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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 27, 2026 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 27, 2026 has been considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: “(HPV16)” in line 4 should be “(HPV18)”. Appropriate correction is required.
Claim Rejections - 35 USC § 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, 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.
Claim 1, 4, 8, 11-13, 22-24, 26, 27, and 29-32 remain rejected under 35 U.S.C. 103 as being unpatentable over Bunnik et al. (USPgPub 2017/0051019), instant SEQ ID NO: 5 alignment with Geneseq db access no AO648663 Weiner et al 2008 WO2008014521; instant SEQ ID NO: 6 alignment with Geneseq db access no AOG48664 Weiner et al 2008 WO2008014521; instant SEQ ID NO 21 with Geneseq db access no AYF71829 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO 22 with Geneseq db access no AYF71833 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO: 17 alignment with Geneseq db access no AOG48659 Weiner et al 2008 WO2008014521; instant SEQ ID NO: 19 alignment with Geneseq db access no AOG48659 Weiner et al 2008 WO2008014521; instant SEQ ID NO: 2 alignment with Geneseq db access no AO648660 Weiner et al 2008 WO2008014521; and instant SEQ ID NO: 1 alignment with Geneseq db access no AO648659 Weiner et al 2008 WO2008014521, as evidenced by Davis et al. (Clinics in Colon and Rectal Surgery. 2018 Nov; 31 (06): 368-378). All references of record.
Claims 14, 15, 18-21, 25, and 35 remain rejected under 35 U.S.C. 103 as being unpatentable over Bunnik et al., as evidenced by Davis et al., and the sequence alignments of Weiner et al. supra, as applied to claims 1, 4, 8, 11-13, 22-24, 26, 27, and 29-32 above, and further in view of instant SEQ ID NO 23 with Geneseq db access no AYF71828 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO 24 with Geneseq db access no AYF71828 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO: 10 alignment with Geneseq db access no AYF71829 Weiner et al WO2010085697; instant SEQ ID NO: 9 alignment with Geneseq db access no AYF71832 Weiner et al WO2010085697; and instant SEQ ID NO 11 with Geneseq db access no AYF71830 on Sept 2010 by Weiner et al. in WO2010085697. All references of record.
Claim 34 remains rejected under 35 U.S.C. 103 as being unpatentable over Bunnik et al., as evidenced by Davis et al., and the sequence alignments of Weiner et al. supra as applied to claims 1, 4, 8, 11-15, 18-27, 29-32, and 35 above, and further in view of instant SEQ ID NO: 7 alignment with Geneseq db access no AZL93388 by Weiner et al WO2011097640. All references of record.
Response to Arguments
On page 7 of the April 27, 2026 response to the rejection of record, applicant states that Bunnik addresses disadvantageous HPV E6/E7 polypeptides in the vaccine art by designing HPV-16, and -18, E6 and E7 proteins comprising re-ordered, partly overlapping T-cell epitopes while minimizing the number of undesired transforming neo-epitopes and so that essentially all of the epitopes are present, citing paragraphs [0015, 0053, 0055, 0442, and 0443] of Bunnik. Applicant contends that one skilled would not have sought to substitute the sequences of Weiner ‘521 (and Weiner ‘697, or Weiner ‘640) for those of Bunnik because doing so would have run the risk of re-introducing the very disadvantages that Bunnik set out to avoid: removal of important T-cell epitopes from and/or introducing new undesired T-cell epitopes into the proteins, leading to an undesired immune response, citing paragraph [0012]. Applicant points to paragraph [0518] of Bunnik, as support for warning against substitution of the HPV16 and HPV18 constructs taught, stating that “[t]he observed differences between seemingly highly similar molecules in a biologic model system demonstrate that such molecules cannot be considered mere alternatives that could be substituted for each other. This underscores the uniqueness of the designer molecules of the disclosure, and the unpredictability of the field.”
Applicant’s arguments and a review of Bunnik and Weiner ‘521 have been fully considered, but are found unpersuasive. On page 7 of the April 27, 2026 response, applicant points to Figure 23 and Example 3, beginning on page 84 of Weiner ‘521, which depicts and discusses deletions or mutations in the E6 sequence which are important for p53 binding and degradation, and mutations in the Rb binding site on the E7 protein. Therefore, the constructs of Weiner ‘521 do not comprise “undesired T-cell epitopes”, cautioned by Bunnik in paragraph [0012]. In the sequence alignments of Weiner ‘521, which all share 100% sequence identity with those sequences instantly claimed, the HPV E6/E7immunogens elicit stronger and broader cellular immune responses compared to corresponding optimized antigens, see the description provided with the alignments for instant SEQ ID NOs: 1, 2, 5, 6, 17, and 19, for improved HPV vaccines, see the description provided with the alignments for instant SEQ ID NOs: 9, 10, and 21-24. Therefore, the specific HPV-16, -18, E6 and E7 sequences of Weiner ‘521, (‘697, and ‘640) maintain “important T-cell epitopes”, identified by Bunnik as necessary features in paragraph [0012].
Regarding paragraph [0518] of Bunnik pointed to by applicant, the warning against substitution is discussing construct ‘HPV18DC2’ (paragraph [0514]) and “an alternative HPV16 designer construct” (paragraph [0517]). From paragraph [0514], these constructs only differ from the re-ordered, partly overlapping T-cell epitope designer constructs, ‘HPV18 E6E7SH’ and ‘HPV18 E6E7SH’ of Examples 2 and 8, respectively, by “exact amino acid sequence”. As evidenced by the teachings of Bunnik, ‘HPV18DC2’ of paragraph [0514] and “an alternative HPV16 designer construct” of paragraph [0517] do not maintain “important T-cell epitopes” and do not comprise “undesired T-cell epitopes”, as required by Bunnik, since both of these constructs reduce tumor suppressor activities of p53 and Rb, resulting in immortalization of primary keratinocytes. In contrast, the specific HPV-16, -18, E6 and E7 sequences of Weiner ‘521, (‘697, and ‘640) do not comprise “undesired T-cell epitopes” and the constructs maintain “important T-cell epitopes”, required by Bunnik, since the HPV-16, -18, E6 and E7 proteins of Weiner ‘521, (‘697, and ‘640) elicit stronger and broader cellular immune responses compared to corresponding optimized antigens, see the description provided with the alignments for instant SEQ ID NOs: 1, 2, 5, 6, 17, and 19, for improved HPV vaccines, see the description provided with the alignments for instant SEQ ID NOs: 9, 10, and 21-24. The HPV-16, -18, E6 and E7 proteins of Weiner all share 100% sequence identity with those sequences instantly claimed. Structure is inseparable from function.
Bunnik specifically teaches combining the HPV16- and HPV-18 E6/E7 fusion protein constructs with additional therapeutic vaccines against both HPV16 and HPV18 in the following paragraphs:
[0015] Provided is molecules that can be used in therapeutic vaccines against either HPV16 or HPV18. Such molecules can also be combined in therapeutic vaccines against both HPV16 and HPV18.
[0061] It can be used for subjects that are infected with HPV16 or HPV18, respectively. It may in certain embodiments also suitably be combined with vaccines against other HPV types. In certain embodiments, this combination is with a vaccine against HPV of a high risk type as identified above, e.g. a vaccine against HPV16 with a vaccine against HPV18. In other embodiments, the vaccine of the invention is combined with a vaccine against one or more of HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -68, -73, or -82. Such combinations could for instance be used if the exact type of HPV infection is not yet certain, or if an immune response with a prophylactic effect is desired against more than one HPV type. Also combinations of the vaccines of the invention with vaccines against HPV types that cause genital warts, such as HPV6 and/or HPV11, are envisaged. Sequences of these HPV types and the proteins encoded thereby (e.g. E6, E7, E2) are available to the skilled person in public databases…
[0449] The HPV16 E6E7SH fusion protein sequence can be combined with sequences of other HPV16 early proteins to target individuals with persistent infection and to broaden the immune repertoire in an immunized individual.
[0500] The HPV18 E6E7SH fusion protein sequence can be combined with sequences of other HPV18 early proteins to target individuals with persistent infection and to broaden the immune repertoire in an immunized individual.
In addition, the vaccine, method of inducing an immune response, and the method for treating a subject for persistent HPV infection, vulvar intraepithelial neoplasia (VIN), cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VaIN), anal intraepithelial neoplasia (AIN), cervical cancer (such as cervical squamous cell carcinoma (SCC), oropharyngeal cancer, penile cancer, vaginal cancer and/or anal cancer, of Bunnik in claims 14-23 is accomplished by administering compositions comprising recited materials.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have administered the HPV16- and HPV18- E6/E7 fusion proteins of Weiner in combination with the HPV16- and HPV18- E6/E7 fusion proteins of Bunnik to combine therapeutic efficacy against HPV16 and HPV18. MPEP § 2144.06 recites the conclusions of In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA), “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose...[T]he idea of combining them flows logically from their having been individually taught in the prior art.”
One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success for combining the HPV16- and HPV18- E6/E7 fusion proteins of Weiner in combination with the HPV16- and HPV18- E6/E7 fusion proteins of Bunnik because Bunnik explicitly teach combining the HPV16- and HPV-18 E6/E7 fusion protein constructs with additional therapeutic vaccines against both HPV16 and HPV18 in paragraphs [0015, 0061, 0449, and 0500] and the HPV16- and HPV18- E6/E7 fusion proteins of Bunnik and Weiner elicit stronger and broader cellular immune responses for therapeutic efficacy, see paragraph [0071] and Examples 3-5 and 9-12 of Bunnik and the description in the sequence alignments provided by Weiner et al.
A combination, or a substitution of one element for another known in the field to have the same function, is evidence that the claimed invention may be found obvious. See e.g., KSR International V. Teleflex Inc., 82 U.S.P.Q.2d 1385, at 1395.
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 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 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 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 MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. 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 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 8, 11-15, 18-27, and 29-32 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 9, 15, 16, 19-21, and 23-25 of copending Application No. 17,221,032 (reference application), SEQ ID NO: 5 alignment with Geneseq db access no AO648663 Weiner et al 2008 WO2008014521; instant SEQ ID NO: 6 alignment with Geneseq db access no AOG48664 Weiner et al 2008 WO2008014521; instant SEQ ID NO: 17 alignment with Geneseq db access no AOG48659 Weiner et al 2008 WO2008014521; instant SEQ ID NO: 19 alignment with Geneseq db access no AOG48659 Weiner et al 2008 WO2008014521, SEQ ID NO 21 with Geneseq db access no AYF71829 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO 22 with Geneseq db access no AYF71833 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO 23 with Geneseq db access no AYF71828 on Sept 2010 by Weiner et al. in WO2010085697; instant SEQ ID NO 24 with Geneseq db access no AYF71828 on Sept 2010 by Weiner et al. in WO2010085697 as evidenced by Davis et al. (Clinics in Colon and Rectal Surgery. 2018 Nov; 31 (06): 368-378). All references of record.
Claim 34 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 9, 15, 16, 19-21, and 23-25 of copending Application No. 17,221,032 (reference application) in view of instant SEQ ID NO: 7 alignment with Geneseq db access no AZL93388 by Weiner et al WO2011097640. All references of record.
Claim 35 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 9, 15, 16, 19-21, and 23-25 of copending Application No. 17,221,032 (reference application) in view of Geneseq db access no AYF71830 by Weiner et al. shares 100% identity with instant SEQ ID NO: 11. All references of record.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
In response to the rejection of record, applicant points out that anal or anal/perianal region is a distinct anatomical region from the vulvar region. A subject having an anal or anal/perianal intraepithelial lesion would not necessarily have a vulvar intraepithelial lesion, and vice versa.
Applicant’s arguments have been fully considered, but are found unpersuasive. Davis specifically teaches (Under “Taxonomy”):
The Lower Anogenital Squamous Terminology (LAST) project… unified terminology across all lower anogenital sites. For intraepithelial lesions, a two-tiered terminology-low or high (low-grade intraepithelial lesion [LSIL] and high-grade intraepithelial lesion [HSIL]) —reflects the biology of transient, productive HPV infections and persistent precancerous lesions.
Therefore, high-grade intraepithelial lesion, HSIL characterizing both pathologies in ‘032 and the instant claims pertains to the shared “biology of transient, productive HPV infections and persistent precancerous lesions”. Davis concludes, “The previously employed cervical intraepithelial neoplasia (CIN) or anal intraepithelial neoplasia (AIN) 1, 2, and 3 is abandoned in favor of this simpler classification.” Clearly, the current classification described by Davis pertains to histological pathology. The HSIL treated in the instant claims and the claims of ‘032 are identically characterized as high grade squamous intraepithelial lesions.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
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/Shanon A. Foley/Primary Examiner, Art Unit 1671
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