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 .
DETAILED ACTION
The amendment filed May 27, 2026 in response to the Office Action of March 3, 2026 is acknowledged and has been entered.
Claims 76-81, 85, 86, 88, and 91 have been amended.
Claims 83 and 84 have been cancelled.
Claims 92 and 93 have been added.
Claims 76-82, and 85-93 are pending and under consideration.
In view of amendments in the Specification of May 27, 2026, the Specification Objection set forth in the previous Office Action of March 3, 2026 is hereby withdrawn.
In view of claim 107 amendment, the Claim Objection set forth in the previous Office Action of March 3, 2026 is hereby withdrawn.
In view of amendments on claims 79, 81, 85, 87, 88, and 91, the 112(b) rejections set forth in the previous Office Action of March 3, 2026 are hereby withdrawn.
In view of amendment on claim 80, the 112(d) rejection set forth in the previous Office Action of March 3, 2026 are hereby withdrawn.
The amended independent claim 76 limits the cancer and TCRα and TCRβ chains. In view of the amendments and applicant’s arguments, the 112(a) rejections (including Written Description rejection and Scope of Enablement rejection) set forth in the previous Office Action of March 3, 2026 are hereby withdrawn.
In view of Abandonment of Appl. 17/938,577, the Double Patenting rejection over this Application set forth in the previous Office Action of March 3, 2026 is hereby withdrawn.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/27/2026 has been considered and entered by examiner.
Claim Objections
Claim 82 is objected to because of the following informalities: “the cancer” should be “the PRAME-positive cancer” for clarity Appropriate correction is required.
MAINTAINED/MODIFIED REJECTIONS
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 76-82, and 85-93 are rejected under 35 U.S.C. 103 as being unpatentable over Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
Mata teaches engineered T cells can induce immune response ([0039]).
Mata teaches several TCRs including R11P3D3 and R11P3D3KE which binds peptide PRAME-004 (SLLQHLIGL) SEQ ID NO: 147 in a complex with an MHC molecule ([00139], and Table 1). It is noted that R11P3D3KE appears to be the same TCR used in the instant Example 39. As evidenced by instant specification, R11P3D3KE comprises a TCR alpha variable domain of SEQ ID NO: 111 and a TCR beta variable domain of SEQ ID NO: 117; a full length TCR alpha chain of SEQ ID NO: 113 and a full length TCR beta chain of SEQ ID NO: 119 (Table 7 on page 55 of the instant publication US 2023/0192886 A1) and is capable of binding to a peptide of SLLQHLIGL in a complex with HLA-A02 ([0318]-[0326], Example 1, and Example 8 of the instant publication US 2023/0192886 A1). Thus, R11P3D3KE of Mata reads on the TCR of instant claims 76-78 and 93.
Mata teaches a method of preparing T cells for immunotherapy, including activating the T cells, transducing the activated T cells with the vector comprising the TCR, and expanding the transduced T cells ([0042], claims 1-5, and 27).
Mata teaches the T cells may be αβ T cells, and/or γδ T cells ([0043]).
Mata teaches the method of preparing engineered γδ T cells expressing an engineered TCR (Example 2). Mata also teaches the method of engineered αβ T cells expressing an engineered TCR (Example 7).
Mata teaches that the αβ T cells expressing engineered TCR construct are functionally active and specific for antigen-positive target cells, such as inducing IFN-γ expression, Granzyme B expression ([0225-0229], Figs. 26-29, and Example 8)
Mata teaches a method of treating a patient who has cancer comprising administering to the patient a composition the population of expanded T cells, wherein the T cells kill cancer cells that present a peptide (PRAME-positive) in a complex with an MHC molecule on the surface including SEQ ID NO: 147 (SLLQHLIGL), wherein the cancer is selected from the group consisting of non-small cell lung cancer, …, and prostate cancer (claim 35).
Mata teaches that the engineered T cells can be used for treating various cancers, including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma ([0158]).
Mata teaches that the administration regimens for engineered T cells can be adjusted based on the severity and course of the disease or condition, previous therapy, the subject’s health status, weight, and/or response to drugs, and/or the judgement of the treating physician ([0149], [0157]).
Taken together, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE. However, Mata does not teach the T cells are administered at a dose of approximately 1 x 108 to approximately 10 x 1010 cells, or the subject is positive for HLA-A*02.
Heemskerk teaches methods for treating hyperproliferative diseases by inducing an immune response against Preferentially Expressed Antigen of Melanoma (PRAME) antigen; the immune response may be induced by specifically targeting PRAME-expressing cells using T cell receptors directed against PRAME (Abstract and [0003]). The engineered T cells recognizes and binds to a PRAME peptide bound to HLA-A2 on a cancer cell surface, resulting in apoptosis in the tumor cells ([0504]).
Heemskerk teaches isolation of high affinity PRAME specific T cells that recognize the PRAME-derived peptide SLLQHLIGL (SEQ ID NO: 89) (SLL). Heemskerk teaches that the high affinity PRAME specific T cell clones showed high reactivity against a panel of PRAME positive tumor cell lines and against metastatic melanoma, sarcomas, and primary AML cells, and no reactivity against normal cell type ([0507], [1030]). It is noted that the PRAME-derived peptide SLLQHLIGL (SEQ ID NO: 89) is identical to the PRAME-0004 peptide bound by R11P3D3KE.
Heemskerk teaches that human T cells transduced with the pSFG-iC9.2A.PRAME derived Cell A vector. Cell A T cells, comprising the TCR that recognize SLLQHLIGL, are effective against tumors in vivo ([0507]-[0511] and Figs. 4 and 6).
Heemskerk teaches that the effective amount of the engineered T cells may be determined by a physician, considering the individual patient. Factors to be considered may include the extent of the disease or condition, tumor size, extent of infection, metastasis, age, and weight [0391]. For example, the Cell A Dose level can be about 5 x 106 cells/kg (Table 1 on page 34). Thus, for a 60 kg adult, the dose would be 3 x 108 cells which would read on the dose range of the instant claims 76 and 80.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL and HLA-A2 (HLA-A*02) with engineered αβ T cells, and/or γδ T cells expressing the TCR such as R11P3D3KE which recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata and Heemskerk both teach treating cancers (including sarcomas) with said T cells and the T-cells recognize the cells expressing the PRAME antigen bound to HLA-A2 (taught by Heemskerk). Heemskerk further teaches that SLLQHLIGL is expressed in various cancer including sarcomas (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Mata (such as R11P3D3KE ) for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A*02 because these cancers would be targeted by the T cells expressing R11P3D3KE. Based on the antigen-dependent activity of engineered TCR T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising R11P3D3KE would be able to induce immune response against cancers (such as sarcoma) expressing SLLQHLGL and HLA-A*02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claim 79, Mata teaches the method further comprises an adjuvant, such as IL-2 (claim 35-37, [0162]) and adjuvant can enhance or potentiate the immune responses. Regarding claim 81, it is noted that an optimum administration regimens for IL-2 may be obtained by routine experimentation, absent a showing of criticality or unexpected results.
Regarding claim 82, Heemskerk teaches that the engineered PRAME TCR T cells can be used to treat relapsed or refractory myeloid neoplasms ([0392] and [0393]). Relapsed myeloid neoplasms reads on a recurrent cancer. By combining teachings of Mata and Heemskerk, one of ordinary skill in the art would have been motivated to treat relapsed myeloid neoplasms (e.g. myelodysplastic syndrome, also taught by Mata) with αβ T cells, and/or γδ T cells expressing R11P3D3KE, because the cancer is associated with expression of PRAME ([0393] of Heemskerk).
Regarding claim 85, Fig. 1 of Mata teaches activating T cells from a leukapheresis sample, transducing the activated T cells ex vivo with a lentiviral vector containing the genes encoding the TCR (also see [0048]). In addition, Mata teaches the method to produce autologous product ([0170]).
Regarding claims 86-88, Heemskerk teaches Lymphodepletion prior to T cell infusion with fludarabine 90 mg/m2 over 3 days with cyclophosphamide 750 mg/m2 ([0558-559]). Heemskerk teaches the lymphodepletion regimen is based on clinician assessment of their disease biology and comorbidities ([0553]).
Regarding claim 89, one ordinary skill in the art (e.g. a doctor) would be able to adjust dosage and application frequency to reach the claimed lymphodepletion regimen based on by routine experimentation, absent a showing of criticality or unexpected results.
Regarding claim 90, Mata teaches a method of preparing T cells for immunotherapy, including activating the T cells, transducing the activated T cells with the vector comprising the TCR, and expanding the transduced T cells ([0042], claims 1-5, and 27).
Regarding claim 91, Fig. 37 and [0216] of Mata teaches a T cell manufacturing process 370, which may include isolation of PBMC (371), in which PBMC may be used fresh or stored frozen till ready for use, or may be leukapheresis products, or may be used as starting materials for T cell manufacturing and selection of lymphocyte populations ( e.g., αβ TCR+ T cells, CD8+, CD4+, or both); thaw and rest lymphocytes overnight, e.g., about 16 hours or about 4-6 hours, (372), which may allow apoptotic cells to die off and restore T cell functionality (this step may not be necessary, if fresh materials are used); activation of lymphocytes (373), which may use anti-CD3 and anti-CD28 antibodies (soluble or surface bound, e.g., magnetic or biodegradable beads, antibodies immobilized on culture vessels); transduction with viral vectors containing sequences encoding recombinant proteins, e.g., CD8αβ and/or TCRαβ polypeptides (374), in which the viral vectors may be lentiviral vectors or retroviral vectors, or transfection may be performed by non-viral methods; and expansion of lymphocytes, harvest, and cryopreservation (375), which may be carried out in the presence of cytokine(s), e.g., IL-7 and IL-15, serum (ABS or FBS), and/or cryopreservation media.
Regarding claim 92, Heemskerk teaches that PRAME-specific T cell can recognize synovial sarcoma ([0006]), and PRAME-specific T cells can be used to treat synovial sarcoma ([0973]). By combining teachings of Mata and Heemskerk, one of ordinary skill in the art would have been motivated to treat synovial sarcoma with αβ T cells, and/or γδ T cells expressing R11P3D3KE, because the cancer is can be targeted by the T cells, thus, would be a good target for the engineered T cells.
Response to Arguments
For the 103 rejection, Applicant argues:
Mata, however, does not teach or suggest, at least, "wherein said PRAME-positive cancer is selected from a liposarcoma, a neuroblastoma, a myeloma, a synovial sarcoma, a bladder cancer, a hepatocellular cancer, a head and neck cancer, a fallopian tube cancer, primary peritoneal cavity cancer, advanced solid tumors, soft tissue sarcoma, a sarcoma, a myelodysplastic syndrome, a Hodgkin lymphoma, a non-Hodgkin lymphoma, a Hodgkin disease, a multiple myeloma, a metastatic solid tumors, a rhabdomyosarcoma, a myxoid round cell liposarcoma, an uterine corpus endometrial carcinoma, an uterine carcinosarcoma, a testicular germ cell tumor, a thymoma, a cervical squamous cell carcinoma, a cervical tumor, and a mesothelioma," recited in claim 76.
Heemskerk, however, does not teach or suggest what is missing in Mata.
Applicant’s arguments have been fully considered but they are not persuasive. Contrary to Applicant’s argument, Mata explicitly teaches that the engineered T cells can be used for treating various cancers, including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma ([0158]). Heemskerk teaches isolation of high affinity PRAME specific T cells that recognize the PRAME-derived peptide SLLQHLIGL (SEQ ID NO: 89) (SLL). Heemskerk teaches that the high affinity PRAME specific T cell clones showed high reactivity against a panel of PRAME positive tumor cell lines and against metastatic melanoma (reads on “a metastatic solid tumors”). In addition, Heemskerk teaches that PRAME-specific T cell can recognize synovial sarcoma ([0006]), and PRAME-specific T cells can be used to treat synovial sarcoma ([0973]). Thus, Mata and Heemskerk teaches the cancers recited by instant claim 76.
Thus, the rejection is maintained for the reasons of record.
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.
U.S. Patent No. 11,236,145 B2
Claims 76-82, and 85-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,236,145 B2 (hereinafter Pat. 145, Appl. 15/928,785, cited in IDS of 02/28/2023, of record) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
Claim 1 of Pat. 145 teaches an antigen recognizing construct comprising a T cell receptor (TCR) α chain comprising an α variable domain comprising CDR1α, CDR2α, and CDR3α of SEQ ID NO: 130, wherein the sequence of the α variable domain is at least 95% identical to SEQ ID NO: 130, and a TCR β chain comprising a β variable domain comprising CDR1β, CDR2β, and CDR3β of SEQ ID NO: 136, wherein the sequence of the β variable domain is at least 95% identical to SEQ ID NO: 136, wherein the antigen recognizing construct is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02.
Claim 18 of Pat. 145 teaches The antigen recognizing construct of claim 1, comprising the TCR α chain comprising the amino acid sequence SEQ ID NO: 132 and
the TCR β chain comprising the amino acid sequence of SEQ ID NO: 138. As shown below SEQ ID NO: 132 and SEQ ID NO: 138 comprise SEQ ID NO: 113 and SEQ ID NO: 119 of the instant application.
Alignment of SEQ ID NO: 132 of Pat. 145 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 138 of Pat. 145 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Pat. 145 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Pat. 145 teach a host cell comprising the TCR (claim 8), and wherein the host cell is a CD4-positive or CD8-positive T cell (claim 20).
The claims of Pat. 145 teach a pharmaceutical composition comprising the engineered TCR T cells (claim 21).
The claims of Pat. 145 teach a nucleic acid or two separate nucleic acids encoding the antigen recognizing construct according to claim 18 (claim 24).
Taken together, the claims of Pat. 145 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Pat. 145 do not teach treating PRAME-positive cancers as claimed with the TCR T cells, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Pat. 145. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 145, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL and HLA-2A by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Pat. 145 which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen bound by HLLA-A02 and Heemskerk teaches that SLLQHLIGL is expressed in various cancer (including sarcoma, synovial sarcoma) and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Pat. 145 for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-2A because these cancers would be targeted by the T cells expressing the PRAME-TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Pat. 145 would be able to induce immune response against cancers expressing SLLQHLGL and HLA-2A in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93 Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Pat. 145 based on the teachings of Mata and Heemskerk to a subject to treat a PRAME positive cancer with a reasonable expectation of success.
U.S. Patent No. 10,800,832 B2
Claims 76-82, and 85-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,800,832 B2 (hereinafter Pat. 832, Appl. 16/403,038, cited in IDS of 11/08/2022, of record) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
Claim 5 of the Pat. 832 teaches a method of treating a patient who has a PRAME positive cancer, comprising administering to the patient a population of transformed CD8+ T cells expressing at least one vector encoding a T cell receptor (TCR), wherein the TCR comprises a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 1, a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 2, a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 3,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 7, a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 8, and a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 9, wherein the TCR is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02, and wherein the cancer is selected from …, alveolar rhabdomyosarcoma (reads on “a sarcoma”), …, brain cancer, breast cancer, …, cancer of neck…liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, …, and urinary bladder cancer. As evidenced by Table 1 of the specification of Pat. 832, SEQ ID NO: 1-3 are CDRs 1-3 of R11P3D3 alpha chain, and SEQ ID NO: 7-9 are CDRs 1-3 of R11P3D3 beta chain. These CDRs are identical to the CDRs recited by the instant claim 76.
The claims of Pat. 832 teaches the method of claim 1, wherein the population of transformed cells are produced by a method comprising isolating a cell from a subject,
transforming the cell with at least one vector encoding the TCR to produce transformed cell, and expanding the transformed cell to produce the population of transformed cells (claim 2), wherein the subject is the patient (claim 3).
Taken together, the claims of Pat. 832 teach treating PRAME-positive cancers (such as sarcoma) with engineered TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Pat. 832 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells, or the full length alpha chain and beta chain.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Pat. 832. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 832, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Pat. 832 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Pat. 832 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Pat. 832 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Pat. 832 based on the teachings of Mata and Heemskerk to a subject to treat a PRAME positive cancers with a reasonable expectation of success.
U.S. Patent No. 11,111,286 B2
Claims 76-82, and 85-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,111,286 B2 (hereinafter Pat. 286, Appl. 16/731,139, cited in IDS of 11/08/2022, of record) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
It is noted that Pat. 286 and Pat. 145 share the same disclosure, thus, the same SEQ ID NO would have same sequences.
Claim 1 of Pat. 286 teaches a method of treating a patient who has a PRAME positive cancer, wherein the PRAME positive cancer is capable of presenting a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in the context of HLA-A*02 on the cell surface, comprising administering to the patient a population of transformed CD8+T cells expressing at least one vector encoding a T cell receptor (TCR), wherein the TCR comprises an α variable domain comprising CDR1α, CDR2α, and CDR3α of SEQ ID NO: 130, wherein the sequence of the α variable domain is at least 95% identical to SEQ ID NO:130, and a β variable domain comprising CDR1β, CDR2β, and CDR3β of SEQ ID NO: 136, wherein the sequence of the β variable domain is at least 95% identical to SEQ ID NO:136, wherein the TCR is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02, and wherein the cancer is selected from …,alveolar rhabdomyosarcoma (reads on “a sarcoma”),…Hodgkin lymphoma, …, non-Hodgkin lymphoma,… and urinary bladder cancer.
Claim 1 of Pat. 286 teaches that the TCR comprises an α chain comprising the amino acid sequence SEQ ID NO: 132 and a β chain comprising the amino acid sequence of SEQ ID NO: 138. As shown in above (Pat. 145 rejection), SEQ ID NO: 132 and SEQ ID NO: 138 comprise SEQ ID NO: 113 and SEQ ID NO: 119 of the instant application. Thus, the claims of Pat. 286 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
Taken together, the claims of Pat. 286 teach treating cancers with engineered TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Pat. 286 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Pat. 286. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 286, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Pat. 286 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Pat. 286 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Pat. 286 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Pat. 286 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
Application No. 17/553,017
Claims 76-82, and 85-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, 21, and 36-74 of copending Application No. 17/553,017 (hereinafter Appl. 017, of record) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
It is noted that Pat. 145 and Appl. 017 share the same disclosure, thus, the same SEQ ID NO would have same sequences.
The claims of Appl. 017 teach a method of manufacturing a therapeutic population of T cell receptor (TCR)-engineered T cells, the method comprising:
a. providing a plurality of T cells that express the TCR, the TCR comprising a TCRα chain and a TCRβ chain, and wherein the TCRα chain comprises: (i) a complementarity determining region (CDR)1α comprising the amino acid sequence of SEQ ID NO: 1, (ii) a CDR2α comprising the amino acid sequence of SEQ ID NO: 196, (iii) a CDR3α comprising the amino acid sequence of SEQ ID NO: 3; and the TCRβ chain comprises: (i) a CDR1β comprising the amino acid sequence of SEQ ID NO: 7, (ii) a CDR2β comprising the amino acid sequence of SEQ ID NO: 8; and (iii) a CDR3β comprising the amino acid sequence of SEQ ID NO: 9; and wherein the TCR is capable of binding to a peptide having an amino acid sequence comprising SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02, and
b. expanding the plurality of T cells into the therapeutic population of TCR-engineered T cells (claim 19).
The claims of Appl. 017 teach the method of claim 19, wherein the TCR has a TCR a chain as comprised in SEQ ID NO: 132 and a TCR p chain as comprised in SEQ ID NO: 138 (claim 41). As shown in above (Pat. 145 rejection), SEQ ID NO: 132 and SEQ ID NO: 138 comprise SEQ ID NO: 113 and SEQ ID NO: 119 of the instant application. Thus, the claims of Appl. 017 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 017 teach a therapeutic population of TCR-engineered T cells prepared by the methods of claim 19 (claim 67). Thus, the therapeutic population of TCR T cells would comprise the TCRα chain and the TCRβ chain as instantly claimed.
The claims of Appl. 017 teach wherein the T cells comprises CD8+ T cells and/or CD4+ T cells (claim 42).
Taken together, the claims of Appl. 017 teach a TCR T cell population, wherein the TCR comprises the alpha chain and beta chain as instantly claimed.
However, the claims of Appl. 017 teach treating PRAME-positive cancers with engineered TCR T cells expressing the alpha chain and beta chain as instantly claimed, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 017. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 017, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 017 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 017 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 017 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 017 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/505,361
Claims 76-82, and 85-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of copending Application No. 18/505,361 (hereinafter Appl. 361, of record) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
It is noted that Appl. 577 and Appl. 361 share the same disclosure, thus, the same SEQ ID NO would have same sequences.
The claims of Appl. 361 teach a method of treating a patient (or eliciting an immune response in a patient) who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface, comprising administering a population of T lymphocytes that express a T cell receptor (TCR) that binds a peptide comprising SLLQHLIGL (SEQ ID NO: 310) in a complex with a class I MHC molecule, …, wherein the metastasis or metastatic lesion originates from a cancer selected from the group consisting of …, sarcoma, …, synovial sarcoma, …, and extranodal T/NK-cell lymphomas (claims 1 and 2).
The claims of Appl. 361 teach the population of T lymphocyte is autologous or allogenic to the patient (claim 3).
The claims of Appl. 361 teach the TCR has an α chain variable domain comprising SEQ ID NO: 111, and a β chain variable domain comprising SEQ ID NO: 117 (claims 4 and 13).
As shown below SEQ ID NO: 111 and SEQ ID NO: 117 of Appl. 361 comprise SEQ ID NO: 111 and SEQ ID NO: 117 of the instant application.
Alignment of SEQ ID NO: 111 of Appl. 361 to SEQ ID NO: 111 of instant application:
Query Match 100.0%; Score 702; Length 132;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKP 132
||||||||||||
Db 121 RFGAGTRLTVKP 132
Alignment of SEQ ID NO: 117 of Appl. 361 to SEQ ID NO: 111 of instant application:
Query Match 100.0%; Score 710; Length 132;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVL 132
||||||||||||
Db 121 QYFGPGTRLTVL 132
Thus, the claims of Appl. 361 teach a TCR which reads on the TCR of instant claims 76 and 77.
The claims of Appl. 361 teach treating PRAME-positive cancers with the engineered T cells, as set forth above. However, the claims of Appl. 361 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells, or the full length alpha chain and beta chain.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 361. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 361, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 361 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 361 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 361 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 361 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/308,427
Claims 76-82, and 85-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-21 of copending Application No. 18/308,427 (hereinafter Appl. 427) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
The claims of Appl. 427 teach a T cell and/or NK cell transduced with a nucleic acid encoding (i) a polypeptide of SEQ ID NO: 311…..; or any combination of (i), (ii), (iii), and (iv) (claim 17); and a composition comprising the T cell and/or NK cell of claim 17 (claim 18); the composition further comprising an adjuvant such as IL-2 (claim 19).
The claims of Appl. 427 teach a T cell and/or NK cell of claim 17, comprising a nucleic acid comprising N1, N2, N3, N4, N5, L1, L2, L3, and L4, wherein N1 encodes a CD8β chain and is present or absent, …, N2 encodes a CD8α chain, …, N3 encodes a TCRβ chain, N4 encodes a TCRα chain, wherein N4 and N3 encode SEQ ID NO: 15 and 16, …, and N5 encodes at least one interleukin; …(claim 10). As shown below SEQ ID NO: 15 and SEQ ID NO: 16 comprise SEQ ID NO: 113 and SEQ ID NO: 119 (α chain and β chain of R11P3D3KE) of the instant application.
Alignment of SEQ ID NO: 15 of Appl. 427 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 16 of Appl. 427 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Appl. 427 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 427 teach a method of treating and/or eliciting an immune response in a patient who has cancer, comprising administering to the patient the composition of claim 18, wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, melanoma, liver cancer, breast cancer, uterine cancer, Merkel cell carcinoma, pancreatic cancer, gallbladder cancer, bile duct cancer, colorectal cancer, urinary bladder cancer, kidney cancer, leukemia, ovarian cancer, esophageal cancer, brain cancer, gastric cancer, and prostate cancer (claim 20).
The claims of Appl. 427 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed and methods of treating cancers with the T cells. However, the claims of Appl. 427 do not teach PRAME-positive cancers, or HLA-A02 positive, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 427. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 427, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 427 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 427 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 427 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 427 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/309,062
Claims 76-82, and 85-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-13, 17-19, and 21-25 of copending Application No. 18/309,062 (hereinafter Appl. 062) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
The claims of Appl. 062 teach a nucleic acid encoding a polypeptide comprising (i) a sequence at least about 95% identical to SEQ ID NO: 305; (ii) a sequence at least about 95% identical to SEQ ID NO: 307; or (iii) both (i) and (ii) (claim 1).
The claims of Appl. 062 teach the nucleic acid of claim 1, further comprising a nucleic acid sequence encoding at least one TCR polypeptide, at least one CD8 polypeptide, or at least one TCR polypeptide and at least one CD8 polypeptide (claim 3).
The claims of Appl. 062 teach the nucleic acid of claim 3, wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: 15 and 16, …, in particular wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: 15 and 16, …; wherein the CD8α chain is SEQ ID NO: 7, 258, 259, 262, or a variant thereof; wherein the CD8β chain is SEQ ID NO: 8, 9, 10, 11, 12, 13, or 14 (claim 5). As shown below SEQ ID NO: 15 and SEQ ID NO: 16 comprise SEQ ID NO: 113 and SEQ ID NO: 119 (α chain and β chain of R11P3D3KE) of the instant application.
Alignment of SEQ ID NO: 15 of Appl. 062 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 16 of Appl. 062 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Appl. 062 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 062 teach a T cell and/or natural killer (NK) cell transduced with the nucleic acid of claim 1 (claim 17); a composition comprising the T cell and/or natural killer (NK) cell of claim 17 (claim 18); the composition of claim 18 can further comprise an adjuvant such as IL-2 (claim 19).
The claims of Appl. 062 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Appl. 062 do not teach treating PRAME-positive cancers with the TCR T cells, or HLA-A02 positive, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 062. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 062, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 062 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 062 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 062 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 062 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/309,080
Claims 76-82, and 85-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/309,080 (hereinafter Appl. 080) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
The claims of Appl. 080 teach a nucleic acid encoding a polypeptide comprising SEQ ID NO: 311, 313, or 315 or a polypeptide at least about 95% identical to SEQ ID NO: 311, 313, or 315, said nucleic acid optionally comprising SEQ ID NO: 312, 314, or 316 or a sequence at least about 80%, at least about 85%, at least about 90%, at least about 95% identical to SEQ ID NO: 312, 314, or 316 (claim 1); the nucleic acid encoding a polypeptide comprising SEQ ID NO: 317, 321, 325, 327, 329, 331, or 333 or a polypeptide at least about 95% identical to SEQ ID NO: 317, 321, 325,327, 329, 331, or 333 (claim 3).
The claims of Appl. 080 teach the nucleic acid further comprising a nucleic acid encoding (a) at least one TCR polypeptide comprising an α chain and a β chain, (b) at least one CD8 polypeptide comprising (i) an α chain, (ii) a β chain, or (iii) both an α chain and a β chain, or (c) at least one TCR polypeptide comprising an α chain and a β chain and at least one CD8 polypeptide comprising (i) an α chain, (ii) a β chain, or (iii) both an α chain and a β chain (claim 7).
The claims of Appl. 080 teach the nucleic acid of claim 7 wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: 15 and 16, …; and wherein if present, the CD8β chain is …(claim 9). As shown below SEQ ID NO: 15 and SEQ ID NO: 16 comprise SEQ ID NO: 113 and SEQ ID NO: 119 (α chain and β chain of R11P3D3KE) of the instant application.
Alignment of SEQ ID NO: 15 of Appl. 080 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 16 of Appl. 080 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Appl. 080 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE. As set forth above, the TCR would read on the TCR of instant claims 76-78 and 93.
Taken together, the claims of Appl. 080 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Appl. 080 do not teach methods of treating PRAME-positive cancers with the T cells, or HLA-A02 positive, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 080. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 080, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 080 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 080 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 080 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 080 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 19/020,283
Claims 76-82, and 85-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of copending Application No. 19/020,283 (hereinafter Appl. 283) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023, of record) and Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023, of record).
The claims of Appl. 283 teach a nucleic acid comprising a nucleic acid sequence encoding: (i) a T-cell receptor (TCR) comprising a TCR α chain and a TCR β chain; and (ii) a CD8 polypeptide comprising an amino acid sequence which is at least 95% identical to SEQ ID NO: 5, 258, 259, 262, or a variant thereof (claim 1), a polypeptide encoded by the nucleic acid of claim 1 (claim 4).
The claims of Appl. 283 teach the TCR α chain and the TCR β chain can be SEQ ID NO: 71 and SEQ ID NO: 303 (claim 2). As evidenced by the Table 3 of the specification, the SEQ ID NO: 71 and SEQ ID NO: 303 are the α chain and the β chain of R11P3D3_KE. Thus, the TCR of Appl. 283 reads on the TCR of instant claims 76-78 and 93.
The claims of Appl. 283 teach a T cell transduced with the nucleic acid of claim 1 (claim 17), wherein the T cell is an αβ T cell and/or γδ T cell (claim 18).
The claims of Appl. 283 teach a T cell expressing the polypeptide of claim 4 (claim 21), a composition comprising the T cell of claim 21 (claim 23).
The claims of Appl. 283 teach a method of preparing T cells for immunotherapy comprising isolating T cells from a blood sample of a human subject, activating the isolated T cells, transducing the activated T cells with the nucleic acid of claim 1, and expanding the transduced T cells (claim 26).
The claims of Appl. 283 teach a method of treating a patient who has cancer, comprising administering to the patient the composition of claim 23, wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, melanoma, liver cancer, breast cancer, uterine cancer, Merkel cell carcinoma, pancreatic cancer, gallbladder cancer, bile duct cancer, colorectal cancer, urinary bladder cancer, kidney cancer, leukemia, ovarian cancer, esophageal cancer, brain cancer, gastric cancer, and prostate cancer (claim 27).
The claims of Appl. 283 teach as set forth above. However, the claims of Appl. 283 do not teach PRAME-positive cancers, or HLA-A02 positive, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a PRAME-positive cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma) with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 283. Heemskerk teaches methods for treating cancers (including recurrent cancers, synovial sarcoma) with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 283, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 283 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including sarcoma, myelodysplastic syndromes, Hodgkin lymphoma, and non-Hodgkin lymphoma …) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including sarcoma (such as synovial sarcoma), and the cancers (including recurrent cancers, synovial sarcoma) can be treated with TCR targeting PRAME-derived peptide SLLQHLIGL bound by HLA-A02and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 283 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) and HLA-A02 because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 283 and Mata would be able to induce immune response against cancers expressing SLLQHLGL and HLA-A02 in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 77-82, and 85-93, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 283 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
For the Double Patenting rejections, Applicant argues:
Applicant will determine whether to file a terminal disclaimer or not once claims are
otherwise found allowable.
Accordingly, withdrawal of the rejection is respectfully requested.
Applicant’s arguments have been fully considered but they are not persuasive. Because no Terminal Disclaimer has been filed, the rejections are still proper with the reasons of record. Thus, the rejections are maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHENG LU/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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