DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-35, 37, 39-40, 45, and 47 are cancelled. Claims 36, 38, 41-44, 46, and 48-59 as filed on 23 December 2025 are pending and under examination.
Terminal Disclaimer
The terminal disclaimer filed on 23 December 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent 11,352,434 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Rejections Withdrawn
Rejection of claims 37, 39, 45, and 47 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 103 are withdrawn with cancellation of claims.
Rejection of claims 36-57 under Double Patenting is withdrawn with approved Terminal Disclaimer.
Rejections Maintained – Amendment of Rejection Necessitated by Applicant Amendment of Claims
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 36, 46, 49, and 51-56 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Finer (US20150329640) (IDS), as evidenced by Finer ‘671 (WO2014099671) (IDS).
Regarding claims 36, 46, 49, and 54, Finer teaches a method of treating B cell malignancies using anti-CD37 CAR wherein the CAR comprises an anti-CD37 scFv (i.e., an extracellular domain comprising a CD37 binding sequence that is an antibody reagent) linked to a transmembrane domain linked to a CD3z T cell intracellular signaling domain ([0009]-[0010] and [0049], abstract, and claim 24). Finer teaches the method comprising treatment of CLL ([0004]). Finer further teaches that their CD37 binding CARs bind and kill CD37 expressing target cells ([0008]).
Regarding claims 51-55, Finer teaches a CD8 transmembrane domain ([0010], [0073]) and a CD28 transmembrane domain and 4-1BB co-stimulatory domain. Finer teaches in [0010], [0076]-[0077], and shown in SEQ ID NOS: 1 and 3 and in Figures 4 and 6 of Finer, the CAR may also optionally comprise a co-stimulatory domain that is a 4-1BB co-stimulatory domain. As evidenced by Table 5 of WO2014099671, nucleotides 5082-5207 of pCAR CD37-28BZ vector shown in Figure 6 and set forth in SEQ ID NO: 3 encodes the 4-1BB intracellular domain. The encoded sequence is either identical to the sequence of SEQ ID NO: 13 or 19 or to a variant thereof.
Regarding claim 56, Finer teaches the treatment of a human subject ([0142]).
Applicant Arguments
Applicant argues the amendment of the claims to require a CD37+ cancer that is CLL, Burkitt’s Lymphoma, AML, mantle cell lymphoma, or T-cell lymphoma.
Response to Arguments
Applicant's arguments filed 23 December 2025 have been fully considered but they are not persuasive.
As previously stated and repeated in the current rejection Finer teaches a method of treating CLL ([0004]) using anti-CD37 CARs. Finer further teaches that their CD37 binding CARs bind and kill CD37 expressing target cells ([0008]). This would be the treatment of CLL that expresses CD37.
Rejections Maintained – Amendment of Rejection Necessitated by Applicant Amendment of Claims
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 36, 41-43, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Finer (US20150329640) (IDS), as evidenced by Finer ‘671 (WO2014099671) (IDS), and Tan (US20090274692) (IDS).
The teachings of Finer and Finer ‘671 from the previous art rejections are incorporated here in full.
Finer teaches the treatment of B cell malignancies with CD37 binding CARs (Abstract [0004]).
Finer further teaches Burkitt’s lymphoma and CLL are CD37+ ([0043]) and B cell NHL ([0004]).
Finer at [0043] reviews the role of CD37 targeting in treating B cell malignancies, including prior studies with a CD37 IgG1-like antibody. Finer also teaches that the CD37-specific CAR provides an advantage over prior approaches to targeting CD37-expressing cells because it kills those cells by an additional mechanism [0044]-[0045]. Further, Finer teaches that CD37-based killing, at least on B cells tumors, is more efficient than that mediated by CAR recognizing alternate ligands on the same tumor target, such as CD20 and CD19 [0045].
Finer does not explicitly teach specifically the use of CD37 binding CARs used in the treatment of Burkitt’s lymphoma, CML, acute myeloid leukemia, and mantle cell lymphoma. Finer also does not teach treating cancer in a subject who is non-responsive to anti-CD19 and/or anti-CD20 therapy.
These deficiencies are filled by Tan.
Tan teaches CD37 specific CARs that are used in the treatment of B cell malignancies (abstract). Tan teaches the treatment of Burkitt’s lymphoma, CLL, ALL, acute myeloid leukemia, and mantle cell lymphoma as CD37+ cancer ([0133]-0135]).
Tan teaches using a humanized anti-CD37-small modular immunopharmaceutical (SMIP) molecules for treating B-cell related autoimmune, inflammatory, and hyperproliferative disorders. See entire document, e.g., Abstract. The anti-CD37 antibody that Tan uses is a humanized version of the G28-1 antibody that is also used by Finer. E.g., Figure 1, [0057].
It would have been obvious at the time the application was filed to use the CAR of Finer in the patient populations of Burkitt’s lymphoma, CLL, acute myeloid leukemia, and mantle cell lymphoma or a subject who is non-responsive to anti-CD19 and/or anti-CD20 therapy as taught by Tan. In view of Finer’s teachings regarding the enhanced killing efficiency of the anti-CD37 CAR therapy compared to targeting CD20 or CD19 on B cell tumors, the ordinary artisan prior to the effective filing date would also have found it obvious to apply the CD37 CAR therapy to patients that were non-responsive to anti-CD20 and/or anti-CD19 therapy, each of which were already applied clinically to treat various tumors. Accordingly, the ordinary artisan would have been motivated to actively select those patients that were non-responsive to anti-CD19 and/or anti-CD20 therapy for treatment with the anti-CD37 CAR T cells of Finer, as required by the method of claim 30, because non-responsive patients were particularly in need of an alternative therapy.
In addition, in view of the teachings of Finer and Tan, the ordinary artisan before the effective filing date of the claimed invention would have found it obvious to utilize the CD37-specific CAR of Finer to not only treat various cancers such as those taught by Tan. Finer teaches that the anti-CD37 CAR should be advantageous over other anti-CD37 therapies because the anti-CD37 CAR can eliminate CD37-expressing cells by more than one mechanism. Accordingly, the ordinary artisan prior to the effective filing date would have found it obvious to extend the therapies taught by Finer to also included treating the particular lymphomas and leukemias taught by Tan.
Applicant Arguments
Applicant argues the combination of the anti-CD37 CAR T cell of Finer in the patient populations of Tan would be unpredictable arguing the anti-CD37 CAR T of Finer would target CD37 expressing cells and induce T cell fratricide.
Applicant argues Finer only exemplifies anti-CD37 CAR constructs and no generation or testing of anti-CD37 CAR T cells. Applicant argues Tan is silent with respect to CAR T cells or the use of anti-CD37 antibodies with CAR T cells.
Applicant argues Tan teaches a decrease in cytokine levels after administration of CD37-binding molecules to patients with rheumatoid arthritis which may be due to reduced B cell number or decreased activated T cells, suggesting that targeting CD37 can have adverse effects on T cell function and thus not work in cancer killing. Applicant argues Finer and Tan do not provide suggestion that anti-CD37 CAR T cells would not commit T cell fratricide, which would be expected by the person of ordinary skill, making them unsuitable for treatment of T-cell lymphoma, CLL, Burkitt’s lymphoma, mantle cell lymphoma, AML, of CML.
Applicant argues the anti-CD37 CAR T cells of the present application did not cause T cell fratricide, which would not have been predictable based on the state of the art at the time of the filing. Applicant points to mouse engrafted Jeko-1 cancer cells.
Response to Arguments
Applicant's arguments filed 23 December 2025 have been fully considered but they are not persuasive.
Finer teaches anti-CD37 CAR T cells for use in a method of treating B cell lymphomas. The inventions of Finer would be CD37-specific binding molecules. Finer explicitly teaches the CAR T cells of the invention in context of what is known in the art to one of ordinary skill and recites:
CAR T cells are able to redirect immune effector cell specificity, thereby triggering proliferation, cytokine production, phagocytosis or production of molecules that can mediate cell death of the target antigen expressing cell in a major histocompatibility (MHC) independent manner, exploiting the cell specific targeting abilities of monoclonal antibodies, soluble ligands or cell specific co-receptors ([0040]). Although scFv-based CARs engineered to contain a signaling domain from CD3 or FcRγ have been shown to deliver a potent signal for T cell activation and effector function, they are not sufficient to elicit signals that promote T cell survival and expansion in the absence of a concomitant co-stimulatory signal. A new generation of CARs containing a binding domain, a hinge, a transmembrane and the signaling domain derived from CD3ζ or FcRγ together with one or more co-stimulatory signaling domains (e.g., intracellular co-stimulatory domains derived from CD28, CD137, CD134 and CD278) has been shown to more effectively direct antitumor activity as well as increased cytokine secretion, lytic activity, survival and proliferation in CAR expressing T cells in vitro, in animal models and cancer patients ([0041]). According to the present invention, CARs expressed on immune effector cells initiate target cell killing following binding to specific ligand expressed on the target cell. Such CAR-mediated death occurs because CAR ligation triggers immune effector cell activation, resulting in induction of effector cell signaling pathways (e.g. granule exocytosis, up-regulation of FasL and secretion of pro-inflammatory cytokines) that drive target cell apoptosis ([0044]).
One of skill in the art as shown by Finer would be taught to use the CAR T cells of Finer for use in targeting cancer cells where CD37 is expressed on their surface to target by immune effector cell activation-dependent pathways utilized by other CARs, but also by direct CD37 ligation-mediated apoptosis. Since CD37 is expressed on B cell tumors, tumor killing mediated by CD37 CAR is more efficient than that mediated by CAR recognizing alternative ligands on the same tumor target ([0045]).
Tan teaches CD37-specific binding molecules as SMIP proteins and antibodies for use in treatment of patients (abstract).
Finer teaches the use of their CAR T cells in method of treatment in cancer where the target cells express CD37. Tan teaches CD37-specific binding molecules, including antibodies, for use in treatment of cancer.
The deficiencies of Tan support the use of Finer’s CAR T cells in the method of treatment as Tan does not teach CAR T cells and as taught by Finer CAR T cells are an improved method of targeting antigens expressed on cancer cells for use in methods of treatment.
Finer and Tan do not teach on T cell fratricide, but both teach the use of CD37 binding molecules for use in treating cancer with Finer teaching the use of the CAR T cells in a method of treating cancer wherein the cancer cells express CD37. The lack of teaching of fratricide is a lack of teaching away not evidence that Finer and Tan are teaching away from the method of the claims.
Regarding applicant’s claim of unexpected results in Example 2. Applicant has only shown effective method of treatment with the anti-CD37 CAR-37 which comprises a VH and VL of SEQ ID NO: 4 and 2, a CD8 transmembrane domain, a 4-1BB co-stimulatory domain and CD3 zeta intracellular signaling domain. The applicant has not shown results for the CAR T cells of rejected by the art which has no defined VH and VL, and allows for variation in all other domains of the CAR. The applicant has not shown surprising results commensurate with the scope of the claims.
Claims 36, 44, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Finer (US20150329640) (IDS), as evidenced by Finer ‘671 (WO2014099671) (IDS), Stern (US 20150283142 A1) (IDS), and Schwartz-Albiez et. al. (J Immunol) 140(3):905-914 (1988) (Of Record).
The teachings of Finer and Finer ‘671 from the previous art rejections are incorporated here in full.
Finer teaches the treatment of B cell malignancies with CD37 binding CARs (Abstract [0004]).
Finer further teaches Burkitt’s lymphoma and CLL are CD37+ ([0043]) and B cell NHL ([0004]).
Finer does not teach the treatment of PTCL.
This deficiency is filled by Stern and Schwartz-Albiez.
Stern teaches a method of treating cancers including PTCL with an anti-CD37 antibody (claims 1, 7, 10-11, and 54-55).
Schwartz-Albiez teaches CD37 expression including on T cells (Table 1).
It would have been obvious at the time the application was filed to substitute the patient population being treated of a CD37+ B cell malignancies taught by Finer with the PTCL patient population of Stern. Finer teaches an anti-CD37 CAR used in treating CD37+ cancers and Stern and Schwartz-Albiez teach T cells as CD37+ with Stern teaching the use of an anti-CD37 antibody in the treatment of PTCL. One of ordinary skill in the art would have been motivated to use the successful method of treatment taught by Finer in additional patient populations as it would have potential utility in saving patient lives and provide financial gain in its method of treatment. There would have been a reasonable expectation of success as Finer teaches use in CD37+ malignancies, and Stern teaches the method of targeting CD37 in PTCL patients.
Applicant Arguments
Applicant argues the specific cancers of the claims are not taught as treated using a CAR T cell that binds CD37. Applicant repeats the argument previously responded to in the previous 103 rejection regarding T cell fratricide.
Applicant argues Stern does not teach CAR T cells or the use of anti-CD37 antibodies with CAR T cells.
Applicant states Schwartz-Albiez teaches structure and presence of CD37.
Applicant argues the unexpected results of the CAR T cells of the instant application did not result in T fratricide.
Response to Arguments
Applicant's arguments filed 23 December 2025 have been fully considered but they are not persuasive.
Stern is not relied upon to teach CAR T cells or the use of anti-CD37 antibodies with CAR T cells in a method of treatment. The art rejection is the substitution of the patient population of the method of treatment of Finer with the patient populations of Stern. Stern teaches the use of anti-CD37 antibodies in a method of treating the patient population having PTCL. Finer teaches the use of CAR T cells for use in a method of treating cancer that expresses CD37 and explicitly teaches the superiority of CAR T cells for use a method of treatment over previous methods which includes antibodies that bind the antigens of the CAR T cells. One of skill in the art would have been motivated by the superiority of CAR T cells in populations previously treated with antibodies as taught by Stern.
Regarding applicant’s claim of unexpected results in Example 2. Applicant has only shown effective method of treatment with the anti-CD37 CAR-37 which comprises a VH and VL of SEQ ID NO: 4 and 2, a CD8 transmembrane domain, a 4-1BB co-stimulatory domain and CD3 zeta intracellular signaling domain. The applicant has not shown results for the CAR T cells of rejected by the art which has no defined VH and VL, and allows for variation in all other domains of the CAR. The applicant has not shown surprising results commensurate with the scope of the claims.
Allowable Subject Matter
Claims 50, 57, and 59 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643