CTNF 18/284,586 CTNF 81547 DETAILED ACTION 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Applicant’s election of group I, a multispecific antibody that binds NKG2D, claims 1-5, 9-12, 14-15, 18-19, 23, and 38, in the reply filed on 5/15/26 is acknowledged. Applicant has further elected SEQ ID NO: 2 and 3 as species of VH/VL, and BCMA as the species of tumor antigen. Upon reconsideration, the species election as the the species of VH/VL for the NKG2D binding domain is withdrawn. Claims 6-8 and 40 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species. Claim 34 is withdrawn as being directed to a non-elected invention. Claims 1-5, 9-12, 14-15, 18-19, 23, and 38 are being acted upon. 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 19 is indefinite in the recitation of an antibody that is a “bipod-scaffold” configuration or a “Morrison-scaffold” configuration. The specification does not define the terms and the scope of the claimed configuration cannot be established. The specification discloses that in some embodiments a bipod scaffold configuration can have a first binding domain that is a Fab region and a second binding domain is a an scFv region, and in some embodiments the Morrison scaffold comprises two Fab regions and a second binding domain comprises tow scFV regions. However, this is merely exemplary and is not a limiting definition and the scope of the claimed configurations. For example, would the Morrison scaffold configuration encompass a configuration wherein the scFV are linked to the Fab region, or are the claims limited to the specific structure in Fig. 4 wherein the scFV are linked to an IgG1 Fc region. 07-30-01 AIA The following is a quotation 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 35 U.S.C. 112 (pre-AIA), first paragraph: 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. 07-31-01 AIA Claim 23 is 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. Specifically, there is insufficient written description to demonstrate that applicant was in possession of the claimed genus of multispecific antibodies that function to induce NK cell dependent cytotoxicity of tumor cells in vitro with an IC50 of less than about 500 pM . 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 MPEP 2163. The instant claim is directed to a genus of multispecific antibodies with the function of inducing NK cell dependent cytotoxicity of tumor cells in vitro with an IC50 of less than about 500 pM. The claims encompass a genus of different multispecific or bispecific structures as well as a genus of different target antigens including any antigen expressed on any tumor cell and any antigen expressed on NK cells. For example, the claims would encompass a genus of different multispecific antibody formats and a enormous genus of different VH and VL specific for a wide range of different first and second antigens. The state of the art is such that the antibody repertoire in humans is at least 10 11 , with a large degree of diversity in both heavy and light chains (see Janeway). See also Rabia, 2018, which teaches that the maximal chemical diversity of antibody CDRs is unimaginably large and is extremely challenging to define the sequence determinant of antibody specificity (see page 4). The specification does not disclose a correlation between structure and the function of inducing NK cell dependent cytotoxicity of tumor cells in vitro with an IC50 of less than about 500 pM, nor does the specification disclose a representative number of species. The specification discloses two species, NG2BB10 and NG2BB9, having a particular bispecific structure shown in Fig. 4 with a IgG1 constant region., and which comprise the VH and VL of SEQ ID NO 2-3 or 34-35, binding to NKG2D, and a second VH/VL of SEQ ID NO: 99/100 that binds to BCMA. Other constructs tested had IC50 values in the nanomolar range or higher, are not representative of antibodies with IC50 less than 500 pM as recited in the present claim. The disclosed species are not representative of the functional genus claimed, which encompass any VH/VL that binds to any NK cell antigen and any tumor antigen and having any multispecific antibody structure. The instant application has not provided a sufficient description showing possession of the necessary 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 genus of antibodies and inhibitors encompassing various structures, specificities and functions. Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)). Vas-Cath Inc. v. Mahurkar , 19 USPQ2d 1111, makes clear that "applicant must 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." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.) Also, it is noted that the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co ., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004). Meeting the written description threshold requires showing that the applicant was in “possession” of the claimed invention at the time of filing. Vas-Cath, 935 F.2d at 1563-1564. Support need not describe the claimed subject matter in exactly the same terms as used in the claims. Eiselstein v. Frank, 52 F.3d 1035, 1038 (Fed. Cir. 1995). This support cannot be based on obviousness reasoning – i.e., what the written description and knowledge in the art would lead one to speculate as to modifications the inventor might have envisioned, but failed to disclose. Lockwood v. American Airlines , Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997). Ariad points out, the written description requirement also ensures that when a patent claims a genus by function, the specification recites sufficient materials to accomplish that function - a problem that is particularly acute in biological arts." Ariad, 598 F.3d at 1352-3. Given the claimed broadly class of antibodies, in the absence of sufficient disclosure of relevant identifying characteristics, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech , Inc. (Fed. Cir. 2014) and the specification at best describes plan for making antibodies with the “limitations above” and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011). There is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). Thus, one of skill in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus. See Eli Lilly , 119 F. 3d 1559, 43, USPQ2d 1398 . 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15-aia AIA Claim(s) 1-3, 9-12, 15, 18-19 , is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US 2019/0375838 . The ‘838 publication teaches a multispecific antibody that binds to BCMA and NKG2D receptor on NK cells (see page 1, in particular). The ‘838 publication teaches that the multispecific antibody is an IgG1 (See paragraphs 97-98, in particular). The ‘838 publication teaches bispecific antibody constructs comprising a Fab binding arm and a scFv binding arm, i.e. a “bipod-scaffold” configuration, see Fig. 2, in particular . 07-15-aia AIA Claim(s) 1-3, 9-11, 15, 18-19, 23 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by WO2018152518 . WO2018152518 teaches a multispecific antibody that binds to tumor associated antigen and NKG2D receptor on NK cells (see page 2, in particular). WO2018152518 teaches that the multispecific antibody is an IgG1 (See paragraphs 111-115, in particular). WO2018152518 teaches bispecific antibody constructs comprising a Fab binding arm and a scFv binding arm, i.e. a “bipod-scaffold” configuration, see Fig. 2, in particular). WO2018152518 teaches that the multispecific antibody induces NK cell cytotoxicity of tumor cells in vitro with an IC50 of less than about 500 pM (see Figs. 23, 29, or 32, in particular) . 07-15-aia AIA Claim(s) 1-3, 9-11, 14, 18, 23 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US 2018/0237519 . The ‘519 publication teaches a bispecific antibody that binds to tumor associated antigen and NKG2D receptor on NK cells (see page 2 and 6, in particular). The ‘678 publication teaches that the bispecific antibody is an IgG1 (See paragraphs 111-115, in particular). The ‘519 publication teaches that the bispecific antibody can comprise humanized antibody binding domains (See page 6, in particular). The ‘519 publication teaches that the antibody induces NK cell cytotoxicity of tumor cells in vitro with an IC50 of 3 x 10 -12 , i.e. less than about 500 pM (see page 16, in particular) . 08-33 AIA 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 1-3, 9-11, 14-15, 18-19, 23, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of 18/307,076, claim 10 of 18/307,127, claim 16 of 17/906,040, claim 10 of 18/307,146, claim 10 of 18/249,807, and claim 4 of 18/561,512, all copending Applications, in view of US 2020/0231678 and US 2018/0237519. The applications all claim a bispecific antibody binding to a tumor cell associated surface antigen and NKG2D. The limitations regarding using a humanized antibody, IgG1, the particular bispecific format, cytotoxic activity are all obvious optimizations based on the teachings of the ‘678 publication and the ‘519 publication which teach the claimed bispecific scaffold formats, humanization, IgG1, and the claimed cytotoxicity. This is a provisional nonstatutory double patenting rejection. Claims 1-3, 9-12, 14-15, 18-19, 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 226 of 18/208,361, in view of US 2020/0231678 and US 2018/0237519. The ‘361 application claims a bispecific antibody binding to GPRC5d and NKG2D. The limitations regarding using a humanized antibody, IgG1, the particular bispecific format, cytotoxic activity are all obvious optimizations based on the teachings of the ‘678 publication and the ‘519 publication which teach the claimed bispecific scaffold formats, humanization, IgG1, and the claimed cytotoxicity. This is a provisional nonstatutory double patenting rejection. Claims 1-3, 9-12, 14-15, 18-19, 23, are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4, and 6 of 18/430,862 or 17/322,93, in view of US 2019/0375838, US 2020/0231678 and US 2018/0237519. The applications claim a bispecific antibody binding to antigens that include BCMA and NKG2D, and selecting BCMA and NKG2D would also be obvious based on the teachings of the ‘838 publication. The limitations regarding using a humanized antibody, IgG1, the particular bispecific format, cytotoxic activity are all obvious optimizations based on the teachings of the ‘678 publication and the ‘519 publication which teach the claimed bispecific scaffold formats, humanization, IgG1, and the claimed cytotoxicity. This is a provisional nonstatutory double patenting rejection. 08-36 AIA Claim s 1-3, 9-11, 14-15, 18-19, 23, are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1, 17-18 of U.S. Patent No. 11,149,094 in view of in view of US 2019/0375838, US 2020/0231678 and US 2018/0237519 . The patent claims a multispecific or bispecific antibody binding to two or more antigens, wherein one of the antigens is NKG2D. Selecting BCMA as the second antigen would be obvious, since the ‘838 publication teaches that it is useful second target in NKG2D bispecific antibodies for targeting tumor cells. The limitations regarding using a humanized antibody, IgG1, the particular bispecific format, cytotoxic activity are all obvious optimizations based on the teachings of the ‘678 publication and the ‘519 publication which teach the claimed bispecific scaffold formats, humanization, IgG1, and the claimed cytotoxicity. This is a provisional nonstatutory double patenting rejection. Claim 38 is allowed. Claims 4-5 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. The prior art does not teach or suggest an NKG2D antibody having a VH and VL with the CDR1-3 having the SEQ ID Nos: recited in the claims. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form. Amy E. Juedes Patent Examiner Technology Center 1600 /AMY E JUEDES/Primary Examiner, Art Unit 1644 Application/Control Number: 18/284,586 Page 2 Art Unit: 1644 Application/Control Number: 18/284,586 Page 3 Art Unit: 1644 Application/Control Number: 18/284,586 Page 4 Art Unit: 1644 Application/Control Number: 18/284,586 Page 5 Art Unit: 1644 Application/Control Number: 18/284,586 Page 6 Art Unit: 1644 Application/Control Number: 18/284,586 Page 7 Art Unit: 1644 Application/Control Number: 18/284,586 Page 8 Art Unit: 1644 Application/Control Number: 18/284,586 Page 9 Art Unit: 1644 Application/Control Number: 18/284,586 Page 11 Art Unit: 1644
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