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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/06/2026 has been entered.
Application Status
Claims 1-6, 8-10, and 14-17 are pending and examined on the merits herein.
Grounds of Rejection and Objection Withdrawn
Previous rejections of claims 1-6, 8-10, and 14-17 under 35 U.S.C. 103 are withdrawn in view of claim amendments.
Claim Interpretation
Claim 1 is drawn to a polypeptide able to elicit an immune response directed against the PD-L1 protein, “comprising” or “consisting of”. Because the transition phrases are in an alternative, the preamble of claim 1 is interpreted as “comprising”.
New Rejection Necessitated by Amendment
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-6, 8-10, and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Akahata (US 9,637,532 B2; cited in OA 08/082024) and Skwarczynski (Chem Sci, 2016, 7: 842-854; cited in OA 08/08/2024).
Regarding claims 1-6 and 8, Akahata teaches a virus-like particle comprising a virus structural protein of an alphavirus or a flavivirus, and an antigen which comprises a 10-300 amino acid fragment of human Programmed Death-Ligand 1 (PD-L1), or which comprises an amino acid sequence having at least 90% amino acid identity to said fragment of human PD-L1 (claim 1), comprising an antigen, wherein said antigen comprising a polypeptide sequence having at least 10 consecutive residues of a sequence selected from the group consisting of SEQ ID NOs: 4-6, 9-11, 14-18 and 19 (claim 17). Regarding claims 1-5, SEQ ID NO:17 of Akahata is comprised of 21 contiguous amino acid residues of the human PD-L1 protein from amino acid residues 49-70 (see alignment below). Regarding claim 6, the polypeptide comprising SEQ ID NO:17 of Akahata, contains the residues that are the same as instant SEQ ID NOs: 51-53, and these sequences are more than 10 contiguous amino acids as required by Akahata. Regarding claims 2-3, instant claimed SEQ ID NO: 51 comprises residues 55-67 of the PD-L1 protein as seen in the alignment blow, therefore SEQ ID NO: 17 of Akahata also includes the sequences as recited in claims 2-3. The virus like particle teaches the limitation of claim 8 wherein the polypeptide is linked to a carrier molecule.
PNG
media_image1.png
770
724
media_image1.png
Greyscale
Regarding claim 9, Akahata teaches an isolated nucleic acid molecule comprising a nucleotide sequence that encodes the entire virus-like particle according to claim 1 (claim 21).
Regarding claim 10, Akahata teaches a kit comprising (a) a pharmaceutical composition comprising the virus-like particle according to claim 1 (claim 18).
Regarding claims 14-16, Akahata teaches a method for treating cancer or infectious disease; producing an antibody against PD-1 or a ligand of PD-1 in a mammal; modulating an immune response; immunostimulation; inhibiting an interaction between PD-1 and a ligand of PD-1; or inhibiting a PD-1 activity, comprising administering the virus-like particle according to claim 1 (claim 20). Akahata further teaches that use of the virus structural protein and antigen particle comprises administering an effective amount of the particle or the pharmaceutical composition disclosed herein to a subject in need thereof (column 15, lines 11-36).
Regarding claim 17, Akahata teaches that examples of the cancer which may be treated include, but are not limited to, melanoma, renal cancer, prostate cancer, breast cancer, colon cancer and non-small cell lung cancer (column 15, lines 44-46).
Akahata does not teach cyclization of the peptide.
Skwarczynski teaches that there are methods to improve metabolic stability of peptide antigens including peptide cyclization (Figure 3) and that as an example, cyclization of epitopes has become a popular strategy in HIV vaccine development. Cyclisation of an epitope also restrains its three-dimensional structure and therefore might be used for the assembly of conformational epitopes (page 846, column 2, paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application apply cyclization of the peptide vaccine as taught by Skwarczynski to the PD-L1 peptide vaccine to treat cancer as taught by Akahata. The ordinary artisan would have been motivated to do so because as Skwarczynski teaches cyclization of peptide antigens improves metabolic stability and would therefore provide an improvement to the PD-L1 peptide vaccine of Akahata.
The rationale to apply a technique taught by the prior art as improving the therapeutic and production characteristics of a similar construct is to predictably obtain an improvement to the second construct and is consistent with the exemplary rationales provided by the Supreme Court in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1395-97 (2007) and discussed in M.P.E.P. § 2143. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed November 06, 2025 have been fully considered but they are not persuasive.
Applicant submits: Moreover, there is no teaching, suggestion, or motivation in Akahata to pick (i) the windows 55-67, 85-101, 138-156, or 208-223, and (ii) to present them as isolated, at-most-30-mer peptides (rather than as VLP-embedded fusion inserts) that are able to elicit a PD-LI-directed immune response.
In response: Akahata does in fact teach SEQ ID NO: 17, which contains the window 55-67 of PD-L1 as detailed in the new 103 rejection above.
Further the VLP embedded fusion insert qualifies as a carrier molecule as recited in instant claim 8. Further Akahata claims the molecules are for use in a method to treat cancer, as well as specifically “modulating an immune response; immunostimulation; inhibiting an interaction between PD-1 and a ligand of PD-1” in claim 20 as detailed above. Which would result in a polypeptide that is immunogenic specifically to PD-L1
Applicant submits: Furthermore, claim 1 requires a functional limitation: the cyclized polypeptide is "able to elicit an immune response directed against the PD-Ll protein." Akahata contains no data showing that any isolated PD-L 1 peptide (let alone the four specific windows now claimed) is immunogenic to PD-Ll. Additionally, as was previously indicated by the Examiner, "Akahata does not teach cyclization of the peptide." A generic stability-improvement rationale from Skwarczynski does not create a reasonable expectation of success that cyclizing any arbitrarily selected
PD-Ll fragment would elicit the required PD-LI-directed immune response.
In response: In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The obviousness rejection as detailed above gives motivation to cyclize the protein fragment of Akahata to improved stability.
Further, the specification of Akahata teaches that virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome, potentially yielding safer and cheaper vaccine candidates; US patent publication No. 2012/0003266 discloses a virus-like particle (VLP) comprising one or more Chikungunya virus structural proteins which is useful for formulating a vaccine or antigenic composition for Chikungunya that induces immunity, also claimed in claim 9 (background art). While US patent publication No. 2012/0003266 teaches that also included are cyclized peptides (para 0133).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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, Julie Wu can be reached at 571-272-5205. 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.
/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643