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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 10/17/2025 is acknowledged. Claims 1-4, 6-7, 9-17, 19, 21-49 are pending. Upon review and reconsideration, the restriction between Group I and Group III mailed 07/23/2025 is removed.
Claims 23-28, 41-43, and 47-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 1-4, 6-7, 9-17, 19, 21-22, 29-40, 44-46 are pending and are under consideration.
Claim Objections
Claims 2, 4, and 7 are objected to because of the following informalities: Each of the claims recite “and/or” when further defining structural portions of the bispecific antibody. And/or are coordinating conjunctions. Use of the term “and” is definite as it adds information. Use of the term “or” presents a choice. However, as currently claimed, the structural phrases connected by the conjunctions don’t appear to be rendering a choice. For example, in claim 2 it doesn’t appear that the VL comprising an amino acid sequence at least 95% identical to SEQ ID NO:11 is something to choose. Thus, inclusion of the conjunction “or” renders the claims confusing and somewhat ambiguous. Applicant is requested to cancel the term “or” or applicant can offer rationale as to why the two conjunctions are necessary.
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 1-4, 6-7, 9-10, 12-14, 16-17, 19, 21-22, and 30-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-14, 17-18, 25-26, 32, and 39-40 of copending Application No. 18/901300 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the reference application comprises the same 6 CDRs that bind to CD3 and the same 6 CDRs that bind to the Folate receptor 1 antigen (FolR1) compared to the reference application’s CDRs in Claim 15 and Claim 25. Also, Claim 21 of the current application comprises identical CDRs (SEQ IDs 124-126 and 8-10). See comparison chart below and reference claim set of 12/10/2024 of the 18/901300 application.
Target antigen CD3/FolR1
Bispecific Ab of current Claim 1
Bispecific Ab in ‘300 (Claims 17 and 25)
HCDR1 CD3/FolR1
SYAMN / NAWMS
(SEQ IDs:2/124)
Identical to SEQ ID NOs:1/11
HCDR2 CD3/FolR1
RIRSKYNNYATYYADSVKG/
RIKSKTDGGTTDYAAPVKG
(SEQ IDs 3/125)
Identical to SEQ ID NOs:2/12
HCDR3 CD3/FolR1
HTTFPSSYVSYYGY /
PWEWSWYDY
(SEQ ID NOs: 5/126)
Identical to SEQ ID NOs:4/13
LCDR1 CD3/FolR1
GSSTGAVTTSNYAN
SEQ ID NO:8
Identical to SEQ ID NO:7
LCDR2 CD3/FolR1
GTNKRAP
SEQ ID NO:9
Identical to SEQ ID NO:8
LCDR3 CD3/FolR1
ALWYSNLWV
SEQ ID NO:10
Identical to SEQ ID NO:9
Claim 2 of the pending application comprises the VH (SEQ ID: 7) and VL (SEQ ID NO:11) chains that are specific to CD3. This matches to Claim 18 of the reference application because the VL and VH regions are identical.
Claim 3 and 22 of the pending application comprise the VH (SEQ ID: 123) and VL (SEQ ID NO:11) chains that are specific to FolR1. This matches to Claim 26 of the reference application because the VL and VH regions are identical.
Regarding claim 17 of the current application, wherein the Fc domain is an IgG1 Fc domain, such a domain is an obvious variation to any one of skill in the art.
The remaining claims are drawn to similar generic structures, pharmaceutical compositions and methods of treating a disease and cancer which are obvious variations over the co-pending application.
And, while the reference claim includes a “masking moiety” and a specific linker, both sets of claims encompass open language (e.g., “comprising”) such that the entire scope of the reference claim falls within the scope of the examined claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112
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 31-33 and 45 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims are broadly drawn to administration of a bispecific antibody capable of binding to CD3 and FoIR1 for the purposes of treating a disease. Thus, the broadest reasonable interpretation of the claims encompasses the treatment of any disease known to man. Thus the “disease pool” represents a large genus of diseases that could differ at least in etiologies, pathologies, and mechanisms. This could include diseases as diverse as Alzheimer’s, heart disease, COVID-19, diabetes, Parkinson’s, Lyme disease, ADHD, and cystic fibrosis. The specification teaches [0140] that “treatment” (and grammatical variations thereof such as “treat” or “treating”) refers to clinical intervention in an attempt to alter the natural course of a disease in the individual being treated. The specification further teaches [0007] that CD3 has been extensively explored as drug target. Monoclonal antibodies targeting CD3 have been used as immunosuppressant therapies in autoimmune diseases such as type I diabetes, or in the treatment of transplant rejection. Regarding FoIR1, the specification teaches [0009] FOLR1 is expressed on epithelial tumor cells of various origins, e.g., ovarian cancer, lung cancer, breast cancer, renal cancer, colorectal cancer, endometrial cancer and that several approaches to target FOLR1 with therapeutic antibodies, such as farletuzumab, antibody drug conjugates, or adoptive T cell therapy for imaging of tumors have been described. However, there does not appear to be any discussion regarding treatment of disease with a bispecific antibody, particularly ones that target CD3 and FoIR1. Ma et al. (Front. Immunol, Vol.12, May 2021) provide a review of bispecific antibodies including their clinical applications wherein the authors teach that over 86% of the bispecific antibodies to date are used in cancer treatment (page 10, 2nd column). While there is some discussion of bispecific antibodies to treat diabetes, Alzheimer’s, and pneumonia; these diseases are not representative of the plurality of possible diseases as currently claimed. Thus, one of skill in the art, based on the knowledge of treating diseases with bispecific antibodies at the time of filing, would not believe applicants were in possession of the genus of diseases to be treated.
A description of a genus of may be achieved by means of a recitation of a representative number of species, defined by structure, falling within the scope of the genus. However, the instant specification fails to provide sufficient descriptive information, such as possession of a representative number of diseases that are treated with the bispecific antibody. The specification further fails to disclose a representative number of diseases where dual binding of CD3 and FoIR1 are associated with treatment of disease. In the instant case, only one disease, cancer, (see Figure 31) appears to meet the written description. Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly diverse and variant, the disclosure of only one disease is insufficient to describe the large genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe and enable the genus as broadly claimed.
Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991) clearly states “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). As discussed above, the skilled artisan cannot envision the genus of diseases that would be treated by the bispecific antibody, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it.
Claim Objections
Claims 11, 15, and 46 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.
Allowable Subject Matter
Claims 37-40, and 44 are allowed.
Pertinent Reference Not Relied Upon
US 2024/0002498 (Avanzino et al., filed Nov 18, 2020) teaches [0219-0222] a fully human bispecific antibody that binds to FolR1 and CD3 referred to as TNB-928B that induces tumor regression.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643