DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group I, and election of selected species without traverse, in the reply filed on July 7, 2026 is acknowledged. The traversal is on the ground(s) that there would not be a serious search burden to examine the claims of Groups I and II. This is not found persuasive because search burden is not a criterion for determining lack of unity in national stage applications. The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 3, 4, 6, 9, 10, 13-15 and 26 are under examination with regard to the elected species. It is noted that Applicant elected SEQ ID NO: 15 from claims 12 and 29, however, SEQ ID NO: 15 represents a construct having not only the elected mutation D614G, but also RRRR to QQAA mutations. Since the RRRR to QQAA mutation was not elected, SEQ ID NO: 15 does not represent the elected species in claim 6 (D614G only).
Claims Summary
Claim 1 is directed to a self-replicating RNA (also called self-amplifying RNA, or replicon) comprises a nucleotide sequence encoding a SARS-CoV-2 antigen operably linked to a subgenomic (SG) promoter. The specification defines “self-replicating RNA” as a construct based on an RNA virus that has been engineered to allow expression of heterologous RNA and proteins (see paragraph [0172] of the published application US 2024/0024460). The antigen is a spike (S) protein (claim 3), specifically, a mutant S protein (claim 4, elected species) comprising a D614G mutation corresponding to SEQ ID NO: 18 (claim 6, elected species). The SG promoter comprises SEQ ID NO: 9 (claim 9). SEQ ID NO: 9 represents a 49-nt alphavirus native SG promoter. The self-replicating RNA is from an alphavirus selected from SFV, SIN, VEE and combinations thereof (claim 10). Also claimed is an immunogenic composition comprising the self-replicating RNA (claim 13), or a plurality of self-replication RNAs, each encoding a different polypeptide antigen sequence (claim 14). Also claimed a pharmaceutical composition comprising an immunogenic composition comprising the self-replicating RNA, a pharmaceutically acceptable carrier, wherein the RNA is encapsulated in, bound to or adsorbed on an LNP, a polymeric microparticle or an O/W emulsion (claim 15). Also claimed is a recombinant DNA plasmid encoding the self-replicating RNA (claim 26).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 4, 10, 15 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McKay et al. (Nature Communications, published July 2020, 11, Article No. 3523, 7 pages, “McKay”, cited in the IDS filed June 2, 2023). The claims are outlined above and correlated with the teachings of the prior art in bold font below.
McKay discloses a DNA plasmid vector that synthesizes a self-amplifying RNA (saRNA) vector based on VEEV that comprises a subgenomic promoter operably linked to a coding sequence for SARS-COV-2 pre-fusion stabilized S protein (stabilized by proline substitutions) (see abstract and page 4, “Vectors” section) (claims 1, 3, 4, 10 and 26). For formulation of an immunogenic composition, an aqueous solution of the saRNA is mixed with an ethanolic lipid mixture resulting in encapsulation in LNP (see abstract, page 2, left column, third paragraph, and page 6, “Formulation of saRNA” section) (claim 15). Therefore, the claimed embodiments are anticipated by the prior art.
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 1, 3, 10, 13-15 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Geall et al. (US 2011/0300205 A1, “Gaell”) in view of Wu et al. (Nature, published February 2020, 579:265-269, “Wu”) and Perri et al. (US 2009/0104226 A1, “Perri”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Gaell discloses self-replicating RNA molecules comprising a SG promoter operably linked to a heterologous sequence encoding an antigen, for the purpose of vaccination (see paragraphs [0008] and [0057]) (claim 1). The self-replicating RNA is from an alphavirus, such as SIN, SFV and VEE (see paragraph [0058]) (claim 10). The antigen is from any of a variety of pathogens, including coronaviruses, such as SARS (see paragraph [0130]). Gaell discloses plasmid DNA encoding the replicon (see paragraph [0170]) (claim 26). Also disclosed are pharmaceutical and immunogenic compositions comprising the self-replicating RNA in combination with a pharmaceutically acceptable carrier, and encapsulated in, bound to or adsorbed on a lipid, such as an LNP, or O/W emulsion, among other choices (see paragraphs [0024]-[0025] and [0221]) (claims 13 and 15).
Gaell does not disclose SARS-CoV-2 S protein and it was not known at that time. However, it would have been obvious to have employed any antigen in Gaell’s construct. Wu discloses the S protein of the emerging pathogen SARS-CoV-2 (see Figure 1). One would have been motivated to express Wu’s SARS-CoV-2 S protein in Gaell’s construct since it is an emerging pathogen against which a vaccine or immunogenic composition would be desirable (claims 1 and 3). One would have had a reasonable expectation of success of expression of the S protein from the replicon in view of Perri’s alphavirus replicon vectors expressing respiratory pathogen antigens for use as vaccines against, for example, SARS-CoV, comprising the S protein (see abstract and paragraph [0171]).
Gaell discloses RNA molecules expressing multiple antigens (see paragraph [0075]), but does not disclose a single composition comprising multiple self-replicating RNA molecules expressing different antigens. However, it would have been obvious to have constructed multiple RNA molecules expressing different antigens for use in a single composition. One would have been motivated to broaden the breadth of immunogenicity by including additional molecules expressing different antigens, with a reasonable expectation of success (claim 14). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Geall et al. (US 2011/0300205 A1, “Gaell”) in view of Wu et al. (Nature, published February 2020, 579:265-269, “Wu”) and Perri et al. (US 2009/0104226 A1, “Perri”), as applied to claim 1 above, and further in view of Korber et al. (Cell, August 20, 2020, 182(4):812-827, “Korber”).
Claim 4 is directed to an embodiment wherein the S protein is a mutant S protein. Claim 6 is directed to an embodiment wherein the mutant S protein has the substitution D614G.
The teachings of Gaell, Wu and Perri are outlined above, none of which disclose a mutant S protein, or a mutant S protein having a D614G mutation. However, it would have been obvious to have used a mutant S protein, such as one that has the D614G mutation. One would have been motivated to use a mutant S protein having the D614G mutation because of the global prevalence of the SARS-CoV-2 variant viruses that comprises the D614G mutation in the S protein (see Korber, abstract). Given that Gaell’s construct is suitable for any antigen, would have had a reasonable expectation of success.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Geall et al. (US 2011/0300205 A1, “Gaell”) in view of Wu et al. (Nature, published February 2020, 579:265-269, “Wu”) and Perri et al. (US 2009/0104226 A1, “Perri”), as applied to claim 1 above, and further in view of Weiss et al. (US 2020/0040338, published February 6, 2020, filed August 1, 2019, “Weiss”).
Claim 9 is directed to an embodiment wherein the SG promoter comprises SEQ ID NO: 9.
The teachings of Gaell, Wu and Perri are outlined above. While Gaell discloses the use of a SG promoter, there is no disclosure of SEQ ID NO: 9. It would have been obvious to have used any SG promoter in Gaell’s construct. Weiss discloses saRNA from an alphavirus, such as SIN, SMF and VEEV (see abstract and paragraph [0048]), expressing a heterologous molecule (see paragraph [0004]), wherein the saRNA comprises a subgenomic promoter, SGP30 (SEQ ID NO: 16), which contains instant SEQ ID NO: 9 (see Table 3 and paragraph [0007]). The patent’s SEQ ID NO: 16, nt 80-128, matches instant SEQ ID NO: 9, nt 1-49. One would have had a reasonable expectation of success in view the similarity of the constructs of Gaell and Weiss.
Conclusion
No claim is allowed.
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/STACY B CHEN/Primary Examiner, Art Unit 1672
