HUMAN PAPILLOMAVIRUS VACCINES AND USES OF THE SAME

§103 §112 §DP

Detailed Office 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 . 37 C.F.R. § 1.114 A request for continued examination under 37 C.F.R. § 1.114, including the fee set forth in 37 C.F.R. § 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 U.S.P.Q. 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 C.F.R. § 1.114, and the fee set forth in 37 C.F.R. § 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 C.F.R. § 1.114. Status of the Claims Claims 2, 8, 9, 12, 13, 17, 18, 24, 27, 29, 30, 32, 34-38, and 40-42 are pending in the instant application. 37 C.F.R. § 1.98 The information disclosure statement filed 01 September, 2026, has been placed in the application file and the information referred to therein has been considered. 35 U.S.C. § 112(d) The following is a quotation of 35 U.S.C. § 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claims 2, 8, 9, 12, 13, 17, 18, 24, 27, 29, and 30 are rejected under 35 U.S.C. § 112(d), as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant is reminded that a claim in dependent form should contain a reference to a previously set forth claim. The aforementioned claims do not rely upon a previously set forth claim. Applicant may cancel the claim(s), rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Joint Inventors, Common Ownership Presumed 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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed 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. Graham v. Deere Analysis The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 U.S.P.Q. 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103(a) 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. 35 U.S.C. § 103 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 of this title, 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. Claims 2, 8, 9, 12, 13, 17, 18, 24, 27, 29, 30, 32, 34, and 35-38, are rejected under 35 U.S.C. § 103 as being unpatentable over Brough et al. (U.S. Pat. No. 12,404,306 B2, issued 02 September, 2025; claiming priority to Prov. Appl. No. 62/639,354, filed 06 March, 2019; hereinafter referred to as “Brough et al. (‘306)”), in view of Zhu et al. (U.S. Pat. Appl. Pub. 2010/0158930 A1, published 24 June, 2010; hereinafter referred to as “Zhu et al. (‘930)”). The claims are directed toward methods of inducing an anti-HPV immune response (claim 32) or treating an HPV-associated disease (e.g., cancer; claim 34) comprising administering a fusion protein comprising an HPV-16 or -18 E5 peptide and an HPV-16 or -18 E6 or E7 peptide. Additional limitations require the inclusion of specific HPV epitopes (e.g., SEQ ID NOS.: 130, 113, 131, 122, and 139; claim 2) or fusion proteins (e.g., SEQ ID NOS.: 145, 51, and 243; claims 8, 12, 13, 17, and 18). The inclusion of an ankyrin-like repeat domain in the fusion protein is also contemplated (claim 9). Claims 24, 27, 29, and 30 are directed toward the expression vector employed (e.g., adenoviral vector). Finally, claims 35-38 are directed toward the treatment of specific HPV disease or disorders (e.g., cervical cancers; claims 36 and 37) and therapeutic amounts. Brough et al. (‘306) discloses the preparation of fusion proteins comprising an HPV-16 and/or -18 E5 peptide fused to and HPV-16 and/or -18 E6 or E7 peptide (see SUMMARY OF THE DISCLOSURE, ¶s [0006]-[0030]; Fig. 3; Examples 1-3). In particular, this patent discloses different HPV peptide designs that incorporate consensus HPV CTL epitopes. This teaching provides the same HPV-16 and/or -18 E5, E6, and E7 epitopes and fusion proteins claimed. Disclosed epitopes include those set forth in SEQ ID NOS.: 130, 113-121, 131-138, 122-129, and 139-147. Fusion proteins encompasses by SEQ ID NOS.: 51-53 and 243 are also described (see Examples 1-3 and Table 2). The sequences set forth in the ‘306 patent appear to be identical to those currently claimed. Fusion peptides comprising ankyrin-like repeats are also clearly set forth (see ¶s [0020] and [0276]). A detailed discussion is provided with respect to the utilization of gorilla adenoviral vectors including those deficient in E1-4 (see ¶s [0099]-[0136]). While this application clearly contemplates using these HPV fusion proteins in a vaccine to treat HPV-related disease and/or induce immune responses against HPV, it fails to provide any actual working embodiments involving the administration of an HPV vaccine to a patient. However, Zhu et al. (‘930) disclose methods for the treatment or prevention of HPV-related disease in a subject comprising administering a nucleic acid encoding an HPV-18 immunogen (see Example 7, Therapeutic and Prophylactic Vaccination of Human Subjects (Prophetic), ¶s [0177]-[0178]). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the recombinant adenoviruses encoding HPV fusion proteins, as taught by Brough et al. (‘306), to a patient for the purpose of treating HPV-related infections and cancers, as taught by Zhu et al. (‘930). One of ordinary skill in the art would have reasonably expected these HPV fusion proteins to be highly immunogenic and effective at treating various HPV-related cancers. Claims 40-42 are rejected under 35 U.S.C. § 103 as being unpatentable over Brough et al. (‘306), in view of Zhu et al. (930), as applied supra to claim 34, and further in view of Bell et al. (U.S. Pat. Appl. Pub. No. 2020/0392535 A1, published 17 December, 2020; hereinafter referred to as “Bell et al. (‘535)”). The claims further require the administration of a biological response modifier or immune checkpoint inhibitor. Bell et al. (‘535) disclose methods of treating cancer in a patient comprising administering a recombinant orthopoxvirus vector encoding a recombinant antigen and biological response modifiers (see claims 77-79, 155-157, and 183-185) and/or immune checkpoint inhibitors (see claims 64-68, 142-146, and 170-174). The inclusion of biological response modifiers and/or immune checkpoint inhibitors facilitates the development of robust immune responses against both the tumor antigen and tumor. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include both biological response modifiers and/or immune checkpoint inhibitors into the HPV vaccination method of Brough et al. (‘306) and Zhu et al. (930) to produce a strong and robust immune response against both the HPV tumor antigen and tumor itself. Nonstatutory Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 U.S.P.Q.2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 U.S.P.Q.2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 U.S.P.Q. 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 U.S.P.Q. 761 (C.C.P.A. 1982); In re Vogel, 422 F.2d 438, 164 U.S.P.Q. 619 (C.C.P.A. 1970); and In re Thorington, 418 F.2d 528, 163 U.S.P.Q. 644 (C.C.P.A. 1969). A timely filed terminal disclaimer in compliance with 37 C.F.R. § 1.321(c) or § 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See M.P.E.P. § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in M.P.E.P. § 2159. See M.P.E.P. §§ 706.02(l)(1)-706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 C.F.R. § 1.321(b). The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp. Claims 32, 34-38, 2, 8, 9, 12, 13, 17, 18, 24, 27, 29, and 30, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,404,306. Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the ‘306 patent disclose polynucleotides encoding an HPV-16 or -18 fusion protein comprising the HPV-16 or -18 E5 peptide fused to one or more HPV-16 or -18 E6 and/or E7 epitopes. The claimed fusion peptide sequences are identical to those set forth in SEQ ID NOS.: 52 or 54. Methods of vaccination using gorilla adenoviral vectors encoding these regions are also displayed. Accordingly, the claims of the ‘306 patent anticipate the claims of the instant application. Claims 40-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,404,306, in view of Bell et al. (‘535). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application further reqiore the administration of a biological response modifier or immune checkpoint inhibitor. The claims of the ‘306 patent disclose polynucleotides encoding an HPV-16 or -18 fusion protein comprising the HPV-16 or -18 E5 peptide fused to one or more HPV-16 or -18 E6 and/or E7 epitopes. The claimed fusion peptide sequences are identical to those set forth in SEQ ID NOS.: 52 or 54. Methods of vaccination using gorilla adenoviral vectors encoding these regions are also displayed. This patent does not disclose the utilization of biological response modifiers or checkpoint inhibitors. However, Bell et al. (‘535) disclose methods of treating cancer in a patient comprising administering a recombinant orthopoxvirus vector encoding a recombinant antigen and biological response modifiers (see claims 77-79, 155-157, and 183-185) and/or immune checkpoint inhibitors (see claims 64-68, 142-146, and 170-174). The inclusion of biological response modifiers and/or immune checkpoint inhibitors facilitates the development of robust immune responses against both the tumor antigen and tumor. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate these modifiers and inhibitors into the compositions and method of the ‘306 patent. Accordingly, the claims are not patentably distinct from one another. Correspondence Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600. 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. Respectfully, /JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 22 September, 2026