CTNF 18/359,562 CTNF 77145 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 1. 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 08-25-01 AIA 2. Applicant’s election without traverse of Group I (claims 43-46, 50, 53, 57, 60, 63-67 and 69-76 and species (cancer): colorectal cancer in the reply filed on March 13, 2026 is acknowledged. Upon reconsideration the species election amongst the species of cancer set forth in the Election/Restriction Requirement mailed January 13, 2026, page 5, segment 5 has been withdrawn. Hence, all cancers listed in the claims are examined on the merits. 3. Claims 43-46, 50, 53, 57, 60, 63-67 and 69-76 are pending. Claim 76, drawn to a non-elected species is not examined on the merits. Claims 1-42, 47-79, 51, 52, 58, 59, 61, 62, 68 and 77-95 have been cancelled. Claims 50, 57, 69 and 73 have been amended. Claims 43-46, 50, 53, 57, 60, 63-67 and 69-75 are examined on the merits. Claim Objections 4. Claims 43 and 74 are objected to because of the following informality: it does not cite the word “and” after the semicolon on line 6 and line 5, respectively to bridge parts (i) and (ii) of the claim. Correction is required. Claim Rejections - 35 USC § 112 07-30-01 AIA 5. 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 AIA 6. Claim s 43-46, 50, 53, 57, 60, 63-67 and 69-76 are 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. 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 43 is drawn to a method comprising contacting an endogenous internalizing receptor and the target protein on the surface of a target cell with a binding agent, wherein the binding agent comprises: (i) a first binding domain that specifically binds to an endogenous internalizing receptor, wherein the endogenous internalizing receptor comprises Nectin-4; and (ii) a second binding domain that specifically binds to the target protein, wherein the target protein comprises CUB domain containing protein 1 (CDCP1). Claim 74 is drawn to a method for treating cancer comprising administering to a subject a binding agent, wherein the binding agent comprises: (i) a first binding domain that specifically binds to an endogenous internalizing receptor, wherein the endogenous internalizing receptor comprises Nectin-4; and (ii) a second binding domain that specifically binds to the target protein, wherein the target protein comprises CDCP1. Moreover, dependent claims 50, 53, 57 and 60 read on the first binding domain variable heavy chain comprising at least 80% to SEQ ID NO: 57, the first binding domain variable light chain comprising at least 80% to SEQ ID NO: 58, the second binding domain variable heavy chain comprising at least 80% to SEQ ID NO: 59 and the second binding domain variable heavy chain comprising at least 80% to SEQ ID NO: 60, respectively. The breadth of the instant claims encompasses binding agents, which read on a bispecific antibody with alterations in the CDRs. Therefore, the following grounds of rejection have been set forth. It is noted that the specification discloses table 3 shows heavy chains and light chains paired for bispecific binding, see pages 47-51 within the Substitute Specification (Clean) submitted November 27, 2023. One skilled in the art appreciates that traditional antibodies comprise two polypeptides, the so-called light and heavy chains. The antigen-combining site of an antibody is a three-dimensional structure that fully comprises six CDRs, three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of the antibody’s antigen-binding specificity. Antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of VHs and VLs do not describe the particularly identifying structural feature of the antibody that correlates with the antibody’s ability to bind the target antigen or target epitope. Absent a description of the at least minimal structural features correlating with a functional ability to bind antigen which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish the one or more CDRs which should be combined such that a resultant antigen-binding domain is capable of binding antigen, as well as degrading a target protein on a surface of a target cell and treating cancer. Although screening techniques can be used to isolate VH and VL sequences that combine to form an antigen-binding domain capable of binding antigen, 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.” It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA 79: 1979-1983, March 1982). Rudikoff teaches the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum et al. (J. Mol. Biol. 262: 732-745, 1996) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right col) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col.). De Pascalis et al. (The Journal of Immunology 169: 3076-3084, 2022) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site, see page 3079, right col. Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs , see page 3080, left col. The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (BBRC 307:198-205, 2003). Casset constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs, see entire document. Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process , see page 199, left col. and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3, see page 202, left col. Vajdos et al. (J. Mol. Biol. 320, 415-428, 2002), additionally state that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen, see page 416, left col. Chen et al. (J. Mol. Bio. 293: 865-881, 1999) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3, see page 866. Wu et al. (J. Mol. Biol. 294: 151-162, 1999) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.) but certain residues have been identified as important for maintaining conformation. Padlan et al. (PNAS 86:5938-5942, August 1989) described the crystal structure of an antibody-lysozyme complex where all 6 CDRs contribute at least one residue to binding and one residue in the framework is also in contact with antigen. Lastly, Lamminmaki et al. (JBC 276(39):36687-36694, 2001) describe the crystal structure of an anti-estradiol antibody in complex with estradiol where, although CDR3 of VH plays a prominent roll, all CDRs in the light chain make direct contact with antigen (even CDR2 of VL, which is rarely directly involved in hapten binding). Thus, the state of the art recognized that it would be highly unpredictable that an antibody comprising less than all six CDRs from both the VH and VL regions with a desired specificity would bind the same antigen. Thus, the minimal structure which provides the function of binding appears to include six CDRs (three in the heavy chain variable region and three in the light chain variable region) from the same antibody. Unless all six CDRs for each binding domain (Nectin-4 x CDCP1) are present to successfully degrade the target protein and treating cancer, the instant claims are not able to perform the claimed functions. 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. Applicant is invited to amend the claims so that they require all six CDRs from each of the listed antibodies. Applicant is invited to amend the claims to recite 6 CDRs for each binding domain targeting Nectin-4 and 6 CDRs for targeting CDCPI or 100% identity to both VH/VL for each binding domain (SEQ ID NOs: 57-60) to obviate this rejection . 07-30-02 AIA 7. 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 8. Claims 66 and 67 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. a. Claim 66 recites “a solid tumor, e.g., bladder cancer.” Bridging lines 1 and 2. This abbreviation means “exempli gratia” and in English, “for example”. This exemplary language is confusing because it reads on examples and preferences within a more general category and does not limit the scope of the claims. Accordingly, the metes and bounds cannot be determined. 9. Claim 67 recites the limitation "the bispecific binding agent" on line 2. There is insufficient antecedent basis for this limitation in the claim. 10. Claim 70 recites the limitation "the cancer therapeutic agent" on line 1. There is insufficient antecedent basis for this limitation in the claim. Conclusion 07-96 AIA 11. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure : - Chopra et al. Theranostic targeting of CUB Domain-Containing Protein 1 (CDCP1) in Multiple Subtypes of Bladder Cancer. Clinical Cancer Research 29(7): 1232-1242, April 1, 2023; and - Chopra et al. CUB domain containing protein 1 is a target for radioligand therapy in multiple bladder cancer subtypes, including Nectin-4 and TROP2 null disease. Journal of Nuclear, 63 (supplement 2) 2563; Published online August 8, 2022. 12. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule , however she can generally be reached 8AM-8PM, Monday through Friday. 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, Julie Wu can be reached on 571-272-5205. 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. ALANA HARRIS DENT Primary Examiner Art Unit 1643 20 May 2026 /Alana Harris Dent/Primary Examiner, Art Unit 1643 Application/Control Number: 18/359,562 Page 2 Art Unit: 1643 Application/Control Number: 18/359,562 Page 3 Art Unit: 1643 Application/Control Number: 18/359,562 Page 4 Art Unit: 1643 Application/Control Number: 18/359,562 Page 5 Art Unit: 1643 Application/Control Number: 18/359,562 Page 6 Art Unit: 1643 Application/Control Number: 18/359,562 Page 7 Art Unit: 1643 Application/Control Number: 18/359,562 Page 8 Art Unit: 1643 Application/Control Number: 18/359,562 Page 9 Art Unit: 1643 Application/Control Number: 18/359,562 Page 10 Art Unit: 1643 Application/Control Number: 18/359,562 Page 11 Art Unit: 1643 Application/Control Number: 18/359,562 Page 12 Art Unit: 1643
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