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
Applicant’s election without traverse of Group I, claims 1, 2, 6, and 7, in the reply filed on 01/21/2026 is acknowledged.
Claims 1, 2, 6-10, and 13-22 are pending.
Claims 8-10 and 13-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/21/2026.
Claims 1, 2, 6, and 7 are under examination on the merits.
Notes on the Prior Art
The closest prior art is Mamonkin et al. (WO 2016/172606, international publication date: 10/27/2016). Mamonkin et al. teach “methods and compositions related to immunotherapy that targets CD5. In particular embodiments, immune cells engineered to comprise a chimeric antigen receptor (CAR) that targets CD5 are contemplated, and uses thereof. In particular embodiments, the immune cells expressing the CAR do not commit fratricide to any great extent against T cells that express CD5 and which are endogenous to an individual receiving the immune cells.” See Abstract. At [0056], Mamonkin et al. teach that the CAR of the invention does not employ 4-1BB signaling, as 4-1BB signaling can enhance fratricide of cells that express a CAR. The instant claims recite a method of reducing fratricide during the manufacture of immune cells that express a chimeric NKG2D receptor; however the instant claims recite the reduction of fratricide by inhibiting NKG2D signaling, which is a different mechanism than 4-1BB signaling. As such the teachings of Mamonkin et al. do not anticipate the claimed invention. The claimed invention is also not an obvious variant of the invention of Mamonkin et al. The claims are therefore free of the prior art.
Claim Rejections
35 U.S.C. 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 6, and 7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1 is drawn to a method of reducing and/or preventing fratricide during manufacturing of immune cells expressing a chimeric NKG2D receptor, comprising functional inhibition of NKG2D signaling during the manufacturing process of the cells. Claim 2 limits claim 1 by specifying that functional inhibition of NKG2D signaling is achieved by one or more of:
a. permanent or transient inhibition of one or more of the NKG2D ligands of the immune cells;
b. transient inhibition of the chimeric NKG2D receptor; or
c. transient inhibition of downstream signaling of the chimeric NKG2D receptor.
The claims recite methods that involve the functional inhibition of NKG2D signaling, and the claims encompass a genus of agents that are capable of functionally inhibiting NKG2D signaling. Lanier et al. (WO 2005/097160, international publication date: 10/20/2005, IDS) teach that various agents may be used to inhibit NKG2D signaling, including 1) antibodies, nucleic acids, or small molecules that inhibit NKG2D or DAP10 production in a cell, 2) peptides or small molecules that interfere with the formation or function of the NKG2D-DAP10 complex, and 3) small molecules that alter NKG2D signal transduction. See p. 15. One skilled in the art would appreciate that any of said agents may be used to inhibit NKG2D signaling. At [0015], Spies et al. (US PG PUB 2007/0248607, publication date: 10/25/2007, IDS) suggest that NKG2D signaling may be inhibited by administering soluble MIC (an NKG2D ligand) or a MIC fragment. One skilled in the art could envision other agents that would be expected to inhibit NKG2D signaling, including at least 1) antibodies or siRNA molecules specific for enzymes that are involved in NKG2D signal transduction, 2) small molecule inhibitors of enzymes that are involved in NKG2D signal transduction, or 3) antibodies that block NKG2D signaling by binding to either NKG2D or one or more of the known NKG2D ligands. Accordingly the claims encompass a broad genus of molecules/methods that would be expected to inhibit NKG2D signaling. Throughout the specification, support is provided for various inhibitors of NKG2D signaling, including 1) shRNA or antibody molecules specific for the NKG2D receptor or one or more ligands of the NKG2D receptor, 2) inhibition of PI3K signaling using a PI3K inhibitor, such as LY294002 and idelalisib, and 3) genetic knockdown of one or more NKG2D ligands; however in view of this disclosure, Applicant is claiming a broad genus of molecules/methods that inhibit NKG2D signaling, and given the variety of means by which NKG2D signaling may be inhibited one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed. Accordingly Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed multiple species within the genus of NKG2D signaling inhibitors claimed, as discussed above; however given the substantial variation comprised within the claimed genus, the disclosure of said species is not sufficiently representative of the entire genus. Furthermore Applicant has not disclosed relevant, identifying characteristics of agents that inhibit NKG2D signaling
Although screening techniques can be used to isolate agents capable of inhibiting NKG2D signaling, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
With respect to the recitation of a chimeric NKG2D receptor in claims 1-14, it is noted that the term “chimeric NKG2D receptor” comprises a broad genus of molecules having different structures. For example Sadelain et al. (Cancer Discovery, 388-398, 2013, IDS) teach that T cells that comprise a chimeric antigen receptor may comprise different intracellular signaling components, see Figure 1. While first generation CAR T cells typically comprised an antigen-binding moiety linked to CD3ζ, second and third generation CAR T cells may comprise intracellular signaling components from ICOS, 4-1BB, OX-40, or Lck. At p. 2 of the instant specification, NKG2D CARs are described that comprise NKG2D linked to linked to CD3ζ; however this disclosure does not provide adequate written description for the entire genus of chimeric NKG2D receptors. Therefore the claimed genus of chimeric NKG2D receptors has not been adequately described.
Accordingly it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Nonstatutory 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, 2, 6, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, and 7 of U.S. Patent No. 11,639,496.
Although the claims at issue are not identical, they are not patentably distinct from each other, because both claim sets recite a method of reducing fratricide during the manufacture of immune cells that express a chimeric NKG2D receptor, comprising functional inhibition of NKG2D signaling during the manufacturing process, which results in at least one of (i) permanent or transient inhibition of one or more of the NKG2D ligands of the immune cells; (ii) transient inhibition of the chimeric NKG2D receptor; or (iii) transient inhibition of downstream signaling of the chimeric NKG2D receptor, see conflicting claims 1 and 2.
The instant claims 6 and 7 are not patentably distinct from conflicting claims 6 and 7, because conflicting claims 6 and 7 recite that 1) functional inhibition is achieved using one or more shRNAs or siRNAs or an antibody against the NKG2D receptor or against one or more of said NKG2D ligands and 2) immune cells of the invention comprise one or more of T cells, NK cells, NKT cells, stem cells and iPSCs.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
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.
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/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642