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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 5/27/2026 wherein claims 1-3 were amended; claims 10-15 were canceled; and claim 25.
Note(s): Claims 1-9 and 16-25 are pending.
Priority and Priority Document
This application is a 371 of PCT/EP2020/087792 filed 12/23/2020 which claims benefit to Italy IT102019000025588 filed 12/27/2019.
The Examiner acknowledges receipt of the certified copies of papers required by 37 CFR 1.55 filed 6/27/2022.
Note(s): The earliest effective filing date is 12/27/2019 because the pending invention is fully disclosed in the priority document.
Claim Interpretation
Independent claim 1 is directed to a compound comprising a cyclic peptide having the Formula Arg-Ala-[D-Cys-Arg-(2-Nal)-(His)-(Cys or Pen) in combination with a linker, chelator, and a radioisotope.
Claim 5 is directed to a precursor compound wherein the compound has the formula as set forth therein.
Claim 16 is directed to a method of obtaining a radiopharmaceutical compound as set forth therein.
Claim 17 is directed to a kit comprising the precursor compound of claim 5.
Claim 18 is directed to a method of treating a CXCR4 expressing disorder.
Claim 21 is directed to a pharmaceutical composition comprising a non-radiolabeled cyclic peptide compound.
Claim 22 is directed to a method of treating a CXCR4 expressing disorder using the composition of claim 21.
Applicant’s Election
Once again, Applicant's election without traverse of Group I (pending claims 1-4, 8, and 25) filed 11/12/2025 is acknowledged. The restriction requirement was deemed proper and made FINAL.
Applicant elected the following species for initial examination: radiopharmaceutical compound (68Ga-NOTA), peptide sequence (Arg-Ala-[D-Cys-Arg-2-Nal-His-Pen-COOH, chelator (NOTA), and linker (6-(4-aminobenzamido)hexanoic acid. Pending claims 1-4, 8, and 25 read on the elected species.
Initially, Applicant’s elected species was searched. No prior art was found to reject the specific species. As a result, the search was extended to the species cited below in the rejection. The search was not further extended because prior art was found which could be used to reject the claims.
Withdrawn Claims
Claims 5-7, 9, and 16-24 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Response to Applicant’s Amendment and/or Argument
The Applicant's arguments and/or amendment filed 5/27/2026 to the rejection of claims 1-4 and 8 made by the Examiner under 35 USC 103 have been fully considered and deemed persuasive because Applicant amended the claims to overcome the rejection. Therefore, the said rejection is hereby WITHDRAWN.
NEW GROUNDS OF REJECTION
103 Rejection
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.
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.
The factual inquiries 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.
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 as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention 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.
Claims 1, 3, 4, 8, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Maro et al (J. Med. Chem., 2017, Vol. 60, pages 9641-9652) in view of Amodeo et al (US Patent 9,102,710) and in further view of Demmer et al (WO 2011/131731).
Independent claim 1 is directed to a compound comprising a cyclic peptide having the Formula Arg-Ala-[D-Cys-Arg-(2-Nal)-(His)-(Cys or Pen) in combination with a linker, chelator, and a radioisotope.
Claim 3 is directed to various chelators including NOTA, DOTA, DTPA, NETA, TETA, and NODAGA.
Claim 4 is directed to various radioisotopes including 68Ga, 67Ga, 64Cu, 44Sc, 47Sc, 111In, 177Lu, 86Y, 90Y, 225Ac, 213Bi, 212Pb, and 18F.
Claim 8 is directed to a radiopharmaceutical composition comprising compound of claim 1 in combination with one or more excipients and/or adjuvants.
Claim 25 is directed to a radiopharmaceutical compound according to claim 2 wherein the chelator is NOTA or DOTA.
Maro et al is directed to cyclic CXCR4 antagonists useful as anticancer agents. In particular, Maro et al disclose that the sequence Ac-Arg-Ala-[D-Cys-Arg-2-Nal-Phe-Pen]-COOH (Compound 12, page 9643) was found to be effective (see entire document, especially, abstract; page 9642, right column, first complete paragraph; page 9643, Compound 12).
While Maro et al disclose that the CXCR4 peptides may be labeled with 64Cu, 18F, and 68Ga (e.g., 68Ga-pentixafor) (page 9642, left column, lines 30-37). Thus, it would have been obvious to a skilled artisan prior to Applicant’s effective filing date to radiolabel a CXCL targeting molecule.
Maro et al fail to disclose the sequence Ac-Arg-Ala-[D-Cys-Arg-2-Nal-Phe-Pen]-COOH in combination with a linker and chelator.
Amodeo et al disclose CXCR4 receptor binding compounds that are used in the treatment, and diagnosis of neoplasms (see entire document, especially, abstract; column 9, lines 38-40). While Amodeo et al disclose that the compounds may have different sequences, one cyclic peptide sequence that is exemplified is SEQ ID No. 7 that is structurally similar to that of pending claim 1. Amodeo et al’s peptide comprises RACRFFC (Arg-Ala-Cys-Arg-Phe-Phe-Cys) (see Amodeo et al, column 5, line 45).
Amodeo et al disclose that one may have linkers and radioisotopes present (column 8, lines 8-17). The linkers may be used between various peptide units (columns 6-7, bridging paragraph). Possible linkers include those comprising polyethylene glycol, diaminohexane, and hexamethylenediamine (column 7, lines 30-34; column 15, lines 51-65).
Amodeo et al disclose that one may have pharmaceutical compositions comprising one or more excipient or pharmacologically acceptable carriers (column 9, lines 63-67).
Demmer et al disclose cyclopeptide derivatives that binding to a CXCR4 receptor (see entire document, especially, abstract; page 1, lines 10-12). In addition, it is disclosed that one may have linkers between cyclic peptide subunits. Possible linkers include those having a variety of functional groups such as amino, azido amido, poly(alkylene glycols), (pages 28-29, bridging paragraph; page 29, lines 5-14; page 32, lines 3-20).
Demmer et al disclose chelators such as NOTA, DOTA, DTPA, TETA, and NODAGA (page 33, lines 4-5; page 36, lines 31-34). Also, Demmer et al disclose that a multitude of radioisotopes such as 68Ga, 67Ga, 64Cu, 47Sc, 111In, 177Lu, 86Y, 90Y, 225Ac, 213Bi, 212Pb, and 18F may be used to evaluate CXCR4 diseases/disorders such as tumors and cancers (page 36, lines 1-7; page 44, lines 7-25).
It would have been obvious to one of ordinary skill in the art prior to the effective date of the pending invention to generate a compound encompassed by Applicant’s Formula I for the following reasons.
(1) Maro et al disclose that the cyclic peptide Ac-Arg-Ala-[D-Cys-Arg-2-Nal-Phe-Pen]-COOH is a well-known and effective CXCR4 agent.
(2) Amodeo et al disclose a cyclic peptide similar to that of Maro et al is a composition comprising the compound, a linker, and radioisotope. Amodeo et al disclose various linkers that may be used with the CXCR4 compounds including 1,6-diaminohexane. The teachings of Demmer et al disclose additional linkers and radioisotopes as well as various chelators compatible with CXCR4 receptor binding compounds. Specifically, Demmer et al disclose that it is well known in the art to have chelators such as NOTA, DOTA, DTPA, TETA, and NODAGA (page 36, lines 31-34; pages 36-37, bridging paragraph) conjugated to CXCR4 receptor binding compounds. The chelators of Demmer et al overlap with those of Applicant’s invention. Also, Demmer et al disclose that a multitude of radioisotopes such as 68Ga, 67Ga, 64Cu, 47Sc, 111In, 177Lu, 86Y, 90Y, 225Ac, 213Bi, 212Pb, and 18F may be used to evaluate CXCR4 diseases/disorders (page 36, lines 1-7). The radioisotopes overlap with those suggested in both Maro et al and Demmer et al.
(3) Since Maro et al, Demmer et al, and Maro et al are all directed to CXCR4 agents that optionally incorporate linkers and/or radioisotopes, the references may all be considered to be within the same field of endeavor. Thus, the reference teachings are combinable.
For the reasons set forth above, claims 1, 3, 4, 8, and 25 are rendered obvious by the cited prior art.
Claim Objection
Claim 2 is 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.
Comments/Notes
Amodeo et al (US Patent 9,102,710) and Demmer et al (WO 2011/131731) were listed on the ‘Notice of References Cited’ (PTO-892) mailed 3/2/2026.
Conclusion
Claims 1, 3, 4, 8, and 25 are rejected; claim 2 is objected; and claims 5-7, 9, and 16-24 are withdrawn.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
August 3, 2026
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