DETAILED ACTION
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 .
Status of the Application
The election and amendment of 10 November 2025 are entered.
Claims 1-19 have been canceled. Claims 20-39 are pending. Claims 20, 27, 29, 30, 38, and 39 are withdrawn without traverse. Claims 21-26, 28, and 31-37 are being examined on the merits.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 21-37) and the species of SEQ ID NO: 54 for both peptides, NPEG4 as the linker, and myristic acid in the reply filed on 10 November 2025 is acknowledged.
Claims 20, 27, 29, 30, 38, and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 November 2025.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See p.5-8, 13-14, 22-23, 35-36, 46-62, 64-68, and 70.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figures 1, 3, 4, 6-10, and 14.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 103
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 21-26, 28, and 31-37 are rejected under 35 U.S.C. 103 as being unpatentable over Turner et al. (Neuropharmacology 164:107901, published 1 March 2020, hereafter referred to as Turner) and Strømgaard et al. (WO 2015/078477 A1, published 4 June 2015, hereafter referred to as ‘477).
The Turner art discloses a PICK1 inhibitor targeting PDZ motifs in other proteins (see e.g. Introduction). In particular a compound TAT-P4-(DATC5)2 was produced, having the structure
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(see e.g. Figure 1). This constitutes a first and second peptide reading upon SEQ ID NO: 1, a linker comprising an NPEG, and a TAT peptide.
The difference between Turner and the claimed invention is that Turner does not disclose or suggest a micelle comprising first and second peptides, a linker linking the first peptide to the second peptide, and a lipophilic aliphatic group.
The ‘477 application discloses a dimeric ligand targeting PDZ domains linked by a NPEG linker (see e.g. p.3-4). The ‘477 art discloses utilizing fatty acids to extend in vitro plasma half-lives as compared to those compounds without fatty acids attached (see e.g. p.3 lines 29-33). This results in a generic structure similar to that found in Turner:
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but differing in use of a fatty acid instead of TAT. The linker L1 can be NPEG, and L2 can be a γ-Glu (see e.g. claims 6 and 7). The fatty acid moiety includes myristic acid (see e.g. claims 29 and 30). ‘477 also compares to ligands that are essentially the same in structure but either lack a fatty acid, i.e. are merely linked peptides, or contain linked peptides also linked to a TAT (see e.g. Example 3, Figure 1).
Turner does not explicitly mention micelle formation, but this is generally an inherent property of lipophilic fatty acids as they naturally self-assemble to shield the fatty acid chain from water exposure. For evidence, see e.g. Wang et al. RSC Adv. 7:41561-41572.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that since both Turner and the ‘477 art are directed to PDZ-binding short peptides linked by a NPEG linker, the fatty acid portion of ‘477 could have been readily substituted for the TAT of Turner and in doing so arrive at the claimed micelle comprising a PICK1 inhibitor. The rationale comes from the common PDZ domain targeting strategy of both ‘477 and Turner utilizing a NPEG linker, with one of ordinary skill seeking to utilize the strategy of ‘477 to extend plasma half-life as opposed to cell penetration as in Turner. Furthermore, ‘477 directly shows alteration of PDZ-targeting linked peptides having a TAT to those having various length linked fatty acids. There would have been a reasonable expectation of success because the skilled artisan would merely have had to replace a TAT peptide with the fatty acid of ‘477 and had a clear rationale to do so in order to extend plasma half-life, and the two references were otherwise directed to similar material in the form of PDZ-targeting linked peptide dimers. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claims 21-23, Turner discloses HWLKV.
With respect to claims 24-26, both Turner and ‘477 disclose and overlapping NPEG linker.
With respect to claims 28 and 31-33, as set forth above ‘477 discloses myristic acid as an option.
With respect to claim 34, the ‘477 art discloses that a linker can be one of γ-Glu, GABA, 5-Ava, proteinogenic amino acids, and nonproteinogenic amino acids. Given the limited options for proteinogenic amino acids and the claim to γ-Glu, one of ordinary skill in the art would have arrived at another acidic amino acid in the form of Asp to utilize as a linker, especially since it offers a reactive carboxylic acid group to allow for pairing to the lipophilic aliphatic group already present in ‘477.
With respect to claim 35, Turner suggests using TAMRA to monitor their peptide (see e.g. Section 2.10).
With respect to claim 36, the combination of Turner and ‘477 results in a compound overlapping with Formula (I).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658