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 6/27/2022 wherein the specification and claims 1-9 and 17--24 were amended and claims 10-15 were canceled.
Note(s): Claims 1-9 and 16-24 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.
Note(s): The earliest effective filing date is 12/27/2019 because the pending invention is fully disclosed therein.
The Examiner acknowledges receipt of the certified copies of papers required by 37 CFR 1.55 filed 6/27/2022.
Claim Interpretation
Independent claim 1 is directed to a compound comprising a cyclic peptide having the Formula Arg-Ala-[D-Cys-Arg-(2-Nal or Phe)-(Phe or His)-(Cys or Pen) in combination with a linker, chelator, and a radioisotope.
Claim 5 is directed to a precursor compound wherein the compound lacks the radioisotope of independent claim 1.
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
Applicant's election without traverse of Group I (claims 1-4 and 8) filed 11/12/2025 is acknowledged. The restriction requirement is still deemed proper and is therefore 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. Claims 1-4 and 8 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Withdrawn Claims
Claims 5-7, 9, and 16-24 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Information Disclosure Statement
The information disclosure statement filed 6/27/2022 was considered.
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 1-4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Amodeo et al (US Patent 9,102,710) in 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 or Phe)-(Phe or His)-(Cys or Pen) in combination with a linker, chelator, and a radioisotope.
Claim 2 is directed to a linker combination comprising at least two subunits thereof.
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.
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 which comprises RACRFFC (Arg-Ala-Cys-Arg-Phe-Phe-Cys) and overlaps with a sequence encompassed by Applicant’s Formula I in independent claim 1 when X = Phe, Y = Phe, and Z = 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) Amodeo et al disclose a cyclic peptide encompassed by Applicant’s Formula I as explained supra.
(2) Amodeo et al disclose that one may have a composition comprising the compound, a linker, and radioisotope. Amodeo et al disclose various linkers that may be used with their 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 of Applicant.
In regards to linkers, both Amodeo et al and Demmer et al disclose overlapping linkers that are compatible with CXCR4 receptor binding compounds. The linkers contain some of the same functional groups present in linkers of the pending invention.
For the reasons set forth above, claims 1-4 and 8 are rendered obvious by the cited prior art. Furthermore, since both Amodeo et al and Demmer et al are directed to cyclic peptides that bind the CXCR4 receptor and may incorporate linkers and radioisotopes and are used in the treatment of CXCR4 expressing tumors/cancers, the references may be considered to be within the same field of endeavor. Thus, the reference teachings are combinable.
Comments/Notes
For clarity of Group I (pending claims 1-4 and 8), the following suggestions are respectfully made: (1) claim 1, line 3, delete ‘the following’; (2) claim 1, lines 9-11, replace ‘being’ with ‘is’; (3) claim 2, lines 6, 15, and 25, replace ‘chosen’ with ‘selected’; (4) claims 2, line 9, insert ‘or’ before ‘3-‘; line 13, insert ‘or’ before ‘6-azido-1-hexylamine’; line 18, insert ‘or’ before ‘3-‘; (5) claim 3, line 2, replace ‘chosen’ with ‘selected’; (6) claim 3, line 7, insert ‘or’ before ‘TRAP(Azide)3’; (7) claim 4, line 2, replace ‘chosen’ with ‘selected’; (8) claim 8, line 3, replace ‘association’ with ‘combination’.
Conclusion
Claims 1-4 and 8 are rejected and claims 5-7, 9, and 16-24 are withdrawn.
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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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
February 24, 2026