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 8/13/2026 wherein claims 1, 15, were amended and claims 2, 3, 6, 16-18, 20, 24-26, 28-36, 38-45, and 47-49 were canceled. In addition, the Examiner acknowledges receipt of the amendment filed 3/20/2023 wherein the claims and specification were amended.
Note(s): Claims 1, 4, 5, 7-15, 19, 21-23, 27, 37, and 46 are pending.
Priority
This application is a 371 of PCT/US2021/051322 filed 9/21/2021;
PCT/US2021/051322 claims benefit to PRO 63/242,315 filed 9/9/2021; and PCT/US2021/051322 claims benefit to PRO 63/081,632 filed 9/22/2020.
Note(s): The earliest effective filing date is 9/22/2020 because the pending invention is fully disclosed in provisional application 63/081,632.
Claim Interpretation
Independent claim 1 is directed to a compound or pharmaceutically acceptable salt thereof comprising a pH insertion peptide (pHLIP) wherein the pHLIP is selected for SEQ ID NOs: 1-8 and 239 and X1 is covalently attached to a heteroatom side chain of an amino acid residue of the pHLIP and wherein the amino acid residue is from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 residues from the C-terminus or the N-terminus, wherein X1 is Formula (I), Formula (II), or Formula (III)
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372
418
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;
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480
425
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; or
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445
434
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and all other variables are as defined in independent claim 1.
Applicant’s Election
Once again, Applicant's election without traverse of Group I (pending claims 1, 4, 5, 7-15, 19, 21-23, and 46) filed 3/13/2026 is acknowledged. The restriction requirement was deemed proper and made FINAL.
Once again, Applicant elected the species wherein X1 is Formula I,
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372
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, and pHLIP is [89Zr]Zr-DFO-cys-Var3pHLIP, thus, the compound is (D-Ala)-(D-Cys[X1])-(D-Asp)-(D-Asp)-(D-Gln)-(D-Asn)-(D- Pro)-(D-Trp)-(D-Arg)-(D-Ala)-(D-Tyr)-(D-Leu)-(D-Asp)-(D-Leu)-(D-Leu)- (D-Phe)-(D-Pro)-(D-Thr)-(D-Asp)-(D-Thr)-(D-Leu)-(D-Leu)-(D-Leu)-(D- Asp)-(D-Leu)-(D-Leu)-(D-Trp) (SEQ ID NO. 9);
Z1, Z2, and Z3 are each hydrogen; W1 is
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115
194
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; and n is 2; M1 is 89Zr4+. The diseased tissue of interest is tumor tissue.
Applicant’s elected species was searched and no prior art was found to reject the claims. The full scope of Group I was searched.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 8/13/2026 to the rejection of claims 1-15, 19, 21-23, and 46 made by the Examiner under 35 USC 112 first and second paragraphs have been fully considered and deemed persuasive because Applicant amended the claims to overcome the rejections. Therefore, the said rejections are hereby WITHDRAWN.
NEW GROUNDS OF REJECTIONS
102 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.
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bhatia et al (US 2020/0232986).
Independent claim 1 is directed to a pHLIP peptide of SEQ ID NOs: 1-8 and 239 linked to X1 wherein X1 is 0-10 residues.
Note(s): The claim is interpreted as when X1 = zero residues, then the variable X1 is absent. Thus, the claim would then only require the presents of the pHLIP peptide.
Claim 21 is directed to a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
Bhatia et al is directed t sensors for detecting and imaging cancer metastasis (see entire document, especially, abstract). In particular, in Table 4 on page 13, Bhatia et al disclose SEQ ID NO: 17 which is identical to Applicant’s SEQ ID NO: 1. In one embodiment, the tumor targeting agent comprises a detectable marker and a tumor insertion agent (pHLIP peptide) (page 13, paragraph [0105]; page 29, claims 1, 2, 5-9, and 12). Thus, the limitations of claims 1 and 21 are encompassed by the teachings of Bhatia et al.
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, 21, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Bhatia et al (US 2020/0232986) in view of Chen et al (US 2016/0213790).
Independent claim 1 is directed to a pHLIP peptide of SEQ ID NOs: 1-8 and 239 linked to X1 wherein X1 is 0-10 residues.
Note(s): The claim is interpreted as when X1 = zero residues, then the variable X1 is absent. Thus, the claim would then only require the presents of the pHLIP peptide.
Claim 21 is directed to a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
The limitations of claims 1 and 21 are met as detailed supra (see the 102 Rejection).
Bhatia et al fail to disclose a kit comprising the compound of claim 1 and kit instructions.
Claim 46 is directed to a kit comprising a pHLIP peptide and optionally X1 and instructions for the use of said kit.
Chen et al is made of record to illustrate that it is well known in the art to have pH sensitive peptides (e.g., pHLIP) that are present in kit form (see entire document, especially, abstract; page 1, paragraph [0004]). The kit comprises a biologically active substance (pHLIP compound), (page 2, paragraph [0022]; page 6, paragraph [0062]). Thus, based on the teachings of Chen et al in combination with those of Bhatia et al, it would have been obvious to one of ordinary skill in the art prior to Applicant effective filing date to generate a composition comprising a pHLIP peptide and a kit containing the active substance. In addition, it would be inherent to have instructions that detail how the kit is used and the components thereof.
Claim Objections
Claims 4, 5, 7-15, 19, 22, 23, 27, and 37 are 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
It should be noted that no prior art is cited against the pending invention for when X1 is 1-10 (see independent claim 1). Prior art is of record for when X1 is zero for SEQ ID NO: 1. The closest art is Applicant’s own work which is present in WO 2018/023098. Specifically, the pending invention is distinguished over WO 2018/023098 because the document neither teachers nor renders obvious X1 values (Formula I, Formula II, or Formula III) in combination with a pH insertion peptide (pHLIP) as set forth in independent claim 1.
Similarly, Bhatia et al (WO 2020/150560 and US Patent No. 11,835,522) disclose compounds and derivatives thereof that overlap with the pending invention like Applicant’s own work (WO 2018/023098). In addition, like WO 2018/023098, Bhatia et al neither teaches nor renders obvious X1 values (Formula I, Formula II, or Formula III) in combination with the pH insertion peptides.
Withdrawn Claims
Claims 27 and 37 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Conclusion
Claims 1, 21, and 46 are rejected; claims 27 and 37 are withdrawn; and claims 4, 5, 7-15, 19, 22, and 23 are objected.
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.
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.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
September 17, 2026
