DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of species L452 in the reply filed on June 15, 2026 is acknowledged. Claims 1, 10, 11 and 61-73 are under examination. Claims 4 and 60 are withdrawn from consideration being directed to non-elected subject matter.
Claims Summary
Claim 1 is directed to an mRNA comprising an ORF encoding a fusion protein. The fusion protein comprises an RBD and an N-terminal domain (NTD) of a SARS-CoV-2 S protein. The fusion protein does not contain a full-length SARS-CoV-2 S protein. (It is noted that the limitation “the fusion protein does not contain a full-length SARS-CoV-2 S protein” is not found verbatim in the specification, but was introduced in a preliminary amendment. However, support for this limitation is found in paragraph [0121] of the published application US2024/0100151-A1.) The fusion protein comprises a substitution mutation at position L452 relative to SEQ ID NO: 36. (The earliest disclosure of the L452 mutation is in provisional application USSN 63/140,921, filed January 24, 2021, see page 16/103, first paragraph.) SEQ ID NO: 36 is 1273-aa and represents a wild-type SARS-CoV-2 S protein. The fusion protein further comprises a transmembrane domain (TD) linked to the NTD and/or the RBD (claim 10). The TD is an influenza HA transmembrane domain (HATM) (claim 11), and the fusion protein comprises NTD-RBD-TD (claim 62). The RBD and the NTD are linked through a non-cleavable linker (claim 63).
The fusion protein comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 57. SEQ ID NO: 57 is 521-aa and represents the ORF of the fusion protein. (SEQ ID NO: 57 does not have the substitution mutation at position L452 relative to SEQ ID NO: 36.)
The mRNA comprises a chemical modification (claim 64), specifically 1-methyl-pseudouridine (m1ψ) (claims 65 and 66). The ORF comprises 1-methyl-pseudouridine (m1ψ), adenosine, guanosine and cytosine (claim 67).
Also claimed is a composition comprising the mRNA formulated in an LNP (claim 68), wherein the LNP comprises a molar ratio of 20-60 mol% ionizable amino lipid, 2-25 mol% neutral lipid, 25-55 mol% sterol, and 0.5-15 mol% PEG-modified lipid. The ionizable amino lipid comprises, for example, SM-102 (claims 70-72). Claim 73 is directed to a method of inducing an antigen-specific immune response in a subject by administering the composition to the subject in an effective amount to produce an antigen-specific immune response.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 10, 11 and 61-73 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 and all dependent claims recite, “wherein the fusion protein comprises an amino acid mutation relative to SEQ ID NO: 36”. Since the claims are not limited to SEQ ID NO: 36, as SEQ ID NO: 36 only serves as a reference point for identifying a substitution at a position that corresponds to amino acid L452 of SEQ ID NO: 36, the claims do not identify the location of the mutation within the context of the fusion protein, i.e., in the RBD portion of the fusion protein. Without this information, one would not know where the mutation is located. The metes and bounds of the claims cannot be determined without further clarification. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. Claim 1 is directed to an mRNA comprising an ORF encoding a fusion protein that comprises an RBD and an NTD of a SARS-CoV-2 S protein, wherein the fusion protein does not contain a full-length SARS-CoV-2 S protein, and wherein the fusion protein comprises a substitution mutation at position L452 relative to SEQ ID NO: 36. Claim 10 is directed to an embodiment wherein the fusion protein further comprises a transmembrane domain (TD) linked to the NTD and/or the RBD. The mRNA of claim 1 and the mRNA of claim 10 are not markedly different from an mRNA comprising an NTD, RBD and TD, all of which are found in the S protein of SARS-CoV-2. Although the claims use the term “fusion protein” and exclude full-length S proteins, there is no definition in the specification nor a recitation of other structural components in the claims that distinguish the claimed “fusion protein” from a naturally occurring S protein fragment having all but the cytoplasmic domain (CT) at the C-terminus. The TD is linked to the RBD and NTD by way of other portions of the S protein. Note that the linker in claim 10 is not defined as any particular structure. Zhang et al. (medRxiv 2021.01.18.21249786, posted January 20, 2021, available from www.medrxiv.org/content/10.1101/2021.01.18.21249786v1.full.pdf, 6 pages) discloses a novel SARS-CoV-2 strain, CAL.20C, which has an L452R substitution. Li et al. (Cell, September 3, 2020, 182:1284-1294, e1-e6 and supplemental figures, 21 pages total) discloses a natural variant SARS-CoV-2 strain having an L452R substitution in the S protein (see abstract, page 1285, first paragraph of “Results” section, and page 1289, right col., second full paragraph). Taken together, an mRNA encoding an S protein fragment (minus the CT domain) from the natural strains of Zhang et al. or Li et al. conveys the same amino acid information as the instantly claimed fusion protein in its broadest reasonable interpretation. This mRNA is a judicial exception.
This judicial exception is not integrated into a practical application because the claims are directed to mRNA alone. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are directed to mRNA alone. Therefore, the claims are directed to a judicial exception and are not patent eligible.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Li et al. (Cell, September 3, 2020, 182:1284-1294, e1-e6 and supplemental figures, 21 pages total) discloses a natural variant SARS-CoV-2 strain having an L452R substitution in the S protein (see abstract, page 1285, first paragraph of “Results” section, and page 1289, right col., second full paragraph). Li used the S protein sequence to make a pseudotyped virus via a plasmid vector pcDNA3.1.S2-L452R (see page e3). US2021/0251898-A1 discloses mRNA encoding fusion proteins comprising SARS-CoV S protein, as well as LNPs. US2019/0351048-A1 (cited in the IDS filed 10/26/2023) discloses mRNA encoding fusion proteins comprising MERS RBD, as well as LNP formulations. While these reference disclose portions of the claimed invention (e.g., claim 1), there is no teaching or fair suggestion to arrive at an mRNA comprising an ORF encoding a fusion protein comprising and RBD with an L452 mutation and an NTD, wherein the fusion protein does not comprise a full-length S protein.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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