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 .
All of the amended claims submitted on 10/18/2024, claims 1-8, 11-12, 15, 24-30 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 3/13/2024 and 10/18/2024 are in compliance with 37 CFR 1.97. Accordingly the references listed in the IDSs are being considered by the examiner.
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 1-8, 11-12, 15, 24-30 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.
Claims 1 and 25 recite the limitation “wherein the SARS-CoV-2 spike protein antigen comprises an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein antigen” (lines 2-5 and 3-7, respectively). From the language of the claims, it is unclear whether this substitution is adding or removing an N-glycosylation site. Claims 2-8, 11-12, 15, 24, and 26-30 depend on claims 1 or 25 but do not resolve this lack of clarity, and are thus also rejected herein.
Additionally, it is noted that an “N-glycosylation site” may involve not only the N residue which is glycosylated, but also two additional residues, i.e., N-X-T or N-X-S. See [0034] of instant specification. In this case, it is not clear if the substitution as claimed may also comprise any mutation that introduces a new N-X-T or N-X-S site as a whole, in addition to the introduction of a new residue N which is glycosylated.
Claim 7 recites the limitation “wherein the amino acid substitution is a D428N substitution”, which refers to a particular residue of a sequence. However, the claim does not provide a reference sequence, so it is unclear which residue is encompassed by the claim.
Claim 15 recites “wherein the SARS-CoV-2 spike protein antigen comprises a C-terminal 13 amino acid deletion.” This limitation is not clear since it is not clear what the “C-terminal 13 amino acid” refers to. E.g., it is not clear if the “C-terminal 13 amino acid” refers to the C-terminal 13 amino acids of the full length wild type SARS-CoV-2 S protein or not.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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 1-5, 7, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guo, et al. (mBio. 2021 May 11;12(3):e00930-21. PMID: 33975938) as evidenced by Yi, et al. (Cell Mol Immunol. 2020 Jun;17(6):621-630. doi: 10.1038/s41423-020-0458-z. Epub 2020 May 15. PMID: 32415260).
These claims are directed a messenger ribonucleic acid (mRNA) comprising an open reading frame (ORF) encoding a SARS-CoV-2 spike protein antigen, wherein the SARS-CoV-2 spike protein antigen comprises an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein antigen not present in the RBD of the wild type SARS-CoV-2 spike protein (claim 1).
Guo teaches that a SARS-CoV-2 spike protein receptor binding domain (RBD) engineered with four novel glycosylation sites is expressed markedly more efficiently and generates a more potent neutralizing response as a DNA vaccine antigen (Abstract). Guo specifically discloses immunization with SARS-CoV-2 spike RBD elicits potently neutralizing antibodies (Fig. 1). Guo also teaches that the engineered glycan at residue 428 (->asparagine) markedly increased RBD expression when fused to a multivalent carrier (Fig. 3; Fig. S3; p. 5, para. 3). Yi, et al. discloses that the SARS-CoV-2 receptor binding motif is from residues 438-508 of the spike protein (Fig. 3). Accordingly, Guo’s engineered glycan (D428N) substitution is N-terminal to a receptor binding motif in the RBD. Guo also discloses that all of the vaccines likely to be available in the first half of 2021 express or deliver a full-length or ectodomain S protein, typically engineered with a pair of prolines designed to enhance the stability of these constructs, and Guo also discloses a proline-stabilized S-protein ectodomain fused at its C terminus to SpyTag and conjugated to a carrier system (p. 5, para. 2). Guo also specifically discloses that the glycan-modified RBD was expressed in Expi293 cells (Fig. 4A).
Figure 3 of Guo shows mutations in the RBD domain of a SARS-CoV-2 polypeptide resulting in the introduction of multiple new N-glycosylation sites (see sites marked in green). Figure 3C shows the sequence of an engineered SARS-CoV-2 RBD polypeptide bearing four novel N-glycosylation motifs. See below:
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Accordingly, Guo teaches an engineered SARS-CoV-2 spike protein antigen comprising an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the RBD of the SARS-CoV-2 spike protein antigen not present in the RBD of the wild type SARS-CoV-2 spike protein.
However, Guo is silent on an mRNA comprising an ORF encoding the engineered SARS-CoV-2 S protein. On the other hand, Guo teaches expression and purification of the engineered protein in host cells. One of skill in the art would readily envisage that such expression processes involve production of mRNA molecules comprising an ORF encoding the engineered protein. In other words, such an mRNA is inherently present in host cells expressing the engineered SARS-CoV-2 S protein antigen.
Regarding claim 15, the engineered SARS-CoV-2 S protein antigens (gRBD peptides) do not comprise the C-terminal 13 amino acids of the wild type S protein. Therefore, claims 1-5, 7, and 15 are anticipated by Guo.
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 (i.e., changing from AIA to pre-AIA ) 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-8, 11-12, 15 and 24-30 are rejected under 35 U.S.C. 103 as being unpatentable over Guo, et al. (mBio. 2021 May 11;12(3):e00930-21. PMID: 33975938), as evidenced by Yi, et al. (Cell Mol Immunol. 2020 Jun;17(6):621-630. doi: 10.1038/s41423-020-0458-z. Epub 2020 May 15. PMID: 32415260; supra), in view of Hoge, et al. (WO2019036670A2, published 2/21/2019; supra) Olmedillas (bioRxiv 2021.05.06.441046; doi: https://doi.org/10.1101/2021.05.06.441046), and/or Higuchi, et al (BioRxiv. 2020.12.14. doi: https://doi.org/10.1101/2020.09.16.299891).
Relevance of Guo is set forth in the 102 rejection above.
Regarding claim 6, Guo is silent on if the SARS-CoV-2 spike protein used in the study has at least 80% identity to SEQ ID NO: 2, 5 or 6.
Regarding claim 8, Guo is silent on if an engineered SARS-CoV-2 spike protein antigen comprising the novel N-glycosylation sites can be made in a SARS-CoV-2 S protein comprising a double proline stabilizing mutation, even though Guo teaches that the full-length proline-stabilized S-protein antigen is used in several prominent COVID-19 vaccines (see page 3, para 2).
Regarding claims 11-12, Guo is silent on if the engineered SARS-CoV-2 spike protein antigen comprising the novel N-glycosylation sites can be made in a SARS-CoV-2 S protein comprising S1 and S2 subunits linked together via a GSGG linker and the claimed positioning site.
Regarding claims 25-30, Guo if silent on making an mRNA vaccine for the engineered SARS-CoV-2 S antigen (sRBD) and the recites lipids, even though it teaches that to evaluate the utility of gRBD in the context of DNA-, mRNA-, or viral vector-based vaccines, the authors developed plasmids expressing wtRBD and gRBD-fusion proteins with five multivalent carriers (See page 7, para 2).
Hoge teaches that nucleic acid vaccines based on messenger RNA (mRNA) have been evaluated for several clinical applications, and have proven to be effective as vaccines against infectious diseases, and there has been considerable focus on modified mRNA vaccines as they are safe, scalable, and offer precision in antigen design (p. 1, para. 2). Hoge further discloses that mRNA vaccines circumvent the problem of pre-existing immunity associated with viral vectors and appear to be more potent than DNA vaccines, and may be especially valuable for emerging infections (p. 1, para. 2). Hoge’s mRNA vaccines include an open reading frame encoding an antigen and a carrier, which is an organic or inorganic ingredient, natural or synthetic, with which the mRNA is combined to facilitate administration (p. 22, para. 5). Hoge also discloses that the antigen may be a viral antigen, from a number of viruses, including Middle East Respiratory Syndrome Corona virus or severe acute respiratory syndrome virus (pp. 23-24, bridging para.).
Hoge also discloses chemical modification of mRNAs can facilitate certain desirable properties of vaccines on the invention, for example, influencing the type of immune response to the vaccine, reducing unwanted innate immune responses, and/or facilitating desirable levels of protein expression of the antigens of interest (pp. 26-27, bridging para.). Hoge explains that “chemical modification” refers to modification with respect to adenosine, guanosine, uridine, or cytidine ribo- or deoxyribonucleosides in one or more of their position, pattern, percent, or population (p. 29, para. 2), and in some embodiments, the at least one chemically modified nucleoside is 1-methyl-pseudouridine (p. 39, para. 1).
Hoge also discloses that its mRNA vaccines are formulated in a lipid nanoparticle (LNP), which enables the effective delivery of modified or unmodified mRNA vaccines, resulting in LNP formulated mRNA vaccines being superior to conventional vaccines by a factor of at least 10 fold or 1,000 fold (pp. 44-45, bridging para.). In some embodiments, the LNP comprises an ionizable lipid, a PEG-modified lipid, a phospholipid, and a structural lipid, with a molar ratio of 50:38.5:10:1.5 of ionizable lipid:cholesterol:DSPC:PEG2000-DMG (p. 45, para. 3). Hoge also discloses that compound of formula I may be of the formula (IIe), wherein R4 is an unsubstituted C1-3 alkyl or –(CH2)N)Q, in which n is 2, 3, or 4, and Q is OH (pp. 54-55), Formula (IIe) with an R4 of –(CH2)2)OH is identical to the instantly claimed compound 1 of claim 28. Hoge also discloses vaccine-induced immunity induced by mRNA encoding full-length H10 formulated in LNP, wherein two groups received a prime and boost immunization by either intramuscular or intradermal administration, and the hemagglutination inhibition titers in all groups were significantly increased after the second immunization and remained above protective levels for the remainder for the study period (p. 76, para. 2; p. 99, paras. 3-5).
Olmedillas discloses structure-based design of a highly stable, covalently-linked SARS-CoV-2 spike trimer with improved structural properties and immunogenicity (title). Olmedillas also specifically discloses SARS-CoV-2 spike ectodomains with a flexible cleavage site linker, between S1 and S2 subunits (summary; Fig. 1A). Olmedillas further discloses S-2P constructs that comprise substitutions of cleavage site residues RRAR with GSAS at positions 682-685 (p. 30, printout, para. 1). Additionally, Olmedillas tested truncated cleavage site linkers of varying length and flexibility to prevent S1/S2 cleavage and improve protein expression (Id.). However, Olmedillas does not specifically disclose the S1 and S2 subunits being linked together via a GSGG linker, or a GSGG linker at position 682 of SEQ ID NO: 6.
Higuchi discloses a codon-optimized RBD of SARS-CoV-2 spike fused to GFP with a GSGG linker (p. 14, para. 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings Guo with Hogo, Olmedillas and/or Higuchi to arrive at the invention as claimed.
Regarding claim 6, requiring that the SARS-CoV-2 spike protein antigen has at least 80% identity to SEQ ID NO: 2, 5, or 6, Guo’s sequence is 97.5% identical to a portion of SEQ ID NO: 5 and SEQ ID NO: 6, and 98.0% identical to a portion of SEQ ID NO: 2 corresponding to the RBD. One of skill in the art would have found it obvious to use a SARS-CoV-2 S protein having an amino acid sequence with as much identity to a circulating wild-type SARS-CoV-2 as the prototype to make the engineered gRBD peptide antigens for vaccine purpose. Such a SARS-CoV-2 S protein is expected to have at least 80% identity to SEQ ID NO: 2, 5 or 6.
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Regarding claim 8’s limitation wherein the SARS-CoV-2 spike protein antigen comprises a double proline stabilizing mutation, Guo discloses that all of the vaccines likely to be available in the first half of 2021 express or deliver a full-length or ectodomain S protein, typically engineered with a pair of prolines designed to enhance the stability of these constructs, and Guo also discloses a proline-stabilized S-protein ectodomain fused at its C terminus to SpyTag and conjugated to a carrier system (p. 5, para. 2). One of skill in the art would have found it obvious to introduce the N-glycosylation mutations of Guo into the S protein antigens with the double-proline mutations so that advantages of both features may be combined.
Regarding claims 11-12, Olmedillas discloses recombinant SARS-CoV-2 spike protein constructs with linkers at position 682-685, which prevent S1/S2 cleavage and improve protein expression. It would have been obvious to one of ordinary skill in the art to test the GSGG linker disclosed by Higuchi. One of ordinary skill in the art would have been motivated to add a linker to prevent S1/S2 cleavage and improve protein expression.
Regarding claim 24, wherein the ORF comprises nucleosides consisting of 1-methylpseudouridine, adenosine, guanosine, and cytidine, that would have been obvious to one of ordinary skill in the art because Hoge discloses chemical modification of mRNAs can facilitate certain desirable properties of vaccines on the invention, for example, influencing the type of immune response to the vaccine, reducing unwanted innate immune responses, and/or facilitating desirable levels of protein expression of the antigens of interest (pp. 26-27, bridging para.). Hoge explains that “chemical modification” refers to modification with respect to adenosine, guanosine, uridine, or cytidine ribo or deoxyribonucleosides in one or more of their position, pattern, percent, or population (p. 29, para. 2), and in some embodiments, the at least one chemically modified nucleoside is 1-methyl-pseudouridine (p. 39, para. 1).
Based on the teachings of Gou and Hoge, a vaccine comprising a messenger ribonucleic acid comprising an open reading frame that encodes a SARS-CoV-2 spike protein antigen, wherein the SARS-CoV-2 spike protein antigen comprises an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the RBD of the SARS-CoV-2 spike protein antigen that is not present in the wild type SARS-CoV-2 spike protein; formulated in a lipid nanoparticle would have been obvious to one of ordinary skill in the art.
Regarding claims 26 and 27, wherein the lipid nanoparticle comprises a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable amino lipid, or any combination thereof, or more specifically the lipid nanoparticle comprises 0.5-15 mol% PEG-modified lipid; 5-25 mol% non-cationic lipid; 25-55 mol% sterol; and 20-60 mol% ionizable amino lipid, that also would have been obvious to a person having ordinary skill in the art, because Hoge discloses LNPs that comprise an ionizable lipid, a PEG-modified lipid, a phospholipid, and a structural lipid, with a molar ratio of 50:38.5:10:1.5 of ionizable lipid:cholesterol:DSPC:PEG2000-DMG (p. 45, para. 3).
Regarding claim 28, wherein the PEG-modified lipid is 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (PEG2000 DMG), the non-cationic lipid is 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC), the sterol is cholesterol, and the ionizable amino lipid has the structure of Compound 1:
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Hoge also discloses that compound of formula I may be of the formula (IIe), wherein R4 is an unsubstituted C1-3 alkyl or –(CH2)N)Q, in which n is 2, 3, or 4, and Q is OH (pp. 54-55), Formula (IIe) with an R4 of –(CH2)2)OH is identical to the instantly claimed compound 1 of claim 28. Therefore, claim 28 would also have been obvious to a person having ordinary skill in the art.
One of ordinary skill in the art would have been motivated to deliver effective vaccines against SARS-CoV-2. There would be a reasonable expectation of success because Hoge demonstrates the effectiveness of LNP mRNA vaccines for viral pathogens and Guo discloses that glycosylation mutants (including D428N) of spike protein exhibit enhanced immunogenic effect.
Regarding claims 29-30, it would have been obvious to use such a vaccine in an amount effective to induce a neutralizing antibody response against SARS-CoV-2 in a subject, and to administer a second dose of the vaccine to the subject. Gou discloses that vaccination with SARS-CoV-2 spike antigens induces neutralizing antibodies, and Hoge discloses that a second mRNA vaccination against another viral protein resulted in hemagglutination inhibition titers in all groups were significantly increased after the second immunization and remained above protective levels for the remainder for the study period.
Therefore, claims 1-8, 11-12, 15 and 24-30 were prima facie obvious before the priority date of the instant invention.
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 25-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 10,702,600 B2 in view of Guo, et al. (mBio. 2021 May 11;12(3):e00930-21. PMID: 33975938), Yi, et al. (Cell Mol Immunol. 2020 Jun;17(6):621-630. doi: 10.1038/s41423-020-0458-z. Epub 2020 May 15. PMID: 32415260), Hoge, et al. (WO2019036670A2, published 2/21/2019), Olmedillas (bioRxiv 2021.05.06.441046; doi: https://doi.org/10.1101/2021.05.06.441046) and/or Higuchi, et al (BioRxiv. 2020.12.14. doi: https://doi.org/10.1101/2020.09.16.299891), as applied in the art rejections above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a vaccine comprising an mRNA encoding a coronavirus S protein antigen formulated in lipid nanoparticle. The instant and ‘600 claims are each drawn to compositions related to mRNA vaccines encoding coronavirus S protein or S protein subunits formulated in a lipid nanoparticle. Where the instant claims are limited to SARS-CoV-2 and require a glycosylation mutation in the RBD and other aspects discussed in great detail above in the rejection under 35 U.S.C. §103, the ‘600 claims are more generically drawn to the ORF encoding a generic betacoronavirus S protein or S protein subunit formulated in a lipid nanoparticle. Notably, the ‘600 claims do not recite a SARS-CoV-2 (or coronavirus) spike protein antigen that comprises an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein antigen not present in the RBD of the wild type SARS-CoV-2 spike protein.
The teachings of Guo, Hoge, Yi, Olmedillas, and Higuchi are described in detail above in the rejection under 35 U.S.C. §103, and it explanation is provided as to how the references’ teachings render obvious the instant invention. Similarly, the ‘600 claims, in view of the teachings of Guo, Hoge, Yi, Olmedillas, and Higuchi, render obvious the instant claims. One of ordinary skill in the art would have been motivated to provide effective and stabilized vaccines against SARS-CoV-2. There would have been a reasonable expectation of success because Guo demonstrates the effect of the N-glycosylation mutation on the SARS-CoV-2 RBD immunogen and Hoge and ‘600 demonstrate the applicability of mRNA vaccines in lipid nanoparticles.
Claims 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 61, and 63-73 of copending Application No. 18/272,512 in view of Guo, et al. (mBio. 2021 May 11;12(3):e00930-21. PMID: 33975938), Yi, et al. (Cell Mol Immunol. 2020 Jun;17(6):621-630. doi: 10.1038/s41423-020-0458-z. Epub 2020 May 15. PMID: 32415260),, Hoge, et al. (WO2019036670A2, published 2/21/2019) Olmedillas (bioRxiv 2021.05.06.441046; doi: https://doi.org/10.1101/2021.05.06.441046) and/or Higuchi, et al (BioRxiv. 2020.12.14. doi: https://doi.org/10.1101/2020.09.16.299891), as applied in the art rejections above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a vaccine comprising an mRNA encoding a coronavirus S protein antigen formulated in lipid nanoparticle. The instant and copending claims are each drawn to compositions related to mRNA vaccines encoding coronavirus S protein or S protein subunits formulated in a lipid nanoparticle. Where the instant claims are limited to SARS-CoV-2 and require a glycosylation mutation in the RBD and other aspects discussed in great detail above in the rejection under 35 U.S.C. §103, the ‘copending claims are drawn to an ORF encoding a fusion protein comprising a RBD and an N-terminal (NTD) of a spike protein, with particular mutations. Notably, the ‘copending claims do not recite a SARS-CoV-2 (or coronavirus) spike protein antigen that comprises an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein antigen not present in the RBD of the wild type SARS-CoV-2 spike protein.
The teachings of Guo, Hoge, Yi, Olmedillas, and Higuchi are described in detail above in the rejection under 35 U.S.C. §103, and it explanation is provided as to how the references’ teachings render obvious the instant invention. Similarly, the copending claims, in view of the teachings of Guo, Hoge, Yi, Olmedillas, and Higuchi, render obvious the instant claims. One of ordinary skill in the art would have been motivated to provide effective and stabilized vaccines against SARS-CoV-2. There would have been a reasonable expectation of success because Guo demonstrates the effect of the N-glycosylation mutation on the SARS-CoV-2 RBD immunogen and Hoge and the copending claims demonstrate the applicability of mRNA vaccines in lipid nanoparticles.
This is a provisional nonstatutory double patenting rejection.
Claims 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 166-185 of copending Application No. 17/797,784in view of Guo, et al. (mBio. 2021 May 11;12(3):e00930-21. PMID: 33975938), Yi, et al. (Cell Mol Immunol. 2020 Jun;17(6):621-630. doi: 10.1038/s41423-020-0458-z. Epub 2020 May 15. PMID: 32415260),, Hoge, et al. (WO2019036670A2, published 2/21/2019) , Olmedillas (bioRxiv 2021.05.06.441046; doi: https://doi.org/10.1101/2021.05.06.441046) and/or Higuchi, et al (BioRxiv. 2020.12.14. doi: https://doi.org/10.1101/2020.09.16.299891), as applied in the art rejections above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a vaccine comprising an mRNA encoding a coronavirus S protein antigen formulated in lipid nanoparticle. The instant and copending claims are each drawn to compositions related to mRNA vaccines encoding coronavirus S protein or S protein subunits formulated in a lipid nanoparticle. Where the instant claims are limited to SARS-CoV-2 and require a glycosylation mutation in the RBD and other aspects discussed in great detail above in the rejection under 35 U.S.C. §103, the ‘copending claims are drawn to an ORF encoding a fusion protein comprising a RBD, an N-terminal (NTD) of a spike protein, and a transmembrane domain with particular linkers. The full-length spike protein sequence, bearing sequences between each of these domains is interpreted to possess such linking sequences. Notably, the ‘copending claims do not recite a SARS-CoV-2 (or coronavirus) spike protein antigen that comprises an amino acid substitution relative to a wild type SARS-CoV-2 spike protein, wherein the amino acid substitution comprises an N-glycosylation site in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein antigen not present in the RBD of the wild type SARS-CoV-2 spike protein.
The teachings of Guo, Hoge, Yi, Olmedillas, and Higuchi are described in detail above in the rejection under 35 U.S.C. §103, and it explanation is provided as to how the references’ teachings render obvious the instant invention. Similarly, the copending claims, in view of the teachings of Guo, Hoge, Yi, Olmedillas, and Higuchi, render obvious the instant claims. One of ordinary skill in the art would have been motivated to provide effective and stabilized vaccines against SARS-CoV-2. There would have been a reasonable expectation of success because Guo demonstrates the effect of the N-glycosylation mutation on the SARS-CoV-2 RBD immunogen and Hoge and the copending claims demonstrate the applicability of mRNA vaccines in lipid nanoparticles.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671
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