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 .
Claim Status
Applicant’s amendments received 09JUL2026 are acknowledged.
Claims 1-15, 17, 26, and 29 have been canceled.
Claim 16 has been amended.
Claims 16, 18-25, 27-28, and 30 are pending in the instant application (i.e., Claim(s) 16 is/are independent).
Claims 24 and 30 remain withdrawn.
Claims 16, 18-23, 25, and 27-28 are examined on the merits.
Priority
The present application is a 371 National Stage of PCT International Application No. PCT/EP2020/061477, filed 24APR2020, which claims foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of EPO Application No. 19171323.9 filed on 26APR2019 has been received and is acknowledged.
Withdrawn Rejections
35 USC §103
Applicant’s arguments, see p 4-8, 35 USC §103 section, filed 09JUL2026, with respect to the rejection(s) of claim(s) 16-23 and 25-29 (i.e., rejection of claim(s) 17, 26, and 29 are moot because claims have been cancelled) under 35 USC §103 have been fully considered and said rejections of claim(s) 16, 18-23, 25, and 27-28 have been withdrawn in view of the claim amendments which add limitations not taught in the cited art filed as part of said response.
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.
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 16, 18-23, 25, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0175727 A1 (Huang, et al., effectively filed 19FEB2019), herein referred to as “’727” and in view of Bialkowski, et al., (Sci Rep, 2016, 6, 1-15), herein referred to as “Bialkowski” and Pardi, et al., (Nat Rev, 2018, 17, 261-279), herein referred to as “Pardi.”
‘727 teaches immunomodulatory therapeutic compositions of mRNA encoding an activating oncogene mutation peptide (i.e., HPV E6/E7) and an mRNA encoding a polypeptide that enhances immune responses (i.e., immunostimulatory proteins) to the activating oncogene mutation peptide (see entire document, specifically see abstract and ¶0264). Specifically, 727 teaches that all mRNAs comprise a 5’ Cap-1 structure and at least one modified nucleoside selected from N1-methylpseudouridine or are fully modified with N1-methypseudouridine (¶0105). Furthermore, the mRNA may be delivered to the subject in the form of a carrier such as a lipid nanoparticle (¶0270). ‘727 highlights that there exists a need in the art for additional effective agents that enhance immune responses to an antigen of interest (¶0005).
However, they do not teach: wherein the mRNA encoding the immunostimulatory proteins comprises CD40L, CD70, and caTLR4.
Nevertheless, Bialkowski teaches the E7-TriMix mRNA vaccine comprising mRNA encoding for immune-stimulating signals: CD40 Ligand (CD40L), constitutively active Toll-like receptor 4 (caTLR4) and CD70, collectively called TriMix and mRNA encoding the HPV16-E7 oncoprotein for inducing CD8 T cell responses that inhibit the growth of mucosally located tumours (see abstract and p 2, first and second full paragraphs).
The teachings of ‘727 and Bialkowski are further supported by the teachings of Pardi, which discloses mRNA vaccine platforms which have high potency, capacity for rapid development, and potential for low-cost manufacturing, and safe administration for widespread therapeutic use (see entire document, specifically see abstract). Furthermore, Pardi teaches that in vitro transcribed mRNA products should optimally contain an open reading frame that encodes the protein of interest, flanking UTRs, a 5’ cap and a poly(A) tail so that the mRNA is engineered to resemble fully processed mature mRNA molecules (see p 262, col 1, ¶2). With regard to the 5’ cap structure, Pardi teaches that synthetic 5’ cap analogues stabilize mRNA and increase protein translation (see box 1). Furthermore, Pardi teaches that TriMix augmented the immunogenicity of naked, unmodified, unpurified mRNA in multiple cancer vaccine studies (p 264, bottom of col 1 and top of col 2). Additionally, Pardi teaches that the mRNA field has benefited from the substantial investment in in vivo small interfering RNA administration, where lipid nanoparticles have been used for over a decade, with lipid nanoparticles becoming one of the most appealing and commonly used mRNA delivery tools (p 266, col 2, lines 14-19 of the cationic lipid and polymer-based delivery section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the immunomodulatory therapeutic compositions of mRNA encoding an activating oncogene mutation peptide (i.e., HPV E6/E7) and an mRNA encoding a polypeptide that enhances immune responses (i.e., immunostimulatory proteins) to the activating oncogene mutation peptide, wherein the mRNAs comprised a 5’ cap 1 structure and were formulated in a lipid nanoparticle disclosed by ‘727 by utilizing alternate mRNAs encoding the immunostimulatory proteins of CD40 Ligand (CD40L), constitutively active Toll-like receptor 4 (caTLR4) and CD70 as well as mRNA encoding HPV16-E7, disclosed by Bialkowski because trimix induces CD8 T cell responses that inhibit the growth of mucosally located tumours and utilization of a 5’ cap for all mRNAs provides for optimal translation and stability and that lipid nanoparticles are becoming one of the most appealing and commonly used mRNA delivery tools for mRNA-based vaccines is further supported by Pardi. One would have been motivated to do so, given the teachings of ‘727 that there exists a need in the art for additional effective agents that enhance immune responses to an antigen of interest. There would have been a reasonable expectation of success, given the knowledge that utilization of trimix combined with HPV16-E7, wherein all mRNAs comprise a 5’ Cap 1 structure and are formulated in lipid nanoparticles would provide mRNA vaccine platforms which have high potency, capacity for rapid development, and potential for low-cost manufacturing, and safe administration for widespread therapeutic use in cancer therapy as taught by Bialkowski and Pardi.
Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time of filing.
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 16, 23, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-34 of co-pending Application No. 18/008877, herein referred to as “reference application” (now allowed) in view of US 2019/0175727 A1 (Huang, et al., effectively filed 19FEB2019), herein referred to as “’727” and Pardi, et al., Nat Rev, 2018, 17, 261-279), herein referred to as “Pardi.”
The co-pending claims of the reference application recite:
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However, they do not claim: that all mRNAs of the formulation comprise the 5’ Cap 1 structure, and that the antigen-encoding mRNA is HPV.
Nevertheless, ‘727 teaches immunomodulatory therapeutic compositions of mRNA encoding an activating oncogene mutation peptide (i.e., HPV E6/E7) and an mRNA encoding a polypeptide that enhances immune responses (i.e., immunostimulatory proteins) to the activating oncogene mutation peptide (see entire document, specifically see abstract and ¶0264). Specifically, 727 teaches that all mRNAs comprise a 5’ Cap-1 structure and at least one modified nucleoside selected from N1-methylpseudouridine or are fully modified with N1-methypseudouridine (¶0105). Furthermore, the mRNA may be delivered to the subject in the form of a carrier such as a lipid nanoparticle (¶0270). ‘727 highlights that there exists a need in the art for additional effective agents that enhance immune responses to an antigen of interest (¶0005).
The teachings of ‘727 are further supported by the teachings of Pardi, which discloses mRNA vaccine platforms which have high potency, capacity for rapid development, and potential for low-cost manufacturing, and safe administration for widespread therapeutic use (see entire document, specifically see abstract). Furthermore, Pardi teaches that in vitro transcribed mRNA products should optimally contain an open reading frame that encodes the protein of interest, flanking UTRs, a 5’ cap and a poly(A) tail so that the mRNA is engineered to resemble fully processed mature mRNA molecules (see p 262, col 1, ¶2). With regard to the 5’ cap structure, Pardi teaches that synthetic 5’ cap analogues stabilize mRNA and increase protein translation (see box 1). Furthermore, Pardi teaches that TriMix augmented the immunogenicity of naked, unmodified, unpurified mRNA in multiple cancer vaccine studies (p 264, bottom of col 1 and top of col 2). Additionally, Pardi teaches that the mRNA field has benefited from the substantial investment in in vivo small interfering RNA administration, where lipid nanoparticles have been used for over a decade, with lipid nanoparticles becoming one of the most appealing and commonly used mRNA delivery tools (p 266, col 2, lines 14-19 of the cationic lipid and polymer-based delivery section).
It would have been obvious to artisans to modify the lipid nanoparticle comprising one or more mRNA molecules of co-pending claims 32 or 33 of the reference application to include the mRNA molecule encoding the antigen of HPV and that all mRNAs comprised a 5’ Cap 1 structure as taught by ‘727 and Pardi. This is because ‘727 and Pardi teaches that there exists a need in the art for additional effective agents that enhance immune responses to an antigen of interest and because mRNA vaccine platforms require optimal mRNA construction (i.e., 5’ capping technology). One would have been motivated to do so, given the direction by the reference application that the lipid nanoparticle generically comprised one or more mRNAs (i.e., delivery platform for mRNA). There would have been a reasonable expectation of success, given the knowledge that by modifying the lipid nanoparticle taught by the reference nanoparticle by including mRNAs encoding HPV antigens and CD40L, CD70, and caTLR4 which comprise 5’ cap 1 structure as taught by ‘727 and Pardi would lead to mRNA vaccine platforms which have high potency, capacity for rapid development, potential for low-cost manufacturing, and safe administration for widespread therapeutic.
This is a provisional nonstatutory double patenting rejection until publication of the reference application.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. HOPKINS whose telephone number is (703)756-4666. The examiner can normally be reached Mon-Thurs 6:00 AM to 4:00 PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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