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 amendments, filed 12/03/2025, is acknowledged.
Claim 1-22 are currently pending.
Claims 8-12 and 16-20 stand withdrawn, and claims 3, 13, 14, 21, and 22 (all newly added or amended) are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species.
Claims 1, 2, 4-7, and 15 are under examination as reading on the invention of an antigen receptor comprising a GITRL domains and the Species of a CAR.
In view of the amendments and remarks filed on 12/23/2025, the following rejections remain.
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 1, 2, 4-7, and 15 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 1, 2, 4-7, and 15 are rejected under 35 U.S.C. 112(a) for the same reasons set forth in the Office Action mailed on 9/25/2025. Briefly, the claims encompass a broad genus of polypeptides with little to no structure and the recited function of “GITRL domain”, and there is insufficient written description support in the specification for such a broad genus of polypeptides.
Applicant’s remarks, filed on 12/23/2025, have been fully considered, but have been found to be not convincing. Applicant argues (remarks filed 12/23/2025 pg. 9):
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This has been found to be not convincing. While the instant specification discloses that GITRL sequences from various organisms are known, and SEQ ID NO: 4 is a representative example, the instant claims encompass a much broader genus of polypeptides with any amino acid sequence, all with the function of “GITRL domain”.
For example, the instant claims encompass a genus of polypeptides with at least 5% sequence variation from instant SEQ ID NO: 4 (for example, see withdrawn instant claim 22). A polypeptide having 95% sequence identity with the polypeptide of SEQ ID NO: 1 allows for any combination of 9 amino acid modifications within SEQ ID NO: 4 (9 = 0.05x199; SEQ ID NO: 4 has 199 amino acids). The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19A/(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions.
Thus, the total number of variants of the polypeptide of SEQ ID NO: 4 having 95% sequence homology to the polypeptide of SEQ ID NO: 4 that result solely from substitutions is 199!x19(9)/(199-9)!/9! or over 69,657,024,793,248,018,846,720 variants, all with the function of “GITRL domain”. As stated in the Office Action mailed on 9/25/2025, the single representative species of SEQ ID NO: 4 does not sufficiently represent the broadly claimed genus of polypeptides with the function of “GITRL domain” in the claims.
Additionally, there is insufficient structural identifying characteristics or structure-function relationship either in the instant specification or the prior art to support a broad genus of polypeptides with little to no structure and the function of “GITRL domain”.
As stated in the Office Action mailed on 9/25/2025, Zhou et al. (Natl Acad Sci US A. 2008 Apr 8;105(14):5465-70. doi:10.1073/pnas.0711350105. Epub 2008 Mar 31, in Office Action mailed on 9/25/2025) teaches that there are critical regions on hGITRL that regulate ligand oligomerization, binding to GITR, and activation of downstream signaling (Abstract). Zhou et al. found that removing the last three C-terminal residues of human GITRL reduced protein oligomerization and its biological activity by reducing receptor binding and subsequent downstream signaling (pg. 5467, Figures 1 and 5). Furthermore, Zhao et al. (Cell Rep. 2021 Sep 21;36(12):109734. doi: 10.1016/j.celrep.2021.109734) identified residue 149 as critical for binding of GITRL to its receptor GITR, as a N149A mutant significantly reduced binding of GITRL to GITR, while another mutation, N106A, did not appreciably affect ligand receptor binding (pg. 6 and Figure 3).
Additionally, Bossen et al. (J Biol Chem. 2006 May 19;281(20):13964-71. doi: 10.1074/jbc.M601553200. Epub 2006 Mar 17) teaches that while other ligands interact with cognate receptors from different species, human and mouse GITRL have species-specific interactions (Abstract): “[t]he study revealed that ligand-receptor pairs are either cross-reactive between human and mouse (e.g. Tweak/Fn14, RANK/RANKL), strictly species-specific (GITR/GITRL), or partially species specific (e.g. OX40/OX40L, CD40/CD40L)…”
Therefore, while applicant argues (remarks filed 12/12/2025 pg. 9) “the amino acid sequences of GITRL derived from various organisms is known”, this is an insufficient relationship between a polypeptide’s structure and the function of “GITRL domain”. Undue experimentation is required by one with ordinary skill in the art would not know which polypeptide variants encompassed by the instant claims would retain binding to human GITR (as human GITRL as represented by instant SEQ ID NO: 4 is species-specific), and thus the function of “GITRL domain”, and which polypeptide variants would no longer bind to GITR and thus have the function of “GITRL domain”.
Claims 1, 2, and 4-7 do not meet the requirements of 35 U.S.C. 112(a) for written description as they are currently written. Amending the claims to recite specific GITRL sequences, such as instant SEQ ID NO: 4, without reciting additional variants of unknown structure, would resolve this issue.
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.
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Claims 1, 2, 4, and 6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-13 and 22-29 of copending Application No. 17/631,745 (herein App ‘745, in Office Action mailed on 9/25/2025). Although the claims at issue are not identical, they are not patentably distinct from each other. This is a new ground of rejection necessitated by Applicant’s amendments.
App '745 claims a chimeric antigen receptor comprising an anti-GD2 scFv, a transmembrane domain, and a TCR intracellular domain (claim 11). App '745 additionally claims the CAR further comprising a GITRL domain fused to the C-terminus of the core domain via a self-cleaving peptide domain (i.e., "closer to the C-terminus"; claim 25), anticipating instant claims 1, and 2.
App '745 further claims the CAR having a core domain the further comprises an intracellular domain of a co-stimulator (i.e., the limitations of instant claim 4, App '745 claim 24).
In determining the scope of the definition of “self-cleaving peptide domain” in claim 25, the instant specification of App ‘745 is consulted (¶[0070]): “[i]n the present specification, the phrase “self-cleaving peptide” refers to a peptide sequence with cleavage activity…Examples of self-cleaving peptides include 2A peptides…the self-cleaving peptide can be selected from the group consisting of 2A peptides derived from foot-and-mouth disease (FMDV) (F2A), 2A peptides derived from equine rhinitis A virus (ERAV) (E2A)…”
Thus, the scope of “self-cleaving peptide domain” in claim 25 includes 2A peptides such as E2A, anticipating the limitations of instant claims 6 and 15.
The invention encompassed by App ‘745 anticipates the invention encompassed by instant claims 1, 2, 4, 6, and 15. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 4-7, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-13 and 22-29 of copending Application No. 17/631,745 (App ‘745, supra) in view of Kochenderfer et al. (J Immunother. 2009 Sep;32(7):689-702. doi: 10.1097 /CJI.0b013e318 lac6138, in Office Action mailed on 9/25/2025). This is a new ground of rejection necessitated by Applicant’s amendments.
The invention claimed by App '745 is discussed supra. App '745 does not claim a CAR comprising an anti-CD19 binding domain and a CD28 co-stimulatory domain (instant claims 5 and 7).
Kochenderfer et al., in the same field of endeavor, teaches anti-CD19 CARs that comprise a anti-CD19 scFv as well as a CD28 costimulatory domain (Figure lA and lB). CAR T-cells comprising the anti-CD 19 CARs were able to efficiently eliminate 96% of CD 19 expressing cells in samples from three different patients with chronic lymphocytic leukemia (pg. 10, ¶2 and Figures 1 and 2).
Kochenderfer et al. additionally teaches that T-cells expressing these CARs will be used the treatment of patients with CD-19 B cell malignancies such as CLL (final ¶ of Discussion), as they show promise in eliminating CD19 tumor cells from patient derived samples.
It would have been obvious to one of ordinary skill in the art, before the effective filing date, to have modified the invention of App '745 to have the anti-CD19 antigen binding domain and CD28 costimulatory domain taught by Kochenderfer et al. with a reasonable expectation of success, as both references teach elements of chimeric antigen receptors that one with ordinary skill would be able to apply to either of the taught CARs. One would have been motivated to make this change for the purposes of making anti-CD19 chimeric antigen receptors with CD28 so-stimulatory domains to treat CD19 expressing B-cell malignancies, such as CLL, in patients.
Thus, the instant invention encompassed by the claims is a prima facie obvious variant of the invention claimed by App '745 in view of Kochenderfer et al. This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims 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