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 .
Remark
Applicants’ response and amendment were filed on Nov. 06, 2025. Claims 4 and 21 were amended.
Claims 4-5, 8-21, 24-26, 28-30, 32-33 with elected species of 1-methylpseudouridine and the 1st antigen is HA, subunit H1 and the second antigen is HA different from H1 strain are considered.
Claims 1-3, 22-23, 27, 31 and 34-36 were withdrawn from consideration.
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.
(Withdrawn) The rejection of Claims 4-5, 8-12,16-19, 21, 24-26, 28-30 and 32-33 under 35 U.S.C. 103 as obvious over (Molecular Therapy, 2020, April 19, Vol. 28 (7), pages 1569-1584) to Freyn et al. has been removed necessitated by Applicants’ amendment for changing the HA antigen is a full length.
(New Group of rejection): Claims 4-5, 8-12,16-19, 21, 24-26, 28-30 and 32-33 under 35 U.S.C. 103 as obvious over US 2023/0181715A1 to Nachbagauer et al.
The rejected claims are drawn to an immunogenic composition comprising three nucleotide RNA molecules, The first RNA polynucleotide encodes a full length of hemagglutinin (HA) polypeptide, second RNA polynucleotide encodes a second influenza viral antigen or an immunogenic fragment thereof, and a third one comprising an open reading fragment encodings a third influenza viral antigen or its fragment thereof, wherein the an influenza viral antigens or its fragment thereof that are each from other, wherein each of them is formulated in a lipid nanoparticle (LNP) respectively, wherein the LN is cationic lipid. The antigen is HA as well as other but different each from other and the RNA polynucleotide comprises a modified nucleotide, with 1-methylpseudouridine
Nachbagauer et al. teach an invention related to a composition and a method for making or using the compositions to induce an immune response against at least one influenza infection. The composition comprises mRNA-lipid nanoparticle (mRNA-LNP) vaccines comprising a nucleotide sequence encoding full-length HA immunogens or a modified mRNA-LNP platform with optimized stalk-inducing headless HA immunogens alone or in combination with one or more antigens, adjuvants or a combination thereof, wherein the combination of other influenza viral antigens are NA, NP, and M2e. (See Summary of Invention ). The lipid nanoparticles are included in a formulation comprising a nucleoside-modified RNA as described herein. In some embodiments, such lipid nanoparticles comprise a cationic lipid (See paragraph [0239]). In various embodiments, the lipid nanoparticles have a mean diameter of from about 30 nm to about 150 nm, from about 40 nm to about 150 nm etc. (See paragraph [0240]).
They also teach that at [0219] that one embodiment, the nucleoside is also modified with following group selected rom group consisting of m1acp3Ψ (1-methyl-3-(3-amino-3-carboxypropyl) pseudouridine. In another embodiment, the modified nucleoside is m1Ψ (1-methylpseudouridine). In another embodiment, the modified nucleoside is Ψm (2′-O-methylpseudouridine). In another embodiment, the modified nucleoside is m5D (5-methyldihydrouridine). In another embodiment, the modified nucleoside is m3Ψ (3-methylpseudouridine).
They also teach at [0201] that one embodiment, the mRNA has both a cap on the 5′ end and a 3′ UTR and also3’ poly(A) tail .
The cited reference also teach several lipids of formulars same as claimed in claims 19-and 20 (See Tables I & II) as well as in some embodiments, the LNPs comprise a lipid of Formula (I), a nucleoside- modified RNA and one or more excipients selected from neutral lipids, steroids and pegylated lipids (See Formular I and Table I).
The cited reference also teaches that the influenza virus is an influenza HA group 1 virus, influenza NA group 1 virus, or any combination thereof. In some embodiments, the influenza HA group 1 virus is H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, or any combination thereof. In some embodiments, the influenza NA group 1 virus is N1, N4, N5, N8, or any combination thereof. Thus, in some embodiments, the influenza virus is H1N1, H2N2, H3N2, H5N1, H7N7, H1N2, H9N2, H7N2, H7N3, H10N7, H7N9, H6N1, or any combination thereof. (See paragraph of Description).
While the cited reference do not explicitly teach that the composition comprising 1st and 2nd and 3rd RNA molecules encoding an antigens from different strains, they teaches that the studies used monovalent full-length PR8 or A/Cal09 HA-encoding mRNA-LNP vaccines. Importantly, even these vaccines induced protection from homologous, heterologous and heterosubtypic viruses in mice after one or two immunizations. Therefore, although not bound by any particular theory, it was hypothesized that the use of optimized HA immunogens and the combination of four fairly conserved antigens (headless HA-ferritin, NA, NP and M2e) in multivalent vaccines result in significantly increased protective efficacy. During the course of this study, nucleoside-modified mRNA-LNP formulations encoding influenza A group 1, influenza A group 2 and influenza B antigens (HA, NA, NP and M2e) are evaluated individually and in combined formulations.
It would have been obvious for a person ordinarily skilled in the art to be motivated by the cited reference for making a multivalent influenza vaccine using the RNA molecules encoding HA, NA, NP and M2e from different strains to obtain expected results with a reasonable expectation of success.
Conclusion
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.
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671