DETAILED ACTION
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 without traverse of tandem single chain scFv bispecific antibody of SEQ ID NO: 89, having VH/VL of SEQ ID Nos 36/37 and CDRS of SEQ ID NO: 16-21, and bevacizumab as the specific of VEGF inhibitor, in the reply filed on 5/19/26 is acknowledged. Claims 6 and 16 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Claims 1-5, 7-15 and 17-20 read on the elected invention and are being acted upon.
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.
Claims 1-5, 7-15 and 17-20 are 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.
Claim 1 is directed to a method for treating gynecologic cancer comprising administering an anti-MUC16 x CD3 bispecific antibody or “antigen binding fragment thereof”, wherein the antibody or antigen binding fragment comprising a first antigen binding stie that binds to MUC16 comprising an MUC16 ectodomain, wherein the ectodomain sequence consists of SEQ ID NO: 95. The scope of the antigen binding fragments thereof is unclear and indefinite. Specifically, it is not clear whether the claims would encompass an antibody fragment comprising only the binding arm that binds to MUC16, or whether the claims require antigen binding fragments that retain binding to both antigens, i.e. that bind to both MUC16 and CD3. The specification on page 15 defines the term “antigen binding fragment” as referring to a fragment of the whole immunoglobulin structure which possesses a part of a polypeptide responsible for binding to antigen. In the instant claims, the immunoglobulin structure is a bispecific antibody that binds to CD3 and MUC16, and the definition of the specification would imply that the antigen binding fragment possesses the part responsible for binding to antigen, i.e. for binding to both CD3 and MUC16. However, dependent claim 10 recites that the anti-MUC16xCD3 bispecific antibody or antigen binding fragment comprises a second binding site that specifically binds to T cells. If claim 1 is intending to encompass only antibody fragments that bind to both CD3 and MUC16, claim 10 would fail to further limit claim 1 and in fact would be broader than claim 1. See also claim 7, which recites that the antigen binding fragment is, for example, an scFv, which also appears to encompass a single MUC16 scFv. Given the dependent claims, for the purposes of examination, the scope of claim 1 is being interpreted to encompass antigen binding fragments thereof that bind to only MUC16. For example, an scFv that binds to MUC16 would be an antigen binding fragment of a bispecific antibody that binds to MUC16 and CD3.
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.
Claim(s) 1-2, 7-8, 10, 14-15, 18, and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20190389966 (of record).
The ‘966 publication teaches a method of treating ovarian cancer in a subject in need thereof comprising administering a MUC16 x CD3 bispecific antibody in combination with a VEGF inhibitor (see abstract, paragraphs 10-14, in particular). The ‘966 publication teaches that the VEGF inhibitor can be bevacizumab (i.e. an antibody, see paragraph 98, in particular). The ’966 publication teaches that the bispecific format can be scFv based (see paragraph 89, in particular). The ‘966 publication teaches that the antibodies are humanized or human. The ‘966 publication teaches that the antibodies are administered intravenously (see paragraph 12, in particular).
The present claims recite that the antibody binds to a MUC16 polypeptide “comprising” a MUC16 ectodomain sequence, wherein the ectodomain sequence “consists of” SEQ ID NO: 95. The ‘966 publication teaches that said bispecific antibody is BSMUC16/CD3-001, and that the antibody binds to human MUC-16 on ovarian cancer cells expressing the membrane proximal region of MUC-16, but does not bind to the CA-125 portion of MUC-16 (see pages 18-19, in particular). Therefore, the bispecific antibodies of the ‘966 publication inherently bind to a MUC16 polypeptide comprising a MUC16 ectodomain sequence consisting of SE QID NO: 95 (which is in the membrane proximal region and not in the CA-125 portion). Said antibodies also inherently would bind to a MUC16 polypeptide having SEQ ID NO: 3.
See MPEP, 2111.03, the “consisting of” phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. Mannesmann Demag Corp.v.Engineered Metal Products Co., 793 F.2d 1279, 230 USPQ 45 (Fed. Cir. 1986). See also In re Crish, 393 F.3d 1253, 73 USPQ2d 1364 (Fed. Cir. 2004) (The claims at issue “related to purified DNA molecules having promoter activity for the human involucrin gene (hINV).” Id., 73 USPQ2d at 1365. In determining the scope of applicant’s claims directed to “a purified oligonucleotide comprising at least a portion of the nucleotide sequence of SEQ ID NO:1 wherein said portion consists of the nucleotide sequence from … to 2473 of SEQ ID NO:1, and wherein said portion of the nucleotide sequence of SEQ ID NO:1 has promoter activity,” the court stated that the use of “consists” in the body of the claims did not limit the open-ended “comprising” language in the claims (emphases added). Id. at 1257, 73 USPQ2d at 1367.
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.
Claims 1-2, 7-12, 14-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 20180112001, in view of US 20090022738.
The ‘001 publication teaches a method of treating ovarian cancer in a subject in need thereof comprising administering a MUC16 antibody, such as a MUC-16 x CD3 bispecific antibody (see paragraphs 60, in particular). The ‘001 publication teaches that the cancer treatment can be combined with a VEGF inhibitor (see paragraph 309, in particular). The ‘001 publication teaches that the VEGF inhibitor can be bevacizumab (i.e. an antibody, see paragraph 309, in particular). The ’001 publication teaches that the bispecific format can be scFV based (see paragraph 89, in particular). The ‘001 publication teaches that the antibodies are humanized or human and monoclonal (see paragraph 178, in particular). The ‘966 publication teaches that the antibodies are administered intravenously (see paragraph 297, in particular). The ‘001 publication teaches that the bispecific antibody can be administered in the same composition with the second therapeutic agent (see paragraph 102, i.e. simultaneously). The ‘001 publication taches that the MUC16 bispecific antibodies can bind to an epitope within the membrane proximal region corresponding to 13810-14451 of SEQ ID NO: 1899, or that the antibodies can bind within residues 14321 to 14464 of SEQ ID NO: 1899 (see the claims, and paragraphs 44 and 105, in particular). SEQ ID NO: 95 of the instant application corresponds to residues 14394-14451 of SEQ ID NO: 1899. Thus, it would also be obvious to use an antibody that binds to an epitope within 14394-14451 of SEQ ID NO: 1899 (i.e. to SEQ ID NO: 95), since the ‘001 publication teaches antibodies can bind within residues 13810-14451 or 14321-14464 and choosing from within the regions defined in the prior art would be well within the purview of the ordinary artisan.
The references differ from the claimed invention in that they do not explicitly teach a CD3 binding arm having SEQ ID NO: 72 or a tandem scFV bispecific.
The ‘738 publication teaches a CD3 binding arm comprising SEQ ID NO: 19 that can be used in CD3 bispecific antibodies that target a tumor antigen, which is identical to SEQ ID NO: 72 of the instant application (See paragraphs 2-40, in particular). The ‘738 publication teaches treating tumors diseases and that the CD3 binder has advantages in that is cytotoxically active and deimmunized so that it exhibits reduced immunogenicity. The ‘738 publication teaches that the bispecific constructs can comprises of a first scFV targeting CD3 and a second scFV targeting the tumor antigen joined by a linker (i.e. a tandem scFV, See paragraphs 40-41, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the CD3 binding arm of the ‘738 publication, in the CD3xMUC16 bispecific antibody of the ‘001 publication. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘738 publication teaches that it has advantages for treating tumors diseases in that it is cytotoxically active and deimmunized so that it exhibits reduced immunogenicity. Furthermore, selecting from known scFV based bispecific constructs, such as a tandem scFV, would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
Regarding 19, selecting from known routes for administration of antibodies for use in bevacizumab administration, such as intravenously would be routine and well within the purview of the ordinary artisan.
Claims 1-2, 7-8, 14-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 9,169,328, in view of US 20080311134.
The ‘328 patent teaches a method of treating ovarian cancer comprising administering to a subject in need thereof an antibody, or antigen binding fragment, that binds to MUC16, wherein the antibody binds to an ectodomain portion of MUC16 sequence of SEQ ID NO: 2, which corresponds to residues 32-49 of SEQ ID NO: 95 of the instant application (see columns 1-4, in particular). The ‘328 patent teaches that the antigen binding fragment is monoclonal and is an scFV and can be humanized (see column 4, in particular). The ‘328 patent teaches administration before or concomitantly with other types of drugs, and administration intravenously (see column 27, in particular). Thus, the antibody or biding fragments of the prior art bind to a MUC16 polypeptide consisting of SEQ ID NO 95, or a polypeptide having SEQ ID NO: 3, and also would be within the scope of a an “antigen binding fragment” of a bispecific anti-MUC16 x CD3 bispecific antibody.
The reference differs from the claimed invention in that it does not explicitly teach administering a VEGF-inhibitor.
The ‘134 publication teaches a method of treating ovarian cancer comprising administering an anti-MUC16 antibody in combination with a chemotherapeutic, wherein a chemotherapies includes a VEGF-inhibitor such as bevacizumab (see claims 47-49, paragraphs 51-52, paragraph 85 and paragraphs 196). The ‘134 publication teaches an scFV (see paragraph 72, in particular). The ‘134 publication teaches simultaneous or sequential administration (see paragraph 338, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to further administer a VEGF inhibitor such as bevacizumab, as taught by the ‘134 publication, as the other type of drug for treating ovarian cancer in the method of the ‘328 patent. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success to improve treatment efficacy, since the ‘134 publication teaches that VEGF-inhibitor such as bevacizumab can be combined with anti-MUC-16 antibodies for treatment of ovarian cancer.
Claims 1-5, 7-15 and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/102555 (of record), in view of US 20180112001 and Napoletano, 2019.
WO 2020/102555538 teaches a method of treating ovarian cancer in a patient in need thereof comprising administering a therapeutically effect amount of an anti-MUC16 x CD3 bispecific construct comprising SEQ ID NO: 22, which is 100% identical to SEQ ID NO: 89 of the instant application. Said bispecific construct is a tandem scFV comprising the same MUC-16 and CD3 VH and VL as recited in the instant claims, and also binds to a MUC16 polypeptide comprising an MUC16 ectodomain sequence consisting of SEQ I DNO: 95, or a MUC-16 polypeptide having SEQ ID NO: 3. WO 2020/102555 teaches that the antibodies are human or humanized (See pages 74-75, 85-89, 98-99, in particular). WO 2020/102555 teaches intravenous or intraperitoneal administration (See page 78, in particular). WO 2020/102555 teaches combination therapy comprising said antibody and one or more additional therapeutic agents for treating cancer (See page 79-80, in particular). WO 2020/102555 teaches that the combination therapy can be administered concurrently or sequentially (See page 80, in particular).
The reference differs from the claimed invention in that it does not specifically teach a VEGF inhibitor as the second therapeutic agent.
The ‘001 publication teaches a method of treating ovarian cancer in a subject in need thereof comprising administering a MUC16 x CD3 bispecific antibody in combination with a VEGF inhibitor (see paragraphs 60 and 309, in particular). The ‘001 publication teaches that the VEGF inhibitor can be bevacizumab (i.e. an antibody, see paragraph 309, in particular).
Napoletano teach that bevacizumab is effective in ovarian cancer and acts to normalize tumor vasculature and improve immune fitness. Napoletano teach that combining bevacizumab with immunotherapy can provide immunological synergisms (see page 1, in particular). Napoletano teach administration of bevacizumab by an intraperitoneal route (See page 2, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to administer bevacizumab, as taught by the ‘001 publication and Napoletano, as a second therapeutic agent in the method of treating ovarian cancer taught by WO 2020/102555. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘001 publication teaches that it can be used in combination therapy with MUC-16xCD3 bispecific antibodies, and Napoletano teach that bevacizumab is effective in ovarian cancer and acts to normalize tumor vasculature and improve immune fitness. Napolitano teach that combining bevacizumab with immunotherapy can provide immunological synergisms
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, 7-12, 14-15, and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30, 39, 45-60 of U.S. Patent No. 9,169,328, or claims 33-57 of US 10,759,869, in view of US 20180112001, US 20090022738 and Napoletano, 2019.
The patents claim a method of treating ovarian cancer comprising administering an antibody or antigen binding fragment thereof which binds to a MUC16 polypeptide of SEQ ID NO; 2, wherein the antibody is monoclonal or humanized, or an scFv fragment. SEQ ID NO: 2 is an epitope within SEQ ID NO: 95 of the instant application and therefore the antibodies or antibody fragments would inherently bind to a MUC16 polypeptide having an ectodomain consisting of SEQ ID NO: 95, or to a polypeptide comprising SEQ ID NO: 3. Said antibodies or antibody fragments would comprise an “antigen binding fragment” of a CD3x MUC16 bispecific antibodies. Alternatively, it would also be obvious to use said MUC-16 antibody as a bispecific antibody based on the teachings of the ‘001 publication, which teaches that MUC-16xCD3 bispecific antibodies are useful for activating T cells and treating ovarian cancer. Selecting the CD3 binding arm of the ‘738 publication would be obvious for the reasons set forth above. Furthermore, it would be obvious to further administer bevacizumab based on the teachings of the ‘001 publication and Napoletano for the reasons set forth above, and the administration routes and regimens of the instant claims are also obvious based on the teachings of the ‘001 publication and Napoletano.
Claims 1-2, 7-12, 14-15, and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-18 of U.S. Patent No. 11,834,513, in view of US 20180112001, US 20090022738 and Napoletano, 2019.
The ‘513 patent claims a method of treating ovarian cancer comprising administering an antibody or antigen binding fragment thereof which binds to a MUC16 polypeptide of SEQ ID NO; 1 wherein the antibody is monoclonal or humanized, or an scFv fragment. Said SEQ ID NO: 1 corresponds to residues 1-17 of SEQ ID NO: 95 of the instant application. and therefore the antibodies or antibody fragments would inherently bind to a MUC16 polypeptide having an ectodomain consisting of SEQ ID NO: 95, or to a polypeptide comprising SEQ ID NO: 3. Said antibodies or antibody fragments would comprise an “antigen binding fragment” of a CD3x MUC16 bispecific antibodies. Alternatively, it would also be obvious to use said MUC-16 antibody as a bispecific antibody based on the teachings of the ‘001 publication, which teaches that MUC-16xCD3 bispecific antibodies are useful for activating T cells and treating ovarian cancer. Selecting the CD3 binding arm of the ‘738 publication would be obvious for the reasons set forth above. Furthermore, it would be obvious to further administer bevacizumab based on the teachings of the ‘001 publication and Napoletano for the reasons set forth above, and the administration routes and regimens of the instant claims are also obvious based on the teachings of the ‘001 publication and Napoletano.
Claims 1-5, 7-15 and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,168,696, in view of 20180112001, and Napoletano, 2019.
The ‘696 patent claims a an antibody or antigen binding fragment thereof which binds to a MUC16 wherein the antibody comprises CDRs or VH and VL of SEQ ID NO: 2 and 3, wherein said antibody is a MUC-16 bispecific antibody, such as a tandem scFV, and wherein the bispecific antibody further comprises a CD3 antigen binding domain. Said SEQ ID NO: 2 and 3 are identical to SEQ ID NO: 36 and 37 of the instant claims, i.e. they bind to a MUC-16 ectodomain consisting of SEQ ID NO: 95. The specification of the ‘696 patent specifically discloses that said bispecific antibodies includes SEQ ID NO: 22. Thus, the claims of the ’696 patent cover the bispecific antibody of SEQ ID NO: 22, which is identical to SEQ ID NO: 89 of the instant claims. It would be obvious to administered said bispecific antibody in combination with bevacizumab to treat ovarian cancer based on the teachings of the ‘001 publication and Napoletano for the same reasons set forth above.
Claims 1-2, 7-12, 14-15, and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 10 of 12,617,866, claims 1-51 of 11,066,480, or claims 1-15 of 12,466,894, in view of US 20180112001, US 20090022738 and Napoletano, 2019.
The patents all claim a an anti-MUC16 antibody moiety that comprises a human/humanized VH and VL comprising specifically identified CDRs or VH and VL. Said antibodies are disclosed to inherently binds to a mUC16c114 polypeptide which comprises an ectodomain consisting of SEQ ID NO: 95 of the instant application. The patents also claims an anti-MUC-16 construct that is a bispecific antibody, and claim methods of treating ovarian cancer. It would be obvious to use a bispecific MUC-16 x CD3 and to administer said bispecific antibody in combination with bevacizumab based on the teachings of the ‘001 publication and Napoletano for the same reasons set forth above. Selecting the CD3 binding arm of the ‘738 publication would be obvious for the reasons set forth above.
Claims 1-5, 7-15 and 17-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending application No. 18/983,001, in view of 20180112001, and Napoletano, 2019.
The ‘001 application claims a MUC16 antibody comprising CDRs of SEQ ID NO: 2 and 3 and also claims that said antibody is a MUC-16 bispecific antibody, such as a tandem scFv, wherein the bispecific antibody further comprises a CD3 antigen binding domain. Said SEQ ID NO: 2 and 3 are identical to SEQ ID NO: 36 and 37 of the instant claims, i.e. they bind to a MUC-16 ectodomain consisting of SEQ ID NO: 95. The specification of the ‘001 application specifically discloses that said bispecific antibodies includes SEQ ID NO: 22. Thus, the claims of the ‘001 application cover the bispecific antibody of SEQ ID NO: 22, which is identical to SEQ ID NO: 89 of the instant claims. It would be obvious to administered said bispecific antibody in combination with bevacizumab to treat ovarian cancer based on the teachings of the ‘001 publication and Napoletano for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
No claim is allowed.
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.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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