PEPTIDES AND METHODS OF USE

Detailed Office Action Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent provisions. Status of the Claims Acknowledgement is hereby made of receipt and entry of the communication filed 31 July, 2026. Claims 2-18 are pending in the instant application. Applicant’s election of Group I (claims 2 and 5-18) without traverse is noted. Claims 3 and 4 are withdrawn from further consideration by the examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a nonelected invention. 37 C.F.R. § 1.98 The information disclosure statements filed 30 December, 2024, 02 May, 2025, and 17 February, 2026, have been placed in the application file and the information referred to therein has been considered. Applicant is remined that the listing of references in the specification is not a proper information disclosure statement. 37 C.F.R. § 1.98(b) requires a list of all patents, publications, applications, or other information submitted for consideration by the Office, and M.P.E.P. § 609.04(a), subsection I. 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. 37 C.F.R. § 1.84 Acknowledgement is hereby made of receipt and entry of the drawings filed on 25 October, 2023, which are deemed to be acceptable. Joint Inventors, Common Ownership Presumed This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. § 102(b)(2)(C) for any potential 35 U.S.C. § 102(a)(2) prior art against the later invention. 35 U.S.C. § 103 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 of this title, 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. Graham v. Deere The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claims 2 and 5-18 are rejected under 35 U.S.C. § 103 as being unpatentable over the combined teachings of Krishna and Cunnion (U.S. Pub. No. 2019/0209660 A1, published 11 July, 2019; hereinafter referred to as “Krishna and Cunnion (‘660)”) and Krishna and Cunnion (U.S. Pub. No. 2016/0376322 A1, published 29 December, 2016; hereinafter referred to “Krishna and Cunnion (‘322)”), in view of Siakavellas and Bamias (2018). The claims are directed toward a method of preventing, treating, and/or mitigating the toxicity of immune checkpoint inhibitors in a subject in need thereof comprising administering a PIC1 peptide selected from SEQ ID NO.: 2 and/or 3. The former peptide (PA-dPEG24/RLS-0071) contains a C-terminal PEG whereas the latter peptide contains a sarcosine residue (PA-I8Sar/RLS-0088). Claim 5 references the components of the pharmaceutical. Claims 6-16 are directed toward the clinical regimen followed. Claims 17 and 18 reference the concomitant administration of a checkpoint inhibitor. Krishna and Cunnion (‘660) disclose methods for the treatment of transfusion-related acute lung injury and systemic lupus erythematosus (SLE) comprising administering PIC1 peptides. Both PA-dPEG24 and PA-I8Sar were effective at treating transfusion-related acute lung injury by modulating immune complex activation of the complement system and NET formation in the subject. PIC1 also inhibited myeloperoxidase (MPO) activity in the subject. This teaching does not disclose the administration of PIC1 peptides to ameliorate the toxicity of immune checkpoint inhibitors. Krishna and Cunnion (‘322) provide PIC1 peptides for the treatment of complement-mediated inflammatory diseases and non-complemented-mediated diseases. Both PA-dPEG24 and PA-I8Sar were effective at treating complement-mediated disorders. Pharmaceutical formulations and clinical regimens were also disclosed. This teaching does not disclose the administration of PIC1 peptides to ameliorate the toxicity of immune checkpoint inhibitors. Siakavellas and Bamias (2018) teach that immune checkpoint inhibitors are monoclonal antibodies against the inhibitory, co-stimulatory molecules CTLA-4 and PD-1/PD-L1. Their administration is frequently associated with frequent and diverse immune-related adverse events such as colonic inflammation. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use PIC1 peptides, including PA-dPEG24/RLS-0071 and PA-I8Sar/RLS-0088, to treat the toxic side-effects of immune checkpoint inhibitor administration. One of ordinary skill in the art would have reasonably expected PIC1 inhibitors to be useful because the inhibit complement-mediated mechanisms of inflammation. One of ordinary skill in the art would have also been able to determine optimal dosing, since this is routine in the art, to develop the optimal clinical regimen. Correspondence Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600. Information regarding the status of an application may be obtained from the Patent Center. Status information for published applications may be obtained from the Patent Center. Status information for unpublished applications is available through the 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). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. Respectfully, /JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 29 September, 2026