CTFR 17/633,912 CTFR 82605 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. Applicant’s amendment filed on 05/22/2026 is acknowledged. Claims 8-12 are pending and under consideration for their full scope. Applicant’s IDS document filed on 05/22/2026 has been considered. The following rejection is necessitated by Applicant’s amendment filed on 05/22/2026 . 07-06 AIA 15-10-15 6. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 07-20-aia AIA 7. 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. 07-21-aia AIA 8. Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Huss et al. (PTO-892 mailed on 02/25/2026; Reference U) in view of Baudino et al. (PTO-892 mailed on 02/25/2026; Reference V) and Pfender et al. (PTO-892 mailed on 02/25/2026; Reference W) . Huss et al. teaches the PC61.5.3 antibody which are 100% identical over length and sequence to instant SEQ ID NOs 1 and 2 (In particular, Table 2). Huss et al. teaches that the in vivo impact of a therapeutic monoclonal antibody is determined by both its epitope specificity (e.g. blocking or non‐blocking of ligand interactions) and heavy‐chain constant region (Fc) effector function (e.g. depleting or non‐depleting). Varying the Fc properties of an antibody can significantly affect the biological impact in vivo . The reference teaches engineering the heavy‐chain constant region of PC61 to alter Fc‐mediated effector function without changing antibody specificity. By comparing Fc variants with highly divergent effector function we are able to demonstrate in mouse models the differential effects of actively depleting CD25 + Treg cells through only blockade of CD25 signaling. Our results demonstrate that immune homeostasis can be maintained during CD25 blockade but aberrant immune activation prevails when CD25 + Treg cells are actively depleted. These results should inform the design of monoclonal antibodies that therapeutically target the high‐affinity IL‐2R. The reference teaches the construction of Fc variants of the PC61.5.3 antibody. The reference teaches the antibody daclizumab. (In particular, Table 2, supplemental materials, whole document). The claimed invention differs from the prior art in the recitation of “wherein the mutated Fc region comprises a D265A mutation” of claims 8-12; and treating transplant rejection and autoimmune diseases such as multiple sclerosis. Baudino et el teaches that “In conclusion, our present study revealed the loss of Fc-associated effector functions of IgG when aspartic acid at position 265 was substituted with alanine. Because this substitution did not affect the Ag-binding ability of IgG, the D265A variant may present an advantage for therapeutic applications in which Ab is required to bind to Ag, but must not trigger Fc-mediated effector activities.” (In particular, final paragraph, whole document). Pfender et al. teaches that Daclizumab is an anti-CD25 antibody which treats multiple sclerosis and renal transplant. (In particular, whole document). It would have been obvious to one of ordinary skill in the art at the time of invention to have used a D265A mutation in the PC61.5.3 antibody of Huss et al. because Huss et al. teaches that the in vivo impact of a therapeutic monoclonal antibody is determined by both its epitope specificity (e.g. blocking or non‐blocking of ligand interactions) and heavy‐chain constant region (Fc) effector function (e.g. depleting or non‐depleting) and that varying the Fc properties of an antibody can significantly affect the biological impact in vivo . The reference further teaches engineering the heavy‐chain constant region of PC61 to alter Fc‐mediated effector function without changing antibody specificity resulted in immune homeostasis during CD25 blockade instead of aberrant immune activation which occurs when CD25 + Treg cells are actively depleted. These results should inform the design of monoclonal antibodies that therapeutically target the high‐affinity IL‐2R. The reference teaches the construction of Fc variants of the PC61.5.3 antibody. It would have been obvious to have treated patients with renal transplants and multiple sclerosis using the antibody of the combined reference teaching because daclizumab, which is an example of an anti-CD25 antibody taught by Huss et al. has been demonstrated to treat multiple sclerosis and renal transplants as taught by Pfender et al. From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary. Applicant’s arguments filed on 05/22/2026 have been fully considered, but are not found persuasive. Applicant argues: “As an initial matter, none of the cited references teach or suggest using a PD61 antibody - let alone a PD61 antibody of SEQ ID NO: 1 and SEQ ID NO: 2 - to treat autoimmune disease or transplant rejection, to inhibit immune response, or to stimulate Tregs as is presently claimed. Furthermore, the instantly claimed PD61 antibody is shown to be surprisingly better than daclizumab, as described in paragraph [0056] of the present application: "The antibodies of the present invention inhibit IL-2 biding to a lesser extent than Basiliximab and Daclizumab. When compared with prior antibodies, the anti-CD25 antibodies of the present invention increase Tregs' suppressive function, induce activation of integrins aLp2, a4p1, and a4p7, but do not inhibit IL-2 binding or cause Tregs depletion in vivo." Specification, paragraph [0056]. Daclizumab is known to suppress Treg function, as described in Rech et al. (Sci. Transl. Med. 4, 134ra62), a copy of which is submitted herewith by way of a Supplemental Information Disclosure Statement. In contrast, PC61 has been demonstrated to increase Treg function, as shown in Fig. 2A of Sun et al. (Cell Reports 42, 112996), a copy of which is submitted herewith by way of a Supplemental Information Disclosure Statement. Advantageously, this improves the therapeutic effect of the instantly claimed PC61 antibody compared to daclizumab or other anti-CD25 antibodies, which is not appreciated by Huss, Baudino, or Pfender. Applicant also emphasizes that the instantly claimed D265A mutation is particularly beneficial for treating autoimmune diseases, which is also not disclosed or appreciated by the cited references. It is known that wildtype PC61 antibodies can worsen autoimmune diseases, such as multiple sclerosis, as described in Stephens et al. (Proc. Natl. Acad. Sci. USA 102, 17418-17423), a copy of which is submitted herewith by way of a Supplemental Information Disclosure Statement. In contrast, Fig. 7 of Sun et al. demonstrates that the instantly claimed PC61 antibody with a D265A mutation ameliorates autoimmune diseases, such as multiple sclerosis. Contrary to the assertions of the Office, even if, for the sake of argument, one of skill in the art would be motivated to use a D265A mutation described by Baudino in the PC61.5.3 antibody of Huss, it would not have been obvious to use the resulting antibody to treat autoimmune diseases, as PC61 was known in the art to worsen autoimmune diseases. There would not be a reasonable expectation of success that the instantly claimed PC61 antibody would be suitable for the claimed method. Thus, Applicant submits that the claims are not obvious.” It is the Examiner’s position that Applicant’s arguments are directed to arguing against the obviousness of treating autoimmune disease and stimulating regulatory T cells, but the arguments are not directed to the inhibition of an immune response as recited in claim 11. Since the claim is directed to the inhibition of any immune response, including IL-2 signaling, claim 11 remains obvious in view of the prior art. The rejection stands for reasons of record. 9. Claims 8-10 and 12 appear to be in condition for allowance . 07-40 AIA 10. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL . See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action. 11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (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. June 2, 2026 /Nora M Rooney/ Primary Examiner, Art Unit 1641 O S -containing polypeptide Application/Control Number: 17/633,912 Page 2 Art Unit: 1641 Application/Control Number: 17/633,912 Page 3 Art Unit: 1641 Application/Control Number: 17/633,912 Page 4 Art Unit: 1641 Application/Control Number: 17/633,912 Page 5 Art Unit: 1641 Application/Control Number: 17/633,912 Page 6 Art Unit: 1641 Application/Control Number: 17/633,912 Page 7 Art Unit: 1641
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