CTNF 18/035,591 CTNF 82602 DETAILED ACTION Notice of Pre-AIA or AIA Status 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. Election/Restrictions Applicant’s election without traverse of Group I (claims 1-15, 18 and 19) in the reply filed on 02/02/2026 is acknowledged. Upon further consideration, Examiner determined that all claims may be examined and the Requirement for Restriction/Election of 12/10/2025 is withdrawn. Claims 1-20 are pending and are examined. Information Disclosure Statement The information disclosure statements (IDS)s submitted on 05/05/2023, 11/13/2023 and 09/12/2024 were considered by the examiner. 06-49-06 AIA The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Priority Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Application is a National Stage entry of the PCT/CN2021/129045, filed 11/05/2021, which claims priority to the CN202011232115.5 Application, filed 11/06/2020. Claim Rejections - 35 USC § 112 07-30-01 AIA 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. 07-31-01 Claims 1-3, 16, 18, 19 and 20 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. “[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification. ’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the 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. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). (emphasis added). See also MPEP 2163.04. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the 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 to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity. Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361). In the instant case, the specification discloses specific bispecific antibodies against PD-L1 and CD47. However, the claims broadly encompass any bispecific antibody that binds PD-L1 and has the 6 CDRs comprising: (a) a VHa CDR1 comprising an amino acid sequence set forth in any one of SEQ IDNOs: 4-8; (b) a VHa CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 9-18; (c) a VHa CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 19 or 20; ( d) a VLa CDR1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 36-40; ( e) a VLa CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 41-44; and (f) a VLa CDR3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 45-48, without any indication of the structure of the second antibody of the bispecific construct. Thus, what is claimed is a genus of bispecific antibodies that bind PD-L1 and absolutely any other undisclosed antigen or epitope. Additionally, claim 16 is drawn to any PD-L1 and CD47 bispecific antibodies which have identical light chains, without any structure except SEQ ID NOs: 92 and 94 for the anti PD-L1 variable heavy chain portion of the antibody, SEQ ID NOs: 93 and 95 for the anti CD47 variable heavy chain portion of the antibody and SEQ ID NO: 96 for the variable light chain portion of the antibody. The instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses only bispecific antibodies that bind PD-L1 and CD47, with defined structures. A “representative number of species" means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The “structural features common to the members of the genus” needed for one of skill in the art to 'visualize or recognize' the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural “stepping stone” to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011). Here, the claims are directed to a genus of antigen-binding immunoglobulin molecules are defined by their desired binding to an antigen and function of such binding. It is well-known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that over hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Protein Engineering, Design & Selection 2009, 22:159-168; see, e.g., Discussion). Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies and the unlimited number of bispecific antibodies that bind PD-L1 and all the other antigens, epitopes or molecules. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera. 07-31-03 AIA Claim s 1-16, 18, 19 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for bispecific antibodies comprising full 6 CDRs sets in a set order (e.g. BsAb-36, BsAb-46, BsAb-47, BsAb-71, BsAb-71-N297A) does not reasonably provide enablement for antibodies characterized by less than a full set of CDRs . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The claims are drawn to a bispecific antibody or an antigen-binding fragment, wherein the antibody or the antigen-binding fragment comprises a variable region a specifically binding to PD-L1, wherein the variable region a comprises one or more amino acid sequences of (a)-(f): (a) a VHa CDR1 comprising an amino acid sequence set forth in any one of SEQ IDNOs: 4-8; (b) a VHa CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 9-18; (c) a VHa CDR3 comprising an amino acid sequence set forth in SEQ ID NO: 19 o r20; ( d) a VLa CDR1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 36-40; ( e) a VLa CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 41-44; and (f) a VLa CDR3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 45-48. The antibody or the antigen-binding fragment further comprises a variable region b specifically binding to CD47, wherein the variable region b comprises one or more amino acid sequences of (g)-(l): (g) a VHb CDR1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 21-23; (h) a VHb CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 24-28; (i) a VHb CDR3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 29-35; G) a VLb CDR1 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 36-40; (k) a VLb CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 41-44; and (1) a VLb CDR3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 45-48. The antibody or the antigen-binding fragment further comprises a heavy chain constant region a and a heavy chain constant region b, wherein the heavy chain constant region a and the heavy chain constant region b are linked to the heavy chain variable region a and the heavy chain variable region b, respectively, and the heavy chain constant region a and/or the heavy chain constant region b comprise one or more of the following amino acid mutations in which amino acid positions are Eu numbered: Y349C, S354C, T366W, T366S, L368A, Y407V, N297A, T366W and Y407V. (i) a VHb CDR3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 29-35; G) a VLb CDRl comprising an amino acid sequence set forth in any one of SEQ ID NOs: 36-40; (k) a VLb CDR2 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 41-44; and (1) a VLb CDR3 comprising an amino acid sequence set forth in any one of SEQ ID NOs: 45-48. The antibodies are used for treating undisclosed diseases (the specification just mention treating colorectal cancer - MC38 cells - xenografts). According to the claims, the number of possible antibodies that may comprise the variable chain domains of the anti-PD-L1 antibody is ~6,000, and for the anti-CD47 antibody, ~8,900. Thus, the number of bispecific antibodies possible if ~5x10 7 . Also, the specificity of the antibody is conferred by a set of 6CDRs in an organzed arrangement and not by randomly picking each CDR from a list of sequences. To represent this huge number, the Specification disclosed only BsAb-36, BsAb-46, BsAb-47, BsAb-71, BsAb-71-N297A. While the art of antibody manufacturing is relatively advanced, there is still a high level of polymorphism of immunoglobulins/antibodies. Obtaining of antibodies and, even further, bispecific antibodies, is not yet a trivial matter since each antibody needs to be painstakingly tested. Furthermore, treating undisclosed diseases adds an extra layer or uncertainty and vast experimentation with unpredictable results. Obtaining and testing the bispecific antibody as claimed instantly would necessitate an immense experimental endeavor and is submitted that such a feat represent un undue burden . Double Patenting 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. 08-35 Claim s 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-41 of copending Application No. 18/681485 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the antibodies claimed in the reference application (comprising the CDR sets of SEQ ID NOs: 1-9) have the same structure with the bispecific antibody having the CDR sets of SEQ ID NOs: 4, 14, 19, 36, 41, 45, and 21, 24 and 29, respectively. The structures being the same, the properties (potentially treating a disease) are the same . This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST. 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) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. ELLY-GERALD STOICA Primary Examiner Art Unit 1647 /Elly-Gerald Stoica/Primary Examiner, Art Unit 1647 Application/Control Number: 18/035,591 Page 2 Art Unit: 1647 Application/Control Number: 18/035,591 Page 3 Art Unit: 1647 Application/Control Number: 18/035,591 Page 4 Art Unit: 1647 Application/Control Number: 18/035,591 Page 5 Art Unit: 1647 Application/Control Number: 18/035,591 Page 6 Art Unit: 1647 Application/Control Number: 18/035,591 Page 7 Art Unit: 1647 Application/Control Number: 18/035,591 Page 8 Art Unit: 1647 Application/Control Number: 18/035,591 Page 9 Art Unit: 1647 Application/Control Number: 18/035,591 Page 10 Art Unit: 1647 Application/Control Number: 18/035,591 Page 11 Art Unit: 1647 Application/Control Number: 18/035,591 Page 12 Art Unit: 1647 Application/Control Number: 18/035,591 Page 13 Art Unit: 1647