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 .
Priority
This application claims priority to provisional application 63/142,186, filed on 27 January 2021, and PCT application PCT/US2022/070199, filed on 14 January 2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The effective filing date is 27 January 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 20 July 2023, 28 February 2025, and 19 January 2026 are being considered by the examiner.
Status of Application, Amendments, and/or Claims
Claims 1-18 are the original claims filed on 20 July 2023. In the preliminary amendment of 20 July 2023, claims 3-6, 11, 13, and 16-18 are amended. Claims 1-18 are pending and the subject of this office action.
Drawings
The drawings are objected to because figures 9c, 10, and 11 are not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the term PERCOLL™, on page 27 line 21, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 is objected to because a number informalities are present. When describing the variable domains of the anti-CD19 antigen binding fragment the applicant seems to have incorrectly matched the sequences. The sequences provided, when referring to the “CD19VH”, are SEQ ID NOs: 1 and 2, but these sequences define light chain variable domains. The same informality is present when defining the light chain variable domain (i.e. the referenced sequences, SEQ ID NOs: 3 and 4, define heavy chains). Appropriate correction is required.
Claim Rejections - 35 USC § 103
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, 3-5, and 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10442867 (herein ‘867) in view of Ramos CA, et al. (2018) In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin's Lymphomas. Mol Ther. 2018 Dec 5;26(12):2727-2737 (herein Ramos).
In regard to claim 1, ‘867 teaches second-generation bi-specific anti-CD19/CD20 CAR T cells (abstract). One of the CAR polypeptides disclosed, SEQ ID NO:4, is comprised of a CD8 hinge/transmembrane domain, a 4-1BB co-stimulatory domain, a CD3 zeta domain, and a bi-specific anti-CD19/anti-CD20 extracellular domain comprising heavy chain and light chain amino acid sequences that share 100% sequence identity with those referenced in claim 1 of the instant application, as shown below:
CD19VL:
SEQ ID NO:1 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
Reference DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
************************************************************
SEQ ID NO:1 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT 107
Reference RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEIT 107
***********************************************
CD19VH:
SEQ ID NO:3 EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN 60
Reference EVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTYYN 60
************************************************************
SEQ ID NO:3 SALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS 120
Reference SALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTVSS 120
************************************************************
SEQ ID NO:3 AAA 123
Reference AAA 123
***
CD20VL:
SEQ ID NO:6 DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPAR 60
Reference DIVLTQSPAILSASPGEKVTMTCRASSSVNYMDWYQKKPGSSPKPWIYATSNLASGVPAR 60
************************************************************
SEQ ID NO:6 FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIK 106
Reference FSGSGSGTSYSLTISRVEAEDAATYYCQQWSFNPPTFGGGTKLEIK 106
**********************************************
CD20VH:
SEQ ID NO:5 EVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSY 60
Reference EVQLQQSGAELVKPGASVKMSCKASGYTFTSYNMHWVKQTPGQGLEWIGAIYPGNGDTSY 60
************************************************************
SEQ ID NO:5 NQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTV 120
Reference NQKFKGKATLTADKSSSTAYMQLSSLTSEDSADYYCARSNYYGSSYWFFDVWGAGTTVTV 120
************************************************************
SEQ ID NO:5 SS 122
Reference SS 122
**
In addition to antigen binding component of the extracellular portion of the disclosed CAR element sharing 100% sequence within the variable domains, the extracellular portion of the receptor also shares a formula with one of the embodiments disclosed in claim 1 of the instant application: SP-CD19VL-CD19VH-CD20VH-CD20VL—CD8 Hinge (SEQ ID NO:4 and figure 1a). It should also be noted that ‘867 also discloses additional formulas that match with the extracellular portion of the receptor, as well as several embodiments that fully encompass the certain formulas listed in instant claim 1 (e.g. SP-CD19VL-CD19HL-CD20VH-CD20-VL-CD8-CD28-CD3z)(figure 1a, column 7 lines 37-40, column 8 lines 36-42). Additionally, ‘867 teaches that the CAR disclosed may include additional intracellular co-stimulatory domains, with CD28 being listed as an example (claims 5 and 6).
‘867 does not specifically teach a third-generation anti-CD19/CD20 CAR polypeptide that contains both CD28 and 4-1BB co-stimulatory domains, although the claim language of the referenced patent does encompass the limitations established in the instant claim. Ramos teaches this deficiency.
Ramos teaches third-generation anti-CD19 CAR T cell comprising co-stimulatory domains from CD28 and 4-1BB (abstract). Ramos et al show that the third-generation CAR T cells showed superior expansion and longer persistence in a phase 1 clinical trial, NCT01853631, compared to second-generation CAR T cells containing only a single co-stimulatory domain (Results: CD19.CART Expansion and Persistence). In patients with relapsed or refractory non-Hodgkin’s lymphoma, patients receiving the third-generation CAR T cells showed higher peak CAR T expansion, up to 40-fold higher, than that observed for second-generation cohort. In addition to superior expansion in diseased patients, the third-generation CAR T cells also showed superior persistence, as measured by quantified transgene copy number, six weeks post-infusion. In the abstract section the authors note that “CD19.CARTs combining 4-1BB with CD28 produce superior CART expansion and may be of particular value when treating low disease burden in patients whose normal B cells are depleted by prior therapy.”
It would have been obvious to one skilled in the art to combine the teachings of ‘867 (bi-specific CD19/CD20 CAR T cells) with the CAR T polypeptide design incorporating both CD28 and 4-1BB co-stimulatory domains taught by Ramos. One of ordinary skill in the art at the time of filing would have been motivated to incorporate the dual co-stimulatory domain design with the recognized benefit of generating CAR T cells possessing superior expansion and persistence compared to CAR T cells transduced with CAR T elements only utilizing a single co-stimulatory domain, as taught by Ramos. Furthermore, by combining these pre-existing elements, the instant application discloses a claimed invention that behaves in a predictable manner, based on the prior art describing each element individually.
In regard to claim 3, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches a CAR T polypeptide amino acid sequence, SEQ ID NO: 4, in which the amino acid sequence of the 4-1BB domain shares 100% sequence identity with the sequence referenced in claim 3 of the instant application, SEQ ID NO: 8, as shown below:
SEQ ID NO: 8 RGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 41
Reference RGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 41
*****************************************
In regard to claim 4, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches a CAR T polypeptide amino acid sequence, SEQ ID NO: 4, in which the amino acid sequence of the CD8 hinge shares 100% sequence identity with the sequence referenced in claim 4 of the instant application, SEQ ID NO: 9, as shown below:
SEQ ID NO: 9 TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLL 60
Reference TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLL 60
************************************************************
SEQ ID NO: 9 LSLVITLYC 69
Reference LSLVITLYC 69
*********
In regard to claim 5, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches the use of the Whitlow linker loop as it is within the CAR polypeptide disclosed in SEQ ID NO:4, and shown below:
Instant GSTSGSGKPGSGEGSTKG 18
Reference GSTSGSGKPGSGEGSTKG 18
******************
In regard to claims 11 and 12, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches that the CAR element may be transduced into T cells, including but not limited to, CD4+/CD8+ double positive T cells, CD4+ helper T cells, e.g., Thl and Th2 cells, CD8+ T cells (e.g., cytotoxic T cells), tumor infiltrating cells, memory T cells, memory stem cells, i.e. Tscm, naive T cells, and the like (column 39 lines 37-55). It is also taught that the CAR element may be expressed in suitable non-T cells, such as those with immune-effector function (i.e. NK cells and T-like cells) (column 39 lines 52-55).
In regard to claims 13 and 16, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches a method for using the disclosed CAR T cells for the treatment of various B cell malignancies, such as acute lymphocytic leukemia, acute myeloid leukemia, and hairy cell leukemia (column 40 lines 66- column 41 lines 23).
In regard to claims 14 and 15, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
The data used in the study presented by Ramos et al was generated during a clinical trial, NCT01853631, in which a subset of the patients was allowed to receive anti-PD-1 immunotherapy in combination with CAR T adoptive therapy.
In regard to claims 17 and 18, ‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches a method of treating B cell malignancies in which the CAR T cells are either autologous or allogenic in nature (column 40 lines 41-53).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10442867 (herein ‘867) in view of a Ramos CA, et al. (2018) In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin's Lymphomas. Mol Ther. 2018 Dec 5;26(12):2727-2737 (herein Ramos) with US20140322212 A1 (herein Brogdon) providing additional evidentiary value.
‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1.
‘867 teaches a CAR T polypeptide amino acid sequence, SEQ ID NO: 4, in which the amino acid sequence of the CD3 zeta domain shares 99.11% sequence identity with the sequence referenced in claim 2 of the instant application, SEQ ID NO: 7, as shown below:
Instant RVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
Reference RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
*************:**********************************************
Instant ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
Reference ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
****************************************************
Although the two sequences do not share complete sequence identity, they are taught to be functional equivalents, as disclosed by Brogdon, in which the two variants are shown to be interchangeable ([0014], SEQ ID Nos: 7 and 98). For further guidance on the matter see MPEP 2144.06.
Claims 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 10442867 (herein ‘867) in view of a Ramos CA, et al. (2018) In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin's Lymphomas. Mol Ther. 2018 Dec 5;26(12):2727-2737 (herein Ramos), Tai X, et al. (2005) CD28 co-stimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat Immunol. 2005 Feb;6(2):152-62 (herein Tai), and WO 2019/010383 (herein Davila), which is associated U.S. Patent No. 12065474.
‘867 and Ramos teach a CAR polypeptide comprising a bi-specific CD19/CD20 antigen binding domain, a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3z stimulatory domain, as discussed above for the 103 rejection of claim 1. ‘867 and Ramos do not teach a CAR polypeptide with conservative null mutations in PRRP and YMNM subdomains of the CD28 co-stimulatory domain. Davila and Tai teach these deficiencies.
Davila teaches CAR polypeptides comprising mutation in the CD28 co-stimulatory domain (abstract). The mutant CD28 co-stimulatory domains comprise mutations that perturb either a single or multiple kinase binding motifs (page 42 line 15 – page 43 line 30). Davila teaches three kinase binding motifs that are the targets of null mutations (all amino acid substituted to alanine), YMNM, PRRP, and PYAP (page 3 lines 29-34 and figure 2a). In an example embodiment, a second-generation anti-CD19 CAR T cell comprising a CD28 double null mutant, null YMNM and null PRRP motifs (relevant to instant claims 6 and 7), outperformed a comparable CAR T cell population transduced with a CAR element comprised of the wild-type CD28 cytoplasmic domain in an in vivo experiment measuring survival time of mice with Eu-ALL tumors (page 44 lines 15-17 and figure 10). Davila effectively demonstrates that by disrupting two out of three kinase binding sites within the cytoplasmic tail of the CD28 co-stimulatory domain, in the context of a CAR element, one is able to produce CAR T cells with enhanced in vivo efficacy. However, Davila does not teach the use of conservative amino acid substitutions in the null mutations. These are taught by Tai.
Tai teaches CD28 structural motifs required for efficient Treg cell generation (Results: CD28 motifs required for Treg cell generation). Tai et al systematically mutate the three kinase binding domains found within the cytosolic tail of CD28 to identify the effects that each motif has on Treg generation. It is taught that the PYAP motif is essential for Treg generation and Lck binding (figure 2). The null mutations used to perform this experiment were conservative mutations, relative to those taught by Davila, which is relevant to instant claims 8-10 ((YMNM[Wingdings font/0xE0]FMNM), (PRRP[Wingdings font/0xE0]ARRA), and (PYAP[Wingdings font/0xE0]AYAA)) (figure 2).
It would have been obvious to one skilled in the art to combine the teachings of ‘867 and Ramos (an anti-CD19/CD20 bi-specific CAR T cell with a CD8 hinge, 4-1BB and CD28 co-stimulatory domains, and a CD3 zeta stimulatory domain) with a mutated CD28 cytosolic tail cells taught by Davila and Tai. One of ordinary skill in the art at the time of filing would have been motivated to incorporate the mutated CD28 domain, with the recognized benefit of enhanced survival duration and reduced exhaustion, as taught by Davila, into the third-generation anti-CD19/CD20 CAR T cell taught by ‘867 and Ramos. One would have been motivated to use the conservative kinase binding motif mutations taught by Tai, due to the decreased likelihood of unintended interactions or structural perturbations that may have resulted from non-conservative substitutions, which would have been obvious to one skilled in the art. Furthermore, by combining these pre-existing elements, the instant application discloses a claimed invention that behaves in a predictable manner, based on the prior art describing each element individually.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 6-10, and 11-15 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1 and 10-16 of U.S. Patent No. 12065474 (herein ‘474) in view of U.S. Patent No. 10442867 (herein ‘867), Ramos CA, et al. (2018) In Vivo Fate and Activity of Second- versus Third-Generation CD19-Specific CAR-T Cells in B Cell Non-Hodgkin's Lymphomas. Mol Ther. 2018 Dec 5;26(12):2727-2737 (herein Ramos), Tai X, et al. (2005) CD28 co-stimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat Immunol. 2005 Feb;6(2):152-62 (herein Tai), and WO 2019/010383 (herein Davila), which is associated U.S. Patent No. 12065474
‘474, claim 1, describes a CAR polypeptide, comprising a CD28 co-stimulatory domain, wherein the cytoplasmic tail has been mutated to contain at least one null kinase binding motif, and in which the PYAP motif is wild-type, which is relevant to instant claims 1, 6, and 7.
However, ‘474 does not indicate an anti-CD19/CD20 bispecific CAR polypeptide comprising an anti-CD19/CD20 binding domain, a CD8 hinge, CD28 and 4-1BB co-stimulatory domains, and a CD3 zeta domain. Regarding the bi-specific anti-CD19/CD20 extracellular domain, ‘867 teaches the bi-specific domain for the treatment of B cell malignancies (abstract, column 40 lines 41-53). Further teaching regarding an anti-CD19 CAR polypeptide comprising both CD28 and 4-1BB co-stimulatory domain is provided by Ramos, who teaches that third-generation CAR T cells showed superior expansion and longer persistence in a phase 1 clinical trial, NCT01853631, compared to second-generation CAR T cells containing similar domains (Results: CD19.CART Expansion and Persistence), and thus provides the rationale/motivation for combining the teachings of ‘867 and Ramos. One of ordinary skill in the art to further combine the teachings of ‘867 and Ramos with the mutated CD28 cytoplasmic tail of ‘474 via the conservative mutations taught by Tai, as discussed for the 103 rejection of claims 6-10. There would have been reasonable expectation of success based on the prior art describing each element individually.
In regard to instant claims 11-16, ‘474, ‘867, Tai, and Ramos teaches an anti-CD19/CD20 bispecific CAR polypeptide, as discussed above for instant claims 1 and 6-10.
Claims 10-14 of ‘474 teach immune effector cells comprising a vector that allows for the expression of the aforementioned CAR polypeptide (claims 10-12 of ‘474 and relevant to instant claims 11 and 12), which are further taught to be used in a method for providing anti-tumor immunity (claim 13 and 14 of ‘474 and relevant to instant claim 13). Claims 15 and 16 of ‘474 also teaches that the method for providing anti-tumor immunity may be combined with a checkpoint inhibitor, such inhibitors may target PD-1, PD-L1, or CTLA-4, which are relevant to instant claims 14 and 16.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW CURRAN METCALF whose telephone number is (571)272-5520. The examiner can normally be reached 7:30AM-5:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/MATTHEW CURRAN METCALF/ Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647