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 .
Claim Status
Claims 1, 5-6, 14-16 and new claims 34-37 are under consideration in this office action.
Withdrawn Objections/Rejections
Any objection or rejection of record pertaining to cancelled claims 2-4, 7-13, and 17-33 are rendered moot by applicant’s cancellation of said claims.
The rejection of claim 5 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of applicant’s amendment.
The rejection of claims 1 and 14-16 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is withdrawn in view of applicant’s amendment to recite the six specific CDRs of the claimed antibody.
The rejection of claims 1 and 14-16 under 35 U.S.C. 103 as being unpatentable over WO 2016208754 in view of Hedecek et al is withdrawn in view of applicant’s amendment to include a specific anti-GPC1 antibody.
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 1, 5-6, 14-16 and new claims 34-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,122,843 in view of Hudecek et al, published 2013 (IDS from 2/7/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are directed to overlapping subject matter: a CAR comprising the same antigen-binding domain that recognizes GPC1.
Claims 1 and 13-14 of patent ‘843 teach a CAR comprising an anti-GPC1 monoclonal antibody comprised of VH with CDR1-3 of SEQ ID NO: 2 and VL with CDR1-3 of SEQ ID NO: 4 of single-domain antibody comprised of CDR1-3 of SEQ ID NO: 6, as in the CAR of instant claims 1 and 5-6 (same SEQ ID NOs). Claim 15 of ‘843 teaches an anti-GPC1 CAR comprised of a CD8a transmembrane domain, a 4-1BB signaling moiety, and a CD3 zeta signaling domain, as in instant claims 14-16.
Claims of ‘843 do not teach a hinge region as set forth in SEQ ID NO: 7 of claim 1, the CD28 transmembrane domain of SEQ ID NO: 12 of new claim 34, the 4-1BB signaling moiety of SEQ ID NO: 13 of new claim 35, the CD3z signaling domain of SEQ ID NO: 14 of claim 36. ‘842 claims does not teach a CAR of SEQ ID NO: 21.
Hudecek et al teaches CARs directed to ROR, wherein the CAR has a short 12 amino acid IgG4 (Uniport Database: P01861, instant PTO-892) hinge with a S108P substitution, which is identical to the hinge of SEQ ID NO: 7 of instant claim 1. Hudecek compared ROR1-CARs with different IgG4-Fc spacer domains of different lengths and found that short hinge-only extracellular spacer conferred superior lysis of ROR1-positive tumor cells and induction of T-cell effector functions compared with CARs with long spacers of Hinge-CH2-CH3 (Abstract).
Hudecek et al teaches that the CAR is comprised of the 27 amino acid transmembrane domain of human CD28 (Uniprot Database: P10747, instant PTO-892) (pg 3154, column 2, para 4), which is identical to the 27 amino acid CD28 transmembrane domain of instant claim 15.
Hudecek et al teaches that the CAR is comprised of the 42 amino acid cytoplasmic domain of human 4-2BB (Uniprot Database: Q07011, instant PTO-892) (pg 3154, column 2, para 4), which is identical to the 42 amino acid 4-1BB signaling moiety of instant SEQ ID NO: 13 of claim 35.
Hudecek et al teaches that the CAR is comprised of the 112 amino acid cytoplasmic domain of isoform 3 of human CD3z (Uniprot Database: P20963, instant PTO-892) (pg 3154, column 2, para 4), which is identical to the 112 amino acid CD3z signaling domain of SEQ ID NO: 14 of claim 36.
Hudecek et al teaches that the CAR fusion protein is comprised of scFv linked to spacer domain linked to transmembrane domain linked to cytoplasmic domain of 4-1BB linked to the cytoplasmic domain of CD3z (pg 3154, column 2, para 4), as in the CAR of SEQ ID NO: 21.
Given that ‘843 teaches a CAR comprising the claimed GPC1 binding domain, a spacer, a transmembrane domain, signaling moiety, and signaling domain and further given that Hudecek teaches the claimed spacer and the amino acid sequences for the transmembrane domain and intracellular domains, it would have been obvious to one of ordinary skill in the art to use the hinge and other domains of Hudecek et al in the CAR of ‘843. First, it would be obvious to use the amino acid sequence of Hudecek et al in the CAR of ‘843, because substituting one known element for another to obtain printable results is obvious. Regarding the spacer, because there were a finite number of identified and predictable solutions for the spacer at the time the application was filed (i.e. short, intermediate, and long); one of ordinary skill in the art would have a reasonable expectation of successfully identifying the claimed spacer using methods already described in the art. For example, Hudecek teaches that hinge regions of different lengths have different effects on the cytotoxic function of CAR-T cells (Figure 1). Thus, one would use the spacer of Hudecek in the CAR of ‘843 and have a reasonable expectation of success, because Hudecek has demonstrated that customizing spacer design and increasing affinity of CARs enhances T-cell effector function and recognition of tumors by the CAR (abstract). The additional steps of determining spacer length are via methods described in the art (see all of Hudecek). See MPEP 2143.02.II: The court held the claimed method would have been obvious over the prior art relied upon because one reference contained a detailed enabling methodology, a suggestion to modify the prior art to produce the claimed invention, and evidence suggesting the modification would be successful.
Response to Arguments
Applicant's arguments filed March 30, 2026 regarding the rejection on the ground of non-statutory double patenting as being unpatentable over Patent ‘843 in view of Hedecek et al have been fully considered but they are not persuasive.
Applicant indicates that treatment with CAR T cells expressing the claimed CAR with the short hinge exhibits unexpectedly improved efficacy compared to CAR T cells expressing CAR with intermediate or long spacer; thus, the results advantageous results of the claimed CAR could not have been predicted based on the teachings of ‘843 in view of Hedecek et al (remarks, pg 6).
‘843 teaches a GPC1 CAR comprised of an scFv that recognizes GPC1, a spacer, a transmembrane domain, a signaling moiety of 4-1BB, and an intracellular signaling domain of CD3-z. The claims of ‘843 do not teach the spacer. Hudecek et al recognizes the obstacles to be overcome in the development of CARs, especially related to spacer length, and teaches the claimed spacer and other spacers of different lengths (pg 3155, column 2, para 3). Because Hudecek et al suggests a finite number of ways to overcome these obstacles [i.e. short spacer (hinge only), medium spacer (hinge-CH3), and long spacer (hinge-CH2-CH3)] (pg 3155, column 2, para 3) and teaches methods for assessing the ability of CAR-T cells expressing CARs with different spacer lengths to inhibit cytokine production (Figure 1), it would have obvious to one of ordinary skill in the art to test the known spacers in the CAR of ‘843. Further, one would have a reasonable expectation of successfully identifying the optimal spacer in the CAR of ’854.
Not only does Hedecek et al teach the spacer claimed but also teaches the other spacers (i.e. hinge-CH3 and hinge-CH2-CH3) that were investigated by applicant (see remarks pg 6; also Figure 6H of disclosure). An "obvious to try" rationale may support a conclusion that a claim would have been obvious where one skilled in the art is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. " [A] person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under 35 U.S.C. 103." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). The teachings of Hedecek et al demonstrate that the ordinary artisan was aware of the criteria to determine optimization of a CAR comprised of a spacer; further, it was known that these criteria had been met for several other CARs. Thus, it would be conventional and within the skill of one in the art to identify the optimum spacer length for the CAR of ‘834.
Further regarding the claim of unexpected results, case law holds that although the record may establish evidence of secondary consideration which are indicia of nonobviousness, the record may also establish such a strong case of obviousness that the objective evidence of nonobviousness is not sufficient to outweigh the evidence of obviousness. Newell Cos. V. Kenney Mfg. Co., 864 F.2d 757, 769, 9 USPQ2d 1417, 1427 (Fed. Cir. 1988), cert. denied, 493 U.S. 814 (1989). Given the combined teachings of ‘834 and Hudecek et al, the claimed product would have been readily conceived by an ordinary artisan. One looking to optimize the CAR of ‘834 would look to the spacers and methods of Hedecek et al, because it was well known in the art that spacer length is an important factor determining CAR functionality and efficacy.
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.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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