of the T cells targeting tumor cells (paragraph 0454).
Therefore, it would have been prima facie obvious to one of the ordinary skills in the art before the
effective filing date of the claimed invention to have modified the recombinant nucleic acid molecule encoding the anti-CD70-TFP of Srinivasan et al. in view of Baeuerle et al. to include a second sequence encoding a fusion protein comprising an IL-15 polypeptide with a reasonable expectation of success. One would have been motivated to have done so because this would help enhancing survival or persistence or proliferation of TFP for treating cancer.
Claim(s) 335-341, 343, 345-350, 357-358 are rejected under 35 U.S.C. 103 as being unpatentable over Srinivasan et al. (US2019/0233528A1, filed on 01/31/2019, and published on 08/01/2019), in view of Baeuerle et al. (US2019/0276540A1, filed on 11/22/2017, and published 09/12/2019), and Ma et al. (US 20190255108 A1, filed on 02/10/2018, and published on 08/22/2019) as applied to claims 335-341, 343, 345-347, 349-350, and 357-358 above, and further in view of (“IL-15Ra amino acid sequence”. Retrieved on 01/06/2026 from Uniprot website https://www.uniprot.org/uniprotkb/Q13261/entry).
Regarding claims 335-341, 343, 345-347, 349-350, and 357-358, the teachings of Srinivasan et al., Baeuerle et al., and Ma et al. are set forth in detail above.
Regarding claim 348, Ma et al. fails to teach the amino acid sequence of IL-15Ra or that the fusion protein comprises amino acids 31-267 of IL-15Ra.
However, Uniprot teaches the amino acid sequence of IL-15Ra
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to have utilized amino acids 31-267 of amino acid sequence of IL-15Ra taught by Uniport as the amino acid sequence of the second fusion protein in the modified recombinant nucleic acid of Srinivasan et al., Baeuerle et al., and Ma et al. as the use of the Uniport’s sequence represents nothing more than the substitution of one amino acid sequence for another with predictable results.
Allowable Subject Matter
Claims 344, 352-354, and 356 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.
Claims 344 and 352 are considered free of prior art for the following reasons:
The closest prior art of record Srinivasan et al. (US2019/0233528A1, filed on 01/31/2019, and published on 08/01/2019) teaches a chimeric antigen receptor (CAR) comprising an antigen binding molecule that specifically binds to CD70 (claim 56 of Srinivasan et al.). However, Srinivasan et al. fails to teach a recombinant nucleic acid molecule encoding an anti-CD70-TFP that comprises a sequence encoding an amino acid sequence having at least 90%, 95%, 98%, 99% or more sequence identity to amino acid sequence of SEQ ID NO: 1236. Also, Srinivasan et al. further fails to teach SEQ ID NO: 959 of the CDRH3 of the scFv heavy chain variable domain and SEQ ID NO: 1171 of the CDRL3 of the scFv light chain variable domain.
Additionally, Baeuerle et al. (US2019/0276540A1, filed on 11/22/2017, and published 09/12/2019) teaches a recombinant nucleic acid molecule comprising a sequence encoding a T cell receptor (TCR) fusion protein (TFP),wherein the TFP comprises:(a) a TCR subunit comprising:(i) at least a portion of a TCR extracellular domain, and(ii) a TCR transmembrane domain,(iii) a TCR intracellular domain wherein the TCR subunit and the antigen binding domain are operatively linked; and wherein the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell (paragraph 0008). However, Baeuerle et al. fails to teach that the recombinant nucleic acid molecule comprises an antigen binding domain that specifically binds CD70. Baeuerle et al. further fails to teach that the recombinant nucleic acid molecule comprises a sequence encoding an amino acid sequence having at least 90%, 95%, 98%, 99% or more sequence identity to amino acid sequence of SEQ ID NO: 1236. Also, Baeuerle et al. fails to teach SEQ ID NO: 959 of the CDRH3 of the scFv heavy chain variable domain and SEQ ID NO: 1171 of the CDRL3 of the scFv light chain variable domain.
Overall, the prior art fails to sufficiently teach or render obvious a recombinant nucleic acid molecule encoding an anti-CD70-TFP comprising the amino acid of SEQ ID NO: 1236, SEQ ID NO: 959 of the CDRH3 of the scFv heavy chain variable domain, and SEQ ID NO: 1171 of the CDRL3 of the scFv light chain variable domain as claimed.
The instant claimed recombinant nucleic acid molecule that comprising a sequence encoding a T cell receptor (TCR) fusion protein (TFP) and an antigen binding domain that specifically binds CD70 is considered allowable in view of the prior art of record, such that a person having ordinary skills in the art, at the time invention was made, would not have envisaged the recombinant nucleic acid molecule of SEQ ID NO: 1236 as currently claimed, nor does the prior art render obvious the product currently claimed.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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Hanan Isam Abuzeineh
/H.I.A./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633