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 .
Application Status
Claims 1, 5, 23, 40, 47, 59, 62, 65-66, and 82 are pending and examined on the merits herein.
Grounds of Rejection Withdrawn
Previous objections to the specification are withdrawn in view of amendments.
Previous objection to claim 82 is withdrawn in view of amendments.
All previous objections and rejections of claims 2-4, 6-12, 14, 20, 24, 28, 32, 35, and 38 are rendered moot by claim cancellation.
Previous rejection of claims 5 and 23 under 35 U.S.C. 112(b) are withdrawn in view of claim amendments.
Previous rejection of claim 23 under 35 U.S.C. 112(a) are withdrawn in view of claim amendment.
Previous rejection of claims 1, 40, 47, 62, and 66 under 35 U.S.C. 102 are withdrawn in view of claim amendment.
Claim Objections
Claim 47 is objected to because of the following informalities:
Claim 47 recites “A cell comprising one of or more of the following: a nucleic acid molecule of claim 1”; the claim should read “A cell comprising the nucleic acid molecule of claim 1”;
Appropriate correction is required.
Claim Rejections - 35 USC § 103
New Rejection Necessitated by Amendment
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 5, 23, 40, 47, 62, and 65-66 are rejected under 35 U.S.C. 103 as being unpatentable over Ma (WO 2020/077356 A1; cited in OA 01/16/2026), Trager (WO 2020/180882 A1; PTO-892), Chan (US 2017/0051044 A1; cited in OA 01/16/2026) and Olsen (J Biol Chem. 2007 Dec 21;282(51):37191-204; PTO-892).
Regarding claims 1 and 47, Ma teaches an engineered cell comprising: (i) a first chimeric antigen receptor polypeptide comprising a first antigen recognition domain; a first signal peptide; a first hinge region; a first transmembrane domain; a first co-stimulatory domain; and a first signaling domain; (ii) at least one cytokine selected from the group consisting … IL-15, IL-l5/IL-l5sushi, IL-15/IL- 15 sushi anchor…and (iii) at least one chemokine (claim 1). Ma further teaches that the target surface cell antigen is PSCA (page 50, lines 18-19). Ma further teaches the present disclosure further provides a polynucleotide encoding the chimeric antigen receptor polypeptide (page 53, lines 11-12) and embodiments of CAR engineered cells that include secreting IL-15/ IL-15 sushi and corresponding polynucleotide (page 172, lines 15-17). Ma further teaches that each unit of CAR bears a scFv against the antigen, a hinge domain (H), a transmembrane domain (TM), a co-stimulatory domain (including, but not limited to, CD28 or 4-1BB) and the intracellular signaling domain CD3 zeta chain (page 22, lines 3-6). Ma further teaches a CAR construct with a SEQ ID NO: 50 (page 64, line 7), which has 100% sequence identity to the instant claimed SEQ ID NO: 8, 18, 22, and 31 and 98.2% sequence identity to the instant claimed SEQ ID NO: 21 which comprises a single amino acid deletion in the instant claimed sequence.
Regarding claims 40 and 47, Ma teaches sorted NK-92 cells or T cells transduced with various CAR- IL15 lentiviral vectors (Figure 65A), and that NK cells co-expressing IL-15/IL- l5sushi can extend survival for a long period of time (page 61, lines 15-16).
Regarding claim 62, Ma teaches a method of treating a cell proliferation disease, said method comprising: administering to a patient in need thereof an engineered cell according to any one of claims 1-14 (claim 15), wherein said cell proliferation disease comprises soft tissue tumor or solid tumor, carcinoma, or sarcoma (claim 16).
Regarding claims 65-66, Ma teaches the present disclosure provides a method of reducing the number of target cells including the steps of (i.) contacting said target cells with an effective amount of an engineered cell having at least one chimeric antigen receptor polypeptide and (ii.) optionally, assaying for the reduction in the number of said cells…wherein the target is PSCA (page 3, lines 24-30). Ma teaches wherein the engineered cell is a T-cell, NKT cell, Natural Killer cell, or NK92 cell (claim 11). Ma further teaches that the cells may be autologous, syngeneic, allogeneic, or xenogeneic to the recipient of the engineered cells (page 60, lines 21-22).
Ma does not teach wherein the PSCA-scFv comprises SEQ ID NO: 32 and 33; or that the IL-15 domain consists of the amino acid sequence SEQ ID NO: 103.
Regarding claim 1, Trager teaches a polynucleotide encoding a CD19-directed chimeric antigen receptor, CAR comprising a CD3 zeta subdomain comprising SEQ ID NO: 8 (claim 11), wherein the encoded mblL15 comprises the amino acid sequence of SEQ ID NO: 12 (claim 13) SEQ ID NO: 8 has 100% sequence identity to SEQ ID NO: 21. SEQ ID NO: 12 has 100% sequence identity to the instant claimed SEQ ID NO: 103. Trager further teaches that in several embodiments soluble IL-15 is used and that the IL-15 domain, e.g. mblL-15 domain, may render immune cells (e.g., NK or T cells) expressing it particularly efficacious against target tumor cells. (para 00175).
Regarding claim 1, Olsen teaches the sequence of hIL15 in Fig 1B which consists of 100% sequence identity to the instant claimed SEQ ID NO: 103. Olsen further teaches that IL-15 is most active when it is presented in cis by membrane-bound IL-15Rα and that soluble IL-15Rα inhibits the activity of IL-15 presumably by competing with membrane-bound IL-15Rα for IL-15 (page 37200, col 2, para 4).
Regarding claim 5, Chan teaches antigen binding constructs that bind the PSCA antigen can be antibodies, minibodies and/or fragments thereof such as scFv, including SEQ ID NO: 127 (para 0283), SEQ ID NO: 127 has 100% sequence identity to the instant claimed SEQ ID NO: 32 and 33.
Regarding claim 23, Chan teaches scFv linker sequence comprising SEQ ID NO: 64, therefore teaching 100% of the instant claimed SEQ ID NO: 40.
Regarding claim 65, Chan further teaches provided herein are methods for treating a subject having cancer, or inhibiting the growth of a prostate cancer cell expressing a Prostate Stem Cell Antigen (PSCA) protein comprising contacting the cancer cell (e.g., prostate, bladder, pancreatic cancer cell, with a construct as provided herein, in an amount effective to inhibit the growth of the cancer cell (para 0370).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to use the scFv sequences as taught by Chan, with the CD3 zeta intracellular signaling domain as taught by Trager, the IL-15 sequence as taught by Trager and Olsen in the PSCA-CAR-IL15 construct as taught by Ma. The ordinary artisan would have been motivated to do so because Chan teaches PSCA targeting scFvs can be used to inhibit the growth of PSCA expressing cancer cells, while Ma and Trager teach chimeric antigen receptors with enhancer constructs including a soluble IL-15 that enhances cell expansion, persistence and enhances the immunotherapy itself. Olsen also teaches that addition of soluble IL-15Rα inhibits the activity of IL-15. The ordinary artisan has a reasonable expectation of success in substituting a known PSCA scFv sequence into the PSCA-CAR-IL15 with the known human IL-15 sequence to promote improved CAR function and persistence and eliminate soluble IL-15R competition for the soluble IL-15.
The rationale to apply a technique taught by the prior art as improving the therapeutic and production characteristics of a similar construct is to predictably obtain an improvement to the second construct and is consistent with the exemplary rationales provided by the Supreme Court in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1395-97 (2007) and discussed in M.P.E.P. § 2143. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Claim 82 is rejected under 35 U.S.C. 103 as being unpatentable over Ma (WO 2020/077356 A1; cited in OA 01/16/2026), Trager (WO 2020/180882 A1; PTO-892), Chan (US 2017/0051044 A1; cited in OA 01/16/2026) and Olsen (J Biol Chem. 2007 Dec 21;282(51):37191-204; PTO-892) as applied to claims 1, 5, 23, 40, 47, 62, and 65-66 above, and further in view of Ueda (Cancer Sci. 2020; 111: 1478–1490; cited in OA 01/16/2026).
The teachings of Ma, Trager, Olsen and Chan regarding claims 1, 5, 23, 40, 47, 62, and 65-66 are detailed above.
Ma, Trager, Olsen and Chan do not teach wherein the NK cells transduced by a vector are stable after one, two or three freeze-thaw cycles.
Regarding claims 82, Ueda teaches generation of NK cells from pluripotent stem cells that express a CAR-tEGFR construct with verified cytotoxicity and cytokine production (abstract). Ueda further teaches generation of a master cell bank suitable for non-clinical testing and clinical trials (section 3.3). Ueda further teaches the frozen iCAR-NK/ILC cells maintained sufficient viability during shipment to a non–clinical test site, approximately 500 km from the production facility, and also maintained cell numbers and viability for 3 hours after thawing, when kept on ice, until injection into the test animals (section 3.3 and Table 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to generate transduced NK cells that are stable through freeze/ thaw cycle as taught by Ueda with the PSCA-CAR- IL15/IL15sushi construct as taught by Ma, Chan and Pinz. The ordinary artisan would have been motivated to do so because Ueda teaches generation of a master cell bank after transduction to use for non-clinical and clinical testing, as well as for shipment to test sites. The ordinary artisan has a reasonable expectation of success to generate freeze/ thaw stable NK cells transduced with the PSCA-CAR-IL15/IL15sushi as a benefit of repeated testing the same lot and ability to ship to different test sites.
Response to Arguments
Applicant's arguments filed 07/16/2026 have been fully considered but they are not persuasive.
Applicant submits: Ma is a very broad disclosure suggesting co-expressing CAR directed any of a variety of targets.
The Office is correct that Ma describes co-expression of a PSCA CAR with IL15/IL15sushi, a fusion protein composed of IL-15 and the sushi domain of IL-15 receptor. Ma explains that the IL-15 sushi domain is a portion of IL-15 Receptor alpha (IL-15Ra). The sushi domain is the IL- 15 binding domain of IL-15Ra (Xq et al. J. Immunol. 167:277-82 (2001).
Present claim 1 is drawn to a "nucleic acid molecule comprising: (i) a first nucleotide sequence encoding a chimeric antigen receptor (CAR)", which is further characterized in claim 1, and "(ii) a second nucleotide sequence encoding an IL-15 domain consisting of the amino acid sequence of SEQ ID NO: 103." SEQ ID NO:103 is a soluble form of human IL-15. Thus, the nucleic acid molecule of the present claim differs from that in Ma at least in that it does not include the sushi domain of IL-15 Ra. It appears that in all of the examples in Ma relating to PSCA CAR co- express the CAR with IL 15/IL 15sushi rather.
Thus, one seeking to modify the PSCA-CAR-tEGFR-IL15/IL15sushi construct of Ma using the teachings of Chan, one would need to at least eliminate the IL-15sushi domain, a domain which Ma states increases the half-life of IL-15 up to 10-fold (Ma at [0325]) and then further modify the construct with the scFv of Chan. The Office did not cite a motivation or reason for eliminating at the sushi domain of Ma. Thus, the Office has not established a prima facie case of obviousness. Moreover, the Office has failed to demonstrate that in combining the teachings of the cited prior art one would have a reasonable expectation of success in practicing the claimed methods.
In Response: This limitation is addressed in the updated 103 rejection detailed above. The Ma reference further teaches that soluble IL-15RA or ILl5sushi profoundly potentiates IL-15 functional activity by prevention of IL-15 degradation soluble IL-15/IL-15RA or IL-l5/IL-l5sushi complexes are stable and much more stimulatory than IL-15 alone in vivo ( In a separate disclosure the Ma group (referred to above as Pinz for clarity) also disclosed a soluble IL-15 and described benefits thereof.
Double Patenting
New Rejections Necessitated by Amendment
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, 23, and 47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, and 11 of U.S. Patent No. 11,466,097 in view of DeRenzo (Front Immunol. 2019 Feb 15;10:218; cited in OA 01/16/2026) and Olsen (J Biol Chem. 2007 Dec 21;282(51):37191-204; PTO-892).
Regarding claims 1 and 5, the patented claims teach a nucleic acid molecule encoding a chimeric antigen receptor comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 26, 28, 30, 32, 34 and 36 (claim 1, 4-5, and 11). SEQ ID NO: 26 has 100% sequence identity to the instant claimed SEQ ID NO: 12, 16, 21, 24, 32, and 33.
Regarding claim 23, SEQ ID NO: 26 has 97.4% sequence identity to the instant claimed SEQ ID NO: 1, with 5 amino acids changed in the linker.
Regarding claim 47, the patented claims teach a population of human T cells comprising a nucleic acid encoding a chimeric antigen receptor comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 26, 28, 30, 32, 34 and 36 (claims 2-3 and 8).
The patented claims do not teach a second nucleotide molecule encoding an IL-15 domain.
Regarding claim 1, DeRenzo teaches constitutively expressed IL-15 can be engineered by tethering IL-15 to the cell membrane or secreted by modified T cells and that CAR T cells modified to secrete IL-15 demonstrated superior proliferative capacity and antitumor activity in vitro and in vivo compared to the CAR alone (page 4, column 1, para 4; Fig 2D). DeRenzo further teaches that after 4 weeks IL-15 expressing CAR T cells had greater activity indicating that IL15 improved T cell persistence over a prolonged period of time (page 4, column 1, para 4; Fig 2D).
Regarding claim 1, Olsen teaches the sequence of hIL15 in Fig 1B which consists of 100% sequence identity to the instant claimed SEQ ID NO: 103. Olsen further teaches that IL-15 is most active when it is presented in cis by membrane-bound IL-15Rα and that soluble IL-15Rα inhibits the activity of IL-15 presumably by competing with membrane-bound IL-15Rα for IL-15 (page 37200, col 2, para 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to add an IL-15 nucleotide as taught by DeRenzo to the PSCA-CAR construct in T cells as taught by the patented claims. The ordinary artisan would have been motivated to do so because DeRenzo teaches that CAR T cells modified to secrete IL-15 demonstrated superior proliferative capacity and antitumor activity in vitro and in vivo compared to the CAR alone, as well as improved persistence. The ordinary artisan has a reasonable expectation of success in adding a known IL-15 nucleotide to the PSCA-CAR T cells to improve performance and longevity of immunotherapy.
The rationale to apply a technique taught by the prior art as improving the therapeutic and production characteristics of a similar construct is to predictably obtain an improvement to the second construct and is consistent with the exemplary rationales provided by the Supreme Court in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1395-97 (2007) and discussed in M.P.E.P. § 2143. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Claims 1, 5, 47 and 62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-36 and 38-42 of U.S. Patent No. 12,565,535 in view of DeRenzo (Front Immunol. 2019 Feb 15;10:218; cited in OA 01/16/2026) and Olsen (J Biol Chem. 2007 Dec 21;282(51):37191-204; PTO-892).
Regarding claims 1 and 5, the patented claims teach a nucleic acid molecule encoding a chimeric antigen receptor (CAR) selected from the group consisting of: a CAR comprising a PSCA scFV (claim 29), wherein the CAR comprises: PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21 (claim 30-32 and 38-41). SEQ ID NO: 38 has 100% sequence identity to the instant claimed SEQ ID NO: 32 and 33. SEQ ID NO: 16, 21, 24, has 100% sequence identity to the instant claimed same SEQ ID NOs.
Regarding claim 47, the patented claims teach a population of human T cells comprising a nucleic acid encoding a CAR selected from the group consisting of: a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21 (claims 33-36).
Regarding claim 62, the patented claims teach a method for treating a human patient having a cancer expressing prostate specific antigen, the method comprising administering to the patient the population of human T cells of claim 33 (claim 42).
The patented claims do not teach a second nucleotide molecule encoding an IL-15 domain.
Regarding claim 1, DeRenzo teaches constitutively expressed IL-15 can be engineered by tethering IL-15 to the cell membrane or secreted by modified T cells and that CAR T cells modified to secrete IL-15 demonstrated superior proliferative capacity and antitumor activity in vitro and in vivo compared to the CAR alone (page 4, column 1, para 4; Fig 2D). DeRenzo further teaches that after 4 weeks IL-15 expressing CAR T cells had greater activity indicating that IL15 improved T cell persistence over a prolonged period of time (page 4, column 1, para 4; Fig 2D).
Regarding claim 1, Olsen teaches the sequence of hIL15 in Fig 1B which consists of 100% sequence identity to the instant claimed SEQ ID NO: 103. Olsen further teaches that IL-15 is most active when it is presented in cis by membrane-bound IL-15Rα and that soluble IL-15Rα inhibits the activity of IL-15 presumably by competing with membrane-bound IL-15Rα for IL-15 (page 37200, col 2, para 4).
It would have been obvious to one of ordinary skill in the art to add an IL-15 nucleotide as taught by DeRenzo that consists of the sequence of human IL-15 as taught by Olsen to the PSCA-CAR construct in T cells as taught by the patented claims. The ordinary artisan would have been motivated to do so because DeRenzo teaches that CAR T cells modified to secrete IL-15 demonstrated superior proliferative capacity and antitumor activity in vitro and in vivo compared to the CAR alone, as well as improved persistence. The ordinary artisan has a reasonable expectation of success in adding a known IL-15 nucleotide to the PSCA-CAR T cells to improve performance and longevity of immunotherapy.
The rationale to apply a technique taught by the prior art as improving the therapeutic and production characteristics of a similar construct is to predictably obtain an improvement to the second construct and is consistent with the exemplary rationales provided by the Supreme Court in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1395-97 (2007) and discussed in M.P.E.P. § 2143. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Claims 1, 5, 47, 62, and 65-66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5-6, 13, 16-18, 20 and 23 of copending Application No. 18/981,030 (reference application) in view of DeRenzo (Front Immunol. 2019 Feb 15;10:218; cited in OA 01/16/2026) and Olsen (J Biol Chem. 2007 Dec 21;282(51):37191-204; PTO-892).
Regarding claims 1 and 47, the copending claims teach a population of cells comprising NKT cells (NKT cells) harboring: (a) a nucleic acid molecule encoding both: a chimeric antigen receptor (CAR), the CAR comprising: a single chain variable domain (scFv) targeting prostate stem cell antigen (PSCA), a spacer, a transmembrane domain, a co-stimulatory domain, and a CD3ζ; signaling domain; and polypeptide comprising a human IL-15 domain that binds to IL-15 receptor; or (b) a first nucleic acid molecule encoding a chimeric antigen receptor (CAR), the CAR comprising: a single chain variable domain (scFv) targeting prostate stem cell antigen (PSCA), a spacer, a transmembrane domain, a co-stimulatory domain, and a CD3ζ; signaling domain and second nucleic acid molecule encoding a polypeptide comprising a human IL-15 domain that binds to rL-15 receptor wherein the scFv comprises a variable heavy chain (BC) and a variable light chain (LC), wherein the BC comprises complementarity-determining regions: CDRH1 comprising the amino acid sequence of SEQ ID NO: 50, CDRH2 comprising the amino acid sequence of SEQ ID NO: 51 and CDRH3 comprising the amino acid sequence of GGF, and wherein the LC comprises complementarity-determining regions: CDRL1 comprising the amino acid sequence of SEQ ID NO: 53. CDRL2 comprising the amino acid sequence of SEQ ID NO: 54, and CDRL3 comprising the amino acid sequence of SEQ ID NO: 55 (claim 1), wherein: (a) the spacer comprises or consists of the amino acid sequence of any of SEQ ID NOs: 3-12 and 28; (b) the transmembrane domain comprises or consists of the amino acid sequence of any of SEQ ID NOs: 13-20 and 34; (c) costimulatory domain comprises or consists of the amino acid sequence of any of SEQ ID NOs: 22-26; (d) the spacer comprises or consists of the amino acid sequence of any of SEQ ID NOs: 3-12 and 28; the transmembrane domain comprises or consists of the amino acid sequence of any of SEQ ID NOs: 13-20 and 34; costimulatory domain comprises or consists of the amino acid sequence of any of SEQ ID NOs: 22-26; and the CD3ζ signaling domain comprises or consists of the amino acid sequence of SEQ ID NO: 21 or a variant thereof selected from SEQ ID NOs: 56-62 (claim 6), wherein the cells comprise a nucleic acid molecule encoding a PSCA CAR followed by a skip sequence, a signal sequence and an IL-15 domain wherein the PSCA CAR includes a signal sequence (claim 16). SEQ ID NOs: 12-13 and 21-22, have 100% sequence identity to the same SEQ ID NO in the instant claims. Instant claimed SEQ ID NO: 33 has 100% sequence identity to SEQ ID NO: 50, 51, and GGF. Instant claimed SEQ ID NO: 32 has 100% sequence identity to SEQ ID NO: 53-55.
Regarding claim 5, the copending claims teach the population of cells of claim 1 or claim 2, wherein the scFv comprises or consists of the amino acid sequence of SEQ ID NOs: 1, 40, or a variant thereof (claim 5). SEQ ID NO: 1 has 100% sequence identity to the instant claimed SEQ ID NO: 32 and 33.
Regarding claims 62, the copending claims teach a method for treating a cancer or a solid tumor that expresses PSCA in a human subject in need thereof, comprising administering the subject a therapeutically effective composition comprising the population of cells of claim 17 (claim 18).
Regarding claim 65, the copending claims teach wherein the solid tumor or cancer is any one or more of: a gall bladder cancer, a gall bladder adenocarcinoma, a pancreatic cancer, a PSCAexpressing NSCLC, a prostate cancer, a urinary bladder cancer, a cervical cancer, an esophageal cancer, or a gastric cancer (claim 23), wherein the cells comprise natural killer cells (NK cells), natural killer T cells (NKT cells) or both (claim 17).
Regarding claim 66, the copending claims teach a method of reducing PSCA-positive cells in a human subject comprising administering the subject a composition comprising the population of cells of claim 17 (claim 20), wherein the cells comprise natural killer cells (NK cells), natural killer T cells (NKT cells) or both (claim 17).
The copending claims do not teach the sequence of the IL-15 domain.
Regarding claim 1, DeRenzo teaches constitutively expressed IL-15 can be engineered by tethering IL-15 to the cell membrane or secreted by modified T cells and that CAR T cells modified to secrete IL-15 demonstrated superior proliferative capacity and antitumor activity in vitro and in vivo compared to the CAR alone (page 4, column 1, para 4; Fig 2D). DeRenzo further teaches that after 4 weeks IL-15 expressing CAR T cells had greater activity indicating that IL15 improved T cell persistence over a prolonged period of time (page 4, column 1, para 4; Fig 2D).
Regarding claim 1, Olsen teaches the sequence of hIL15 in Fig 1B which consists of 100% sequence identity to the instant claimed SEQ ID NO: 103. Olsen further teaches that IL-15 is most active when it is presented in cis by membrane-bound IL-15Rα and that soluble IL-15Rα inhibits the activity of IL-15 presumably by competing with membrane-bound IL-15Rα for IL-15 (page 37200, col 2, para 4).
It would have been obvious to one of ordinary skill in the art to use the human IL-15 sequence as taught by Olsen in the PSCA-CAR with IL-15 construct in T cells as taught by the copending claims for improvement of the T cells as taught by DeRenzo. The ordinary artisan would have been motivated to do so because DeRenzo teaches that CAR T cells modified to secrete IL-15 demonstrated superior proliferative capacity and antitumor activity in vitro and in vivo compared to the CAR alone, as well as improved persistence. The ordinary artisan has a reasonable expectation of success in adding a known IL-15 nucleotide to the PSCA-CAR T cells to improve performance and longevity of immunotherapy.
The rationale to apply a technique taught by the prior art as improving the therapeutic and production characteristics of a similar construct is to predictably obtain an improvement to the second construct and is consistent with the exemplary rationales provided by the Supreme Court in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1395-97 (2007) and discussed in M.P.E.P. § 2143. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 07/16/2026 have been fully considered but they are not persuasive.
Applicant Submits: Claim 1 has been amended in the present response. Applicant, therefore, respectfully requests reconsideration of the non-statutory double patenting rejections.
In Response: Applicant should submit an argument under the heading “Remarks” pointing out disagreements with the examiner’s contentions. Applicant must also discuss the references applied against the claims, explaining how the claims avoid the references or distinguish from them.
Conclusion
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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/AMBER K FAUST/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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