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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/30/25 has been entered.
Rejection Maintained
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1, 7, 20, 23, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Bancel et al. (US20140193482A1) and Kwong et al. (USPGPubUS20160046675A1).
Bancel et al. teach for claim 1, a lipid nanoparticle and an RNA encoding an RSV antigen (paras 666, 819, and 831). For claim 1, Bancel et al. teach that the modification, 1-methyl-pseudouridine, has been shown to convey added protection over the standard combination of 5-ethylcytidine/ pseudouridine explored by others resulting in twice as much protein and almost 150 fold reduction in immune activation (see paragraph [1571]).
For claims 1, 20, and 35, the nanoparticle can contain cationic lipid, PEG-modified lipid, a sterol and a non-cationic lipid including DLin-MC3-DMA including neutral lipid and cholesterol (paras 28 and 578).
Bancel et al. do not teach RSV F.
For claims 1 and 7, Kwong et al. teach SEQ ID# 324 that is 99.7% identical (see sheet).
For claim 23, since the prior art has the same structure, the claims would have the same property of net neutral charge. For claim 35, the RNA can be administered to treat a virus (para 837).
Bancel et al. do not teach RSV F.
For claim 1, Kwong et al. teach that RSV F can be stabilized in prefusion conformation and is useful as an antigen in a vaccine as a nucleic acid. Kwong et al. includes nucleic acids encoding the RSV F constructs used as antigens and in methods to induce immune response (para 13), that the antigens can be used as vaccines (end of para 6) and “In additional embodiments, a therapeutically effective amount of a pharmaceutical composition including a nucleic acid encoding a disclosed PreF antigen is administered to a subject in order to generate an immune response. In one specific, non-limiting example, a therapeutically effective amount of a nucleic acid encoding a disclosed antigen is administered to a subject to treat or prevent or inhibit RSV infection (para 561).”
One of ordinary skill in the art at the effective time of filing would have known RSV F protein and a nucleic acid encoding antigen for RSV as taught by Kwong et al.
One of ordinary skill in the art at the effective time of filing would have known that certain modifications improve the stability and expression of mRNA and would have been motivated to use the modifications to improve the mRNA in vivo along with the lipid nanoparticle adjuvant as a delivery component.
Thus, it would have been prima facie obvious before the effective time of filing to modify the particle of Bancel et al. with the expectation of success knowing that lipid nanoparticles are known to be effective in invoking an immune response and then to modify the composition to use the stabilized prefusion RSV F of Kwong et al. with the expectation of success knowing that it is taught to be immunogenic (abstract) and stabilized (Figure 12).
Applicant argues that Kwong et al. teachings are drawn mainly to protein antigens, that their nucleic acids are plasmids not mRNAs, and there is only a high-level statement that nucleic acids of the invention can be administered.
Applicant also argues that there is a difference between protein and mRNA vaccines citing Brio et al. (previously provided). Applicant shows a figure from the paper that shows mRNA performed poorly and did not perform as well as protein. Arguing there is no expectation of success alone or in combination with Bancel et al. and Kwong et al.
Applicant concludes that their invention with N1-methyl-pseudouridine and four-part lipid results in an efficacious vaccine, and points to Figures 2, 3A-C, 4A-C, 8, 11,12 etc. elicit a strong response. Thus, the references do not provide a motivation or expectation of success.
Applicant’s arguments have been fully considered and not found persuasive.
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). Here, Kwong et al. provide the antigen and suggestion that it can be administered as nucleic acid. Bancel et al. provide the method and details to make the lipid formulations and the modifications to mRNA including using N1-methyl-pseudouridine.
Applicant argues Brito et al. makes RSV F mRNA unpredictable but the paper does not cast doubt on the claimed invention because it is different from the claimed invention as set out as follows:
As to the teachings of Brito et al., it appears that they used a MEGAscript T7 kit and that does not contain N1-methyl-pseudouridine and the paper references RSV F from a prior work and that references post fusion RSV F and does not mention any modifications that would stabilize the RSV F in pre-fusion conformation. Thus, the reference is different from the claimed invention.
Brito et al. Figure 2 as pointed out by applicant, is drawn to comparing adjuvants and their own SAM (self-amplifying mRNA). The result of the RSV F mRNA does not seem to be a concern (discussed on page 2119 column 2).
As to applicant’s efficacious vaccine, uses a specific mRNA and specific four-part lipid formulation. The claims include any mRNA that encodes a pre-fusion RSV F and any lipid formulation that comprises an ionizable cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid.
Allowable Subject Matter
Sequence No: 8 (100% identity) is free of the prior art. The 90% limitation is addressed in the 103 rejection.
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 MYRON G HILL whose telephone number is (571)272-0901. The examiner can normally be reached on Mon-Fri.
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MYRON G. HILL
Examiner
Art Unit 1671
/M.G.H/ Examiner, Art Unit 1671
/Shanon A. Foley/Primary Examiner, Art Unit 1671