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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 24, 2025 has been entered.
Application Status
The amended claims filed September 24, 2025 are acknowledged. Claims 25, 29-31, 36, 40-47, and 52-55 are pending. Claims 29, 31, 43, and 52-53 are amended. Claim 25 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 29-31, 36, 40-47, and 52-55 are under examination herein.
NEW OBJECTIONS AND REJECTIONS NECESSITATED BY CLAIM AMENDMENT
Claim Objections
Claim 53 is objected to because of the following informalities: The claim does not end in a period. As set forth in MPEP § 608.01(m), each claim should end with a period.
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.
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.
Claims 29-31, 36, 40-47, and 52-55 are rejected under 35 U.S.C. 103 as being unpatentable over June (US 2017/0209492 A1; earliest priority date: July 31, 2014), optionally further in view of Lokhorst (The New England Journal of Medicine (2015) 373(13): 1207-1219) and Krejcik (Blood (2016) 128(3): 384-394).
June discloses optimized CD4+ and CD8+ CAR-T cells and methods of use thereof in treating cancer (e.g., Abstract; ¶ 0003). Relevant to claims 29, 40, and 53, June discloses a method of treating cancer in subject in need thereof, comprising administering to the subject a CD4+ CAR-T cell (CARCD4+) and a CD8+ CAR-T cell (CARCD8+), wherein the CD4+ CAR-T cell is a Th17 polarized cell1 that produces IL-17A and IFN-γ, i.e., hybrid Th1/Th17 cells, and wherein the CARCD4+ comprises an antibody variable domain, an scFv, or an antigen-binding fragment thereof (e.g., ¶ 0047-0129; claims 14, 31-32, 45). June discloses that the antigen-binding domain of the CARs may bind to a tumor antigen such as CD38 (e.g., ¶ 0370-0381). Relevant to claim 36, the cancer to be treated may be a lung cancer, or melanoma, or prostate cancer, or multiple myeloma (e.g., ¶ 0370-0373, 0748-0752).
Regarding claims 30-31, which are both in the format of a product-by-process claim (while the claims are drawn to methods of treating cancer by administering a product, these claims recite how the product that is administered is made, the claims are not drawn to a method of making the product per se), MPEP § 2113 (I) sets forth: "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). June states that for polarization of Th17 cells, CD4+ cells were stimulated with anti-CD3 and anti-ICOS antibodies and cultured in the presence of IL-1β, IL-6, IL-23, and neutralizing anti-IL-4 and IFN-γ antibodies, with fetal calf serum containing endogenous TGF-β (e.g., ¶ 0933) which produces hybrid Th1/Th17 cells indistinguishable from those claimed2.
Relevant to claims 41-45, June teaches that an agent which enhances the activity of the CAR-expressing CD4+ or CD8+ T cells of the invention may be further administered, e.g., the anti-PD-1 antibody nivolumab or an anti-CTLA-4 antibody such as ipilimumab or tremelimumab (e.g., ¶ 0828-0831). Relevant to claims 46-47, June teaches that a lymphodepleting chemotherapy may be administered before, concurrently with, or after administration of the CAR-T cells of the invention (e.g., ¶ 0825).
Relevant to claims 53 and 55, June states that T cells used in the methods of the invention can be selected for their expression of one or more of IFN-γ, IL-17A, and granzyme (GZMB) (e.g., ¶ 0619). Although June does not expressly teach that the Th17 polarized cells express the markers set forth in claims 52 and 54-55, it is noted that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP § 2112.01. Accordingly, supported by the reasoning of the Federal Circuit in Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342,1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999), it is submitted that the claiming of a previously uncharacterized property of a prior art composition as set forth in claims 52 and 54-55 does not render embodiments present in the old composition patentably new to the discoverer. In this case, the CAR-expressing Th17 polarized cells disclosed by June meet the structural requirements of the independent claim and thus necessarily would have the instantly claimed properties absent a showing otherwise.
While June does not expressly describe administering a CARCD4+ Th17 polarized cell in combination with a stand-alone anti-CD38 antibody, it would have been obvious to administer the CAR-expressing CD4+ T cells and CD8+ T cells of the invention of June in combination with a stand-alone anti-CD38 antibody. June expressly teaches that the CAR-expressing CD4+ T cells and CD8+ T cells of the invention may be administered with at least one additional therapeutic agent, including an antibody, so as to make the treatment method more effective (e.g., ¶ 0772-0776). June further recites that the CAR-expressing T cells administered in the methods of the invention may be co-administered with a molecule that decreases the Treg cell population (e.g., ¶ 0787). One of ordinary skill in the art would have been motivated to co-administer an anti-CD38 antibody, for example, in the treatment of multiple myeloma (a cancer sought to be treated by June), because treatment with the anti-CD38 antibody daratumumab “had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory multiple myeloma” (as taught by Lokhorst, e.g., at Abstract) and because daratumumab depletes CD38+ Tregs (as taught by Krejcik, e.g., at Abstract; Results; Figure 3). There would have been a reasonable expectation of success because, as noted by Lokhorst, CD38 is uniformly overexpressed in multiple myeloma (e.g., Abstract; Introduction).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
1 As evidenced by the instant specification (¶ 0056), “the term ‘hybrid Th1/Th17’ or ‘Th1/17’ refers to a population of T cells which co-express IFNγ and IL17”.
2 It is suggested that if Applicant desires the steps to be active steps in the process to amend claim 30 to recite, “The method of claim 29, further comprising before the administration step (a) obtaining a starting population of T cells comprising CD4+ and CD8+ T cells; and (b) culturing the starting population of T cells in the presence of recombinant IL6, IL1IL23, TGFP, IL-12, and anti-IL-4, thereby differentiating the starting population of T cells to hybrid Th1/Thl7 and/or Tc1/Tcl7 cells” and amend claim 31 to recite, “The method of claim 29, further comprising before the administration step (a) obtaining a starting population of T cells comprising CD4+ and CD8+ T cells; and (b) culturing the starting population of T cells in the presence of recombinant IL6, IL1IL23, TGFP, IL-12, anti-IL-4 and anti-CD38, thereby differentiating the starting population of T cells to hybrid Th1/Thl7 and/or Tc1/Tcl7 cells with reduced expression of CD38”.
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