COMPOUNDS AND METHODS OF USE

§103 §112

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 9/4/2026 wherein claims 1-56, 60, 62-70, 73-75, and 77 were canceled and claims 57, 58, and 61 were amended. Note(s): Claims 57-59, 61, 71, 72, 76, and 78-87 are pending. Priority and Priority Document This application is a 371 of PCT/GB2020/051442 filed 6/15/2020 which claims benefit to United Kingdom GB1908573.7 filed 6/14/2019 and United Kingdom GB2004360.0 filed 3/26/2020. Once again, the Examiner acknowledges receipt of certified copies of papers required by 37 CFR 1.55. Both priority documents were submitted on 12/13/2021. Note(s): The earliest effective filing date is 6/14/2019 because the pending invention is fully supported in United Kingdom GB1908573.7 filed 6/14/2019. Response to Applicant’s Amendment and/or Arguments The Applicant's arguments and/or amendment filed 9/4/2026 to the rejection of claims 57-61, 71, 72, 76, and 78 made by the Examiner under 35 USC 103 and/or 112 have been fully considered and deemed persuasive because Applicant amended the claims to overcome the rejections. NEW GROUNDS OF REJECTION New Matter Rejection 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. Claims 57-59, 61, 71, 72, 76, and 78 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to metabolism inhibiting group (MIG) for the N-terminus (Z1) being (C=O)RG instead of NH(C=O)RG and for the C-terminus (Z2) MIG being a primary amine instead of a primary amide. The information in the amended claim is not consistent with the application’s disclosure (see US 2022/0273830, page 2, paragraph [0038]). It was asserted in the ‘Remarks’ filed 9/4/2026 that support for the changes could be found in paragraph [0136] and [0191] of the published application. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described. While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed. 112 Second Paragraph Rejections 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. Claims 58 and 61 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. Claims 58 and 61: The claims read on the compound comprising a radioactive moiety. However, claim 57 does not require that the radioactive moiety be present. Did Applicant intend to write ‘further comprising’ instead of ‘comprises’? The use of the phrase ‘further comprising’ in claim 58 and 61 requires the presence of the radioactive moiety. In addition, the term ‘being’ should be replaced with ‘is’ as previously presented in earlier claims. 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 57-59, 61, 71, 72, 76, and 78 are rejected under 35 U.S.C. 103 as being unpatentable over Iveson et al (US Patent No 9,533,059) in view of Arbogast et al (WO 03/084574). Independent claim 57 is directed to compound of Formula I, PNG media_image1.png 121 193 media_image1.png Greyscale , wherein the variable are defined therein. cMBP is a cMet binding peptide having SEQ ID No. 7 as set forth therein. It should be noted that The variable definition of MIG, in particles as it relates to Z1 and Z2 was modified. Claims 58 and 59 are directed to alpha, beta, and/or gamma emitters. Claim 61 is directed to various radioactive moieties encompassed by claims 57 and 58 as set forth therein that includes 90Y, 177Lu, 188Re, 186Re, 67Cu, 212Bi, 213Bi, 211At, 225Ac, 131I, 166Ho, 149Pm, 199Au, 105Rh, 227Th, 153Sm, 89Sr, 223Ra, 77Br, 123I, 125I, 99mTc, 67Ga, 111In, 68Ga, 64Cu, 89Zr, 11C, 15O, 13N, 82Rb, and 18F. Claim 71 is directed to Q being MIG. Claim 72 is directed to Z1 = acetyl and Z2 = primary amide. Claim 76 is directed to a pharmaceutical composition comprising the compound of claim 57 and a biocompatible carrier. Claim 78 is directed to a pharmaceutical composition further comprising a radioactive moiety. Iveson et al is directed to peptide radiotracer compositions that are imaging agent composition and comprising radiolabeled c-Met binding peptides. The imaging agents are used for positron emission tomography (PET) imaging in vivo and managing cancer. The c-Met binding peptides are labeled with the radioisotope 18F (see entire document, especially, abstract). The compound has the formula PNG media_image2.png 26 92 media_image2.png Greyscale wherein Z1 is attached to the N-terminus of cMBP and may be MIG; Z2 is attached to the C-terminus of cMBP and may be MIG (column 3, lines 25 and 49-57). Iveson et al discloses that the metabolism inhibiting group, MIG, is at either the amino terminus (Z1) or carboxy terminus (Z2). In particular, it is disclosed that well known to those skilled in the art is for the peptide amine terminus to be NH(C=O)RG wherein RG is selected from C1-C6 alkyl, C3-C10 aryl groups, or groups that comprise polyethylene glycol (PEG). For the peptide carboxy terminus, well known groups are selected from carboxamide, tert-butyl ester, benzyl ester, cyclohexyl ester, amino alcohol, or a PEG building block (column 4, lines 44-57). Thus, based on the teaching of Iveson et al, one may have a primary amine in the Z2 position when for the amino alcohol, the nitrogen is bonded to one carbon group and two hydrogens. The skilled artisan would recognize that if the amino group in the amino alcohol is -NH2 (one carbon substituent form the alcohol chain), the compound is a primary amine in addition to being an alcohol). Thus, the limitation of the amended claim for Z2 is satisfied. In particular, Iveson et al disclose Applicant’s SEQ ID No. 7 , Ala-Gly- Ser-Cysa-Tyr-Cysc Ser-Gly-Pro-Pro-Arg-Phe-Glu-Cysd-Trp-Cysb-Tyr-Glu-Thr- Glu-Gly-Thr-Gly-Gly-Gly-Lys, in column 7, lines 16-17 which is the cMBP sequence present in independent claim 57. In column 7, lines 18-39, Iveson et al disclose that for preferred imaging agents, both Z1 and Z2 are MIG. In addition, Iveson et al disclose that Z1 is preferably acetyl (column 5, lines 19-21). which meets the limitation of Applicant’s definition of the variable Z1 in the amended claims. Iveson et al disclose that the preferred sequence is SEQ ID No: 7 with both Z1 and Z2 being MIG and attached thereto (column 10, lines 8-10), like the pending invention. In addition, it is disclosed that the Formula Z1-[cMBP]-Z2 of Iveson et al may be radiofluorinated with the group –(L)n-18F and n is zero (absent) or 1 (column 5, lines 32 and 50). When n is absent, the 18F radiolabel is bound to a chelating (complexing) moiety (column 7, lines 34-47). Thus, Applicant’s sequence (SEQ ID NO: 7), like that of the cited prior art, may have MIG attached at the (C=O)RG position at the N-terminus or at the amine of the C-terminus. A biocompatible carrier may also be present (column 10, lines 26-44). While Iveson et al disclose that one may have a chelating moiety present to conjugate to a radioactive moiety, the reference does not specifically disclose the chelators DOTAGA and DOTA. Arbogast et al is directed to multivalent constructs that are useful therapeutic and diagnostic applications (see entire document, especially, abstract). In particular, Arbogast et al is directed to cMet peptide complexes (page 8, lines 7-10), like the invention of Iveson et al. The constructs may include a chelator/chelating group. Possible chelators and chelating groups include DOTA as well as DOTA derivatives pages 8-9, bridging paragraph; pages 10-11, bridging paragraph; page 11, lines 3-10). Possible radioisotopes that may be conjugated to chelator/chelating group include 18F, 125I, 131I, 123I, 77Br, 99mTc, 67Gas, 68Ga, 111In, 90Y, 153Sm, 166Ho, 64Cu, 67Cu, 186Re, 188Re, 212Bi, 213Bi, 105Rh, 149Pm, 177Lu, and 199Au. It would have been obvious to a skilled artisan to modify the teachings of Iveson et al using Arbogast et al and generate a complex comprising a DOTA (or DOTA derivative, DOTAGA) because (1) both Iveson et al and Arbogast et al are directed to cMet peptides that may be radiolabeled and contain a chelating moiety. (2) Thus, replacing one chelator with another is obvious and within the skill of an ordinary artisan as the chelating moieties are used for overlapping groups of peptides (cMet peptides) used for diagnostic and therapeutic purposes. For the reasons set forth herein, the limitations of claims 57-59, 61, 71, 72, 76, and 78 are met. Withdrawn Claims Claims 79-87 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species. Conclusion Claims 57-59, 61, 71, 72, 76, and 78 are rejected and claims 79-87 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. 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, 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. 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. /D. L. Jones/ Primary Patent Examiner Art Unit 1618 September 28, 2026