DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s reply filed on 9/22/2025 is acknowledged. Claims 1 and 3-16 are pending. Claim 2 is canceled. Claims 14-16 are withdrawn. No claims have been amended.
3. Claims 1 and 3-13 are under examination.
Priority
4. As indicated in the office action mailed on 6/20/2025, the effective filing date of the claims is 11/9/2022.
Applicant’s petition to accept an unintentionally delayed benefit claim under 37 CFR 1.78(c) is dismissed (see Petition Decision mailed on May 22, 2026).
Rejections Maintained
Claim Rejections - 35 USC § 103
5. 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.
6. Claims 1, 3-4 and 6-13 remain rejected under 35 U.S.C. 103 as being obvious over Feldman et al. (US 2015/0031624 A1, pub. date: 1/29/2015), in view of Zhang et al (Frontiers in Immunology, October 2021, 12: Article 724211, pages 1-9).
Regarding claim 1, Feldman et al. teaches a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular signaling domain (claim 1), wherein the CAR further comprises a costimulatory domain ([0019]), the transmembrane domain is CD8 transmembrane domain (claims 7 and 8). Feldman et al. teaches the transmembrane domain comprises a CD8 amino acid sequence comprising SEQ ID NO:13. The amino acid sequence of SEQ ID NO:13 is 97.6% identical to instant SEQ ID NO:2, see alignment below.
It is noted that the CD8 transmembrane domain of Feldman includes both the hinge and transmembrane domains of CD8, as evidenced by SEQ ID NO:13 (see alignment above). SEQ ID NO:13 differs from instant SEQ ID NO:2 by containing two extra glycine.
Regarding claim 3, Feldman et al. teaches that the antigen binding domain is a single chain variable fragment (scFv) ([0014] and [0015]).
Regarding claim 4, Feldman et al teaches the antigen binding domain binds to CD19 ([0119]).
Regarding claim 6, Feldman et al. teaches that the costimulatory domain is the signaling domain of 4-1BB ([0019]).
Regarding claim 7, Feldman et al. teaches CD3 zeta intracellular signaling domain ([0019]).
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Regarding claim 8, Feldman et al. teaches a nucleic acid encoding a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular signaling domain (claim 14), wherein the CAR further comprises a costimulatory domain ([0019]).
Regarding claim 9, Feldman et al. teaches a recombinant expression vector comprising the nucleic acid (claim 18).
Regarding claim 10, Feldman et al. teaches a host cell comprising the expression vector (claim 20).
Regarding claims 11 and 12, Feldman et al. teaches that the host cell is T cell ([0063]).
Regarding claim 13, Feldman et al. teaches a composition comprising the host cell and a pharmaceutically acceptable carrier ([0067]).
Feldman et al does not teach instant SEQ ID NO:2.
Zhang et al. teaches a chimeric antigen receptor comprising CD19 scFv (antigen binding site), CD8 hinge and transmembrane, 4-1BB (costimulatory domain), and CD3[Symbol font/0x7A] (intracellular signaling domain), wherein two consecutive glycine (GG) in the CD8 hinge has been deleted (page 2, column 2, para 2 and Fig. 1A). Zhang et al. teaches that compare to the second generation (2nd)-CAR T cells, 2nd-GG CAR T cells (two consecutive glycine (GG) in the CD8 hinge has been deleted) reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells in vitro and prolonged survival of mice under high tumor burden in preclinical studies (abstract).
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 modified the CAR of Feldman by deleting the two consecutive glycine in the CD8 hinge region in view of Zhang. One of ordinary skill in the art would have been motivated to do so because Zhang et al. teaches that compare to the second generation (2nd)-CAR T cells, 2nd-GG CAR T cells reduced proinflammatory cytokine secretion without diminishing the specific cytotoxicity toward tumor cells in vitro and prolonged survival of mice under high tumor burden in preclinical studies (abstract). One of ordinary skill in the art would have had a reasonable expectation of success because Zhang teaches how to construct 2nd-GG CAR.
It is noted that CD8 hinge only contains two consecutive glycine. When one deletes the two consecutive glycine in the CD8 hinge region of SEQ ID NO:13, one would have obtained an amino acid sequence which is 100% identical to instant SEQ ID NO:2.
Regarding amended claim 1 which recites “wherein the hinge and transmembrane domain is encoded by a nucleotide sequence comprising the sequence of SEQ ID NO:1”, the claim is drawn to a chimeric antigen receptor (a protein) comprising SEQ ID NO:2. The patentability of a product (in this case a protein, specifically a CAR comprising SEQ ID NO:2) does not depend on its method of production (in this case SEQ ID NO:2 is encoded by SEQ ID NO:1). If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.'' In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). In the instant case, SEQ ID NO:2 encoded by SEQ ID NO:1 is not patentable distinct from prior art SEQ ID NO:13 with two consecutive glycine in the CD8 hinge region deleted.
If the product produced by the method does not produce a structurally distinct product, the process of making the product cannot distinguish the product over the prior art. In the instant case, the prior art teaches a CAR comprising the instant SEQ ID NO:2. The limitation wherein the SEQ ID NO:2 is encoded by SEQ ID NO:1 does not change the fact that SEQ ID NO:2 is identical to the prior art SEQ ID NO:13 with two consecutive glycine in the CD8 hinge region deleted.
7. Claims 1 and 3-13 remain rejected under 35 U.S.C. 103 as being obvious over Feldman et al. (US 2015/0031624 A1, pub. date: 1/29/2015), in view of Zhang et al (Frontiers in Immunology, October 2021, 12: Article 724211, pages 1-9), further in view of Wiltzius et al. (US 20180312588A1, pub. date: 11/1/2018).
The teachings of Feldman and Zhang have been set forth above as they apply to claims 1, 3, 4 and 6-13.
Feldman and Zhang do not teach that the CD19 scFv comprises instant SEQ ID NOs: 4 and 6.
Wiltzius et al. teaches a humanized CD19 scFv (clone JS-scFv) comprising SEQ ID NOs: 14 and 16 ([0027], pages 16-17). Wiltzius teaches that a CAR comprising the CD19 scFv selectively kills tumor cells (Example 3). The amino acid sequences of SEQ ID NOs: 14 and 16 are 100% identical to instant SEQ ID NOs: 4 and 6, respectively.
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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 used the humanized CD19 scFv in making the CAR suggested by Feldman and Zhang as discussed above in view of Wiltzius. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Wiltzius teaches that the CAR comprising the humanized CD19 scFv comprising SEQ ID NOs: 14 and 16 selectively kills tumor cells (Example 3). Moreover, the substitution of one known element (CD19 scFv) for another (CD19 scFv) would have yielded predictable results to one of ordinary skill in the art at the time of invention. All the claimed elements were known in the art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary kill in the art at the time of the invention.
Applicant’s Arguments
The response states that applicant has submitted on October 8, 2024 a declaration under 37 CFR 1.130, establishing that the subject matter of deleting the two consecutive glycines in the CD8 hinge region as disclosed in Zhang was obtained from the inventor of the present application. Hence, Zhang et al. cannot be a valid prior art against the present application. In view of the filed petitions under 37 CFR § 1.78 (c) described above, Applicant submits that the effective filing date of instant claims is June 24, 2022, and Zhang et al. was published within the one-year grace period of the present application. Thus, Zhang et al. cannot be a valid prior art against the present application. Since Feldman et al. by itself do not teach or suggest each and every aspect of the present invention, Applicant respectfully requests that the rejection of claims 1, 3-4, 6-13 under 35 U.S.C. 103 be withdrawn.
Response to Arguments
Applicant’s arguments have been carefully considered but are not persuasive. The Declaration is insufficient to overcome the rejection because Zhang et al (published on 10/2021) was not published within grace period (1 year or less before the effective filing date of a claimed invention), and as such the 102(b)(1)(A) is not applied in this case. The effective filing date of the instant claims is 11/9/2022. Applicant’s petition to accept an unintentionally delayed benefit claim under 37 CFR 1.78(c) is dismissed (see Petition Decision mailed on May 22, 2026).
Double Patenting
8. 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.
9. Claims 1, 3-4 and 6-13 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/050,461, in view of Feldman et al. (US 2015/0031624 A1, pub. date: 1/29/2015).
This is a provisional nonstatutory double patenting rejection.
Claims 1-9 of copending Application No. 18/050,461 disclose an isolated chimeric antigen receptor (CAR) molecule comprising an antigen binding domain, a hinge domain, a transmembrane domain, a costimulatory domain, and an intracellular signaling domain, wherein the hinge domain comprising the amino acid sequence of SEQ ID NO:1, wherein the antigen binding domain is a single chain antibody or single chain antibody fragment, wherein the antigen binding domain binds to a target antigen selected from the group consisting of CD19, CD20, CD22, CD33, CD123, BCMA, CLL1, CD7, CS1, CEA, AFP, PSMA, GPC3, GD2, EGFRVIII, NKG2D, Mesothelin, Claudin 18.2, ROR3, and Mucd, wherein the antigen binding domain binds to CD19 and comprises a scFv comprising the amino acid sequence of SEQ ID NO: 11, wherein the transmembrane domain comprises a transmembrane domain of a protein selected from the group consisting of the alpha, beta or zeta chain of CD8, the costimulatory domain comprises a functional signaling domain of a protein selected from the group consisting of OX40, CD2, CD27, CD28, CDS, ICAM-1, LFA-1 (CD1la/CD18), ICOS (CD278), and 4-1BB (CD137), the intracellular signaling domain comprises an intracellular signaling domain of CD3 zeta, or FcR gamma, or a functional fragment thereof.
Claims 10-11 of the reference application disclose a nucleic acid construct comprising one or more nucleic acid sequences encoding the isolated CAR of claim 1, an expression vector comprising the nucleic acid construct, a cell comprising the expression vector, wherein the cell is an immune cell, the immune cell is a T cell, and a composition comprising the cell and a pharmaceutically acceptable carrier.
SEQ ID NO:1 comprises a CD8 hinge with GlyGly deleted .
The amino acid sequence of SEQ ID NO:11 is 100% identical to residues 14-56 of instant SEQ ID NO:2, see sequence alignment below:
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Claim 7 of copending application disclose CD8 hinge-transmembrane domain.
The claims of copending application does not disclose SEQ ID NO:2.
Feldman et al. teaches a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain, and an intracellular signaling domain (claim 14), wherein the CAR further comprises a costimulatory domain ([0019]). Feldman et al. teaches the transmembrane domain comprises a CD8 amino acid sequence comprising SEQ ID NO:13. The amino acid sequence of SEQ ID NO:13 is 97.6% identical to instant SEQ ID NO:2, see alignment below:
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It is noted that the CD8 transmembrane domain of Feldman includes both the hinge and transmembrane domains of CD8, as evidenced by SEQ ID NO:13 (see alignment above). SEQ ID NO:13 differs from instant SEQ ID NO:2 by two extra glycine.
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 replaced the hinge in SEQ ID NO:13 of Feldman with the hinge of SEQ ID NO:1 of the copending application to arrive the instant SEQ ID NO:2 in view of the claims of copending application and Feldman. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because the claims of copending application teaches using CD8 hinge-transmembrane domain to construct a chimeric antigen receptor, wherein the two consecutive glycine has been deleted.
Regarding this provisional double patenting rejection, Applicant submits that a terminal disclaimer would be submitted when the double patenting rejection is the only rejection remaining in the present application.
Response to Applicant’s Arguments
In the response, Applicant requested that the double patenting rejection be held in abeyance until there are allowable claims in this application and the double patenting rejection is the only remaining rejection.
The rejection is maintained as applicant has not taken any action to resolve the issue.
Conclusion
10. No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HONG SANG/Primary Examiner, Art Unit 1646
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