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 .
Response to Amendment
The Amendment filed 06/15/2026 in which claims 190 and 202 were amended has been entered. Claims 208 – 210 have been added.
Claims 190 – 202 and 208 - 210 are under examination on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(Previous rejection, withdrawn) Claim 202 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inducing an immune response against in some cases, does not reasonably provide enablement for .
Applicant has amended the claims.
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.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190 - 198, 201 - 202, and 205 - 207 were rejected under 35 U.S.C. 103 as being unpatentable over Oostvogels et al. (US20220211838A1, hereinafter, "Ootsvogels").
Claims 205 – 207 have been cancelled. Claims 190 and 202 have been amended.
Claims 190 - 198 and 201 - 202 are rejected under 35 U.S.C. 103 as being unpatentable over Oostvogels et al. (US20220211838A1, hereinafter, "Ootsvogels") in view of Nolan et al (US20020064798A1, hereinafter, “Nolan”), Troup et al (Open exploration, 2020, 10.37349/etat.2020.00018, hereinafter, “Troup”), Sivaramakrishnan et al (PNAS, 2011, 10.1073/pnas.1116066108, hereinafter, “Sivaramakrishnan”), and Nagamune et al (Nano Converg, 2017, 10.1186/s40580-017-0103-4, hereinafter, “Nagamune”) , as evidenced by Daniels et al (Surveillance report, 2012, hereinafter, “Daniels”).
Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract).
Regarding claim 190, Ootsvogels teaches a combination vaccine that encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein, which consists of the receptor binding domain (RBD), the N-terminal domain (NTD), and 2 subdomains (Abstract, Claim 1, ¶0101, ¶0102), and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with at least one uracil replaces by N1-methylpseudouridine (m1ψ) nucleotide (¶0411), stating a preference for all of the uracil nucleotides replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels teaches that the heterologous peptide encoding at least one antigen from a coronavirus may further encode a linker peptide (¶0121, 0122).
Regarding claim 191, Ootsvogels teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein (Claim 1 – 3).
Regarding claim 192, Ootsvogels teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus neuraminidase (NA) protein (Claim 3 – 6, ¶0754).
Regarding claim 193, Ootsvogels teaches the combination vaccine comprising of mRNA encoding the HA protein from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8). Please note, Daniels evidences that B/Brisbane/60/2008 as a B/Victoria lineage virus (Summary).
Regarding claim 194, 195, and 196, Ootsvogels teaches the first, second, and third mRNA can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19).
Regarding claim 197, Ootsvogels teaches an LNP comprises 20-60% cationic lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-15% PEG-lipid (Claim 1).
Regarding claim 198, Ootsvogels teaches an LNP comprises 40-50% cationic lipid (¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Regarding claim 201, Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21).
Regarding claim 202, Ootsvogels teaches the method for administering the combination vaccine to treat a respiratory virus infection (Abstract, ¶1526).
Ootsvogels does not teach a linker comprising the sequence GGGS.
However, regarding claim 190, Nolan teaches fusion proteins that can be used to screen drug agents for bio activity (Abstract). Nolan teaches linkers allow components of constructs to interact with potential targets unhindered (¶0079). Nolan teaches that glycine-polymers such as GGGS are flexible linkers that are relatively unstructured, serve as neutral tethers, and have been shown to be effective for fusing peptides together (¶0079).
It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal linker for use in the method taught by Ootsvogels to maximize the biological activity of the fusion protein with a reasonable expectation of success.
Identifying the optimal linker for fusion proteins through trial and error is routine experimentation for engineering proteins. Troup teaches the design of PROTAC linkers and highlights “important limitations associated with the traditional “trial and error” approach around linker design and selection”. Sivaramakrishnan teaches identifying ideal linkers to control inter-protein interaction of a fusion protein, stating protein activity “changing the specific linker sequence by trial and error”. The routine optimization of linkers is ubiquitous in laboratories and has led to a push to computationally determine the optimal linker sequence as taught by Nagamune. Nagamune reviews the state of protein engineering, including the engineering of fusion proteins. Nagmune teaches that “[m]]ost current approaches to linker selection and design processes for fusion proteins are still largely dependent on experience and intuition… To overcome this problem, the computational prediction of fusion protein conformation and linker structure can be considered a cost-effective alternative to experimental trial-and-error linker selection”.
Here, the instant claim encompasses selecting a linker sequence for the fusion protein and as such is readily obtained by routine optimization.
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to optimize the linker taught by Nolan in order to advantageously titrate biological activity. One of ordinary skill in the art would have reasonable expectation of success in selecting a linker given that these methods are well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 199 - 200 and 203 - 204 were rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella et al. (PCT/US19/15412, hereinafter, “Ciaramella”) as applied to claims 190 - 198, 201 - 202, and 205 - 207 above, and further in view of Oostvogels, as evidenced by Daniels.
Claims 203 and 204 have been cancelled.
Claims 199 and 200 are rejected under 35 U.S.C. 103 as being unpatentable over Oostvogels, Nolan, Troup, Sivaramakrishnan, and Nagamune as applied to claims 190 - 198 and 201 - 202 above, and further in view of Ciaramella et al. (PCT/US19/15412, hereinafter, “Ciaramella”).
As discussed above, claims 190 – 198 and 201 – 202 were rendered prima facie obvious by the teachings of Oostogogels, Nolan, Troup, Sivaramakrishnan, and Nagamune. The reference fails to teach the exact ionizable amino lipid, a component of LNPs, of claims 199 and 200.
However, Ciaramella teaches an RSV RNA vaccine that comprises of a mRNA polynucleotide encoding the RSV F protein and an LNP. The structure of the ionizable amino lipid in Ciaramella has the exact structure of the ionizable amino lipid claimed in 199 and 200 of the instant application (Compound 1 of Ciaramella, reproduced below).
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Ootsvogels and Ciaramella are considered to be analogous to the claim invention because they both aim to treat and prevent SARS-CoV-2, influenza, and RSV infections through the use of mRNA vaccines that target two or more viruses in one composition. Ootsvogels and Ciaramella teach that the efficacy of the vaccine can change depending on the LNP used in conjunction with the mRNA (Ootsvogels ¶1287, ¶1289; Ciaramella ¶0119). Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized method to use the combination of mRNA polynucleotides of SARS-CoV-2, Influenza, and RSV as taught by Ootsvogels with the specific LNP taught by Ciaramella because doing so would advantageously allow one to increase the effectiveness of the payload delivery and allow for a stronger vaccination against SARS-CoV-2, Influenza, and RSV. One of ordinary skill in the art would have reasonable expectation of success in using a different LNP to protect mRNA from degradation, enhance endosomal escape, and/or promote cell uptake (Guimaraes et al. J Control Release, 2019; Abstract, Introduction ¶2) given that this method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(New rejection, as necessitated by amendments) Claims 208 – 210 are rejected under 35 U.S.C. 103 as being unpatentable over Oostvogels, Nolan, Troup, Sivaramakrishnan, and Nagamune as applied to claims 190 - 198 and 201 - 202 above, and further in view of Joyce et al (US20230285539A1, hereinafter, “Joyce”).
As discussed above, claims 190 – 198 and 201 – 202 were rendered prima facie obvious by the teachings of Oostvogels, Nolan, Troup, Sivaramakrishnan, and Nagamune. The references fail to teach the fusion protein encoded by the second ORF lacking a SD1 and/or SD2 domain.
However, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
Oostvogels, Nolan, Troup, Sivaramakrishnan, Nagamune and Joyce are considered to be analogous to the claim invention because they teach fusion proteins and methods of improving the biological activity of the fusion proteins. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to create a fusion protein composition comprised of NTD, and RBD of a SARS-CoV-2 protein that is specifically lacking the SD1 and/or SD2 domain because it is a known configuration of the antigens that has been used to treat or lessen the risk of SARS-CoV-2 infection. One of ordinary skill in the art would have had a reasonable expectation of success in engineering a fusion protein composition comprised of NTD, and RBD of a SARS-CoV-2 protein that is specifically lacking the SD1 and/or SD2 domain given that it is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
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.
1.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190 - 202 and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 108 - 119 and 126 - 128 of copending Application No. 18555130 in view of Oostvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claim 108 of ‘130 teaches a combination vaccine comprising of a mRNA encoding an influenza virus HA protein, a second mRNA comprising the RBD and NTD of a SARS-CoV-2 spike protein with a linker comprising GGGS, with both mRNA containing N1-methylpseudouridine, adenosine, guanosine, and cytidine, and where first and second mRNA polynucleotides is formulated in at least one LNP.
Claim 109 of ‘130 teaches the use of three different influenza virus HA proteins, with claim 110 teaches the further encoding of three different virus NA proteins.
Claim 111 of ‘130 teaches the three different influenza virus HA proteins are from an H1N1 virus, H3N2 virus, and an influenza B/Victories lineage virus.
Claim 112 of ‘130 teaches the first and second mRNA care formulated in separate LNPs while claim 113 teaches the first and second mRNA care formulated in a single LNP.
Claim 114 of ‘130 teaches the LNP composition comprises 20-60 mol% ionizable amino lipid, 5-25 mol% non-cationic lipid, 25-55 mol% sterol, and 0.5-15 mol% PEG-modified lipid.
Claim 115 of ‘130 teaches the LNP composition comprises 40-50 mol% ionizable amino lipid, 20-40 mol% cholesterol, 5-15 mol% neutral lipid, and 0.5-3 mol% PEG-modified lipid.
Claim 116 of ‘130 teaches the ionizable lipid structure (reproduced below) where R1 is selected from the group consisting of C530 alkyl, C520 alkenyl, and -R"M'R'; R2 and R3 are independently selected from the group consisting of C1-i4 alkyl and C2-i4 alkenyl; R4 is -(CH2)nQ, wherein Q is -OR, and n is selected from 1, 2, 3, 4, and 5; each Rs is H; each R6 is H; M and M' are independently selected from -C(O)O- and -OC(O)-; R7 is H; RisH;R' is selected from the group consisting of C1-18 alkyl and C2-18 alkenyl; R" is selected from the group consisting of C3-14 alkyl and C3-14 alkenyl; and m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
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Claim 117 of ‘130 teaches the exact structure of the ionizable amino lipid (reproduced below).
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Claim 118 of ‘130 teaches the method of administering the combination vaccine of claim 108 to the subject.
Claim 119 of ‘130 teaches the method of preventing a respiratory virus infection in a subject by administering the combination vaccine of claim 108 to the subject.
Claim 126 of ‘130 teaches the combination vaccine of claim 108, wherein the fusion protein encoded by the second ORF does not include an SD1 domain.
Claim 121 of ‘130 teaches the combination vaccine of claim 108, wherein the fusion protein encoded by the second ORF does not include an SD2 domain.
Claim 127 of ‘130 teaches the combination vaccine of claim 108, wherein the fusion protein encoded by the second ORF does not include an SD1 domain and does not include an SD2 domain.
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization.
Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to treat a respiratory virus infection (Abstract, ¶1526).
The scope of the claims of ‘130 and the instant application significantly overlap. These claims in view of Ootsvogels make claims 190 – 202 and 208 – 210 of the instant application obvious. The general idea of using an mRNA vaccine to prevent or treat an influenza, RSV, and/or SARS-CoV-2 using the same LNP composition and method of administration in the same manner is discussed in both sets of claims. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘087 to include the mRNA encoding for all three SARS-CoV-2, RSV, and influenza antigens because doing such can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
2.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 - 201, and 208 – 210 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 - 10, and 12 of U.S. Patent No. US11911453B2 in view of Oostvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claim 1 of the conflicting patent teaches a vaccine comprising of a mRNA encoding an RSV F protein and an LNP comprising 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid.
Claim 4 and 5 of conflicting patent teaches the mRNA of claim 1 of conflicting literature comprised of at least 80% 1-methyl-pseudouridine.
Claim 6 of conflicting patent teaches the LNP comprising 40-50 mol % ionizable cationic lipid, 10-20 mol % neutral lipid, 35-45 mol % cholesterol, and 1-5 mol % PEG-modified lipid.
Claim 7 of conflicting patent teaches the ionizable lipid structure (reproduced below) where:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, —R*YR″, —YR″, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, C2-14 alkenyl, —R*YR″, —YR″, and —R*OR″, or R2 and R3, together with the atom to which they are attached, form a heterocycle or carbocycle;
R4 is selected from the group consisting of a C3-6 carbocycle, —(CH2)nQ, —(CH2)nCHQR, —CHQR, —CO(R)2, and unsubstituted C1-6 alkyl, where Q is selected from a carbocycle, heterocycle, —OR, —O(CH2)nN(R)2, —C(O)OR, —OC(O)R, —CX3, —CX2H, —CXH2, —CN, —N(R)2, —C(O)N(R)2, —N(R)C(O)R, —N(R)S(O)2R, —N(R)C(O)N(R)2, —N(R)C(S)N(R)2, —N(R)R8, —O(CH2)nOR, —N(R)C(═NR9)N(R)2, —N(R)C(═CHR9)N(R)2, —OC(O)N(R)2, —N(R)C(O)OR, —N(OR)C(O)R, —N(OR)S(O)2R, —N(OR)C(O)OR, —N(OR)C(O)N(R)2, —N(OR)C(S)N(R)2, —N(OR)C(═NR9)N(R)2, —N(OR)C(═CHR9)N(R)2, —C(═NR9)N(R)2, —C(═NR9)R, —C(O)N(R)OR, and —C(R)N(R)2C(O)OR, and each n is independently selected from 1, 2, 3, 4, and 5;
each R5 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
each R6 is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —N(R′)C(O)—, —C(O)—, —C(S)—, —C(S)S—, —SC(S)—, —CH(OH)—, —P(O)(OR′)O—, —S(O)2—, —S—S—, an aryl group, and a heteroaryl group;
R7 is selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
R8 is selected from the group consisting of C3-6 carbocycle and heterocycle;
R9 is selected from the group consisting of H, CN, NO2, C1-6 alkyl, —OR, —S(O)2R, —S(O)2N(R)2, C2-6 alkenyl, C3-6 carbocycle and heterocycle;
each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
each Y is independently a C3-6 carbocycle;
each X is independently selected from the group consisting of F, Cl, Br, and I; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
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Claim 10 of conflicting patent teaches the exact structure of the ionizable amino lipid (reproduced below).
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Claims 12 of conflicting patent teaches the method of administering the vaccine of claim 1 induce an immune response to the subject.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting patent and the instant application significantly overlaps. These claims make claims 190, 197 – 201, and 208 - 210 of the instant application obvious. While ‘453 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding an RSV antigen can be included with mRNAs encoding antigens from influenza and coronaviruses which are formulated with an LNP. Furthermore, the use of a mRNA encoding the RSV F protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘453 to include the mRNA encoding for RSV with the influenza and SARS-CoV-2 antigens because doing such can lower costs while still effectively treating and/or reducing the severity of RSV, influenza, and SARS-CoV-2 infection.
3.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 - 201, and 209 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 20, and 35 of copending Application No. 18314980 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, Joyce, and Ciaramella as discussed above.
Claims 1 of the conflicting application teaches a vaccine comprising of a mRNA encoding a RSV F protein and an LNP.
Claim 20 of the conflicting application teaches a vaccine of claim 1 where the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol.
Claim 35 of the conflicting application teaches the use vaccine of claim 1 to elicit an immune response, the mRNA is comprised of m1ψ, adenosine, cytosine, and guanosine, and the LNP comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid and that the cationic lipid is an ionizable cationic lipid.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
Ciaramella teaches an RSV RNA vaccine that comprises of a mRNA polynucleotide encoding the RSV F protein and an LNP. The structure of the ionizable amino lipid in Ciaramella has the exact structure of the ionizable amino lipid claimed in 199 and 200 of the instant application (Compound 1 of Ciaramella, reproduced below).
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The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 190, 197 – 201, and 208 – 210 of the instant application obvious. While ‘980 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding an RSV antigen can be included with mRNAs encoding antigens from influenza and coronaviruses which are formulated with an LNP. Furthermore, the use of a mRNA encoding the RSV F protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Ciaramella teaches an exact ionizable amino lipid as described in the instant application. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘980 to include the mRNA encoding for RSV with the influenza and SARS-CoV-2 antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
4.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190 – 193, 197 – 201, and 208 – 210 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 8 of U.S. Patent No. US12318443B2 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claim 1 of the conflicting patent teaches a mRNA vaccine comprised of a polynucleotide encoding an influenza virus HA antigen and is formulated in a LNP with 100% of uracil nucleosides in the open reading frame are N1-methylpseudouridine. The LNP has a formula of:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of C1-14 alkyl and C2-14 alkenyl;
R4 is —(CH2)nQ, where Q is —OR, and each n is independently selected from 1, 2, 3, 4, and 5;
each R5 is H;
each R6 is H;
M and M′ are independently selected from —C(O)O—
and —OC(O)—;
R7 is H;
R is H;
R′ is H;
R″ is selected from the group consisting of C3-14 alkyl and C3-14 alkenyl; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Claim 2 of the conflicting patent teaches an ionizable lipid (reproduced below).
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Claim 3 of the conflicting patent teaches a mRNA vaccine of claim 1 where the LNP comprises 20-60 mol % cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % PEG-modified lipid, wherein the LNP comprises 0.5 mol % to 5 mol % PEG-modified lipid.
Claims 4 - 6 of the conflicting patent teaches a mRNA vaccine of claim 1 the HA antigen is an H10 HA antigen, including from the Influenza A H10N8.
Claims 7 – 8 of the conflicting patent teaches the use of the mRNA vaccine of claim 1 to elicit an immune response.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting patent and the instant application significantly overlaps. These claims make claims 190 – 193,197 – 201, and 208 – 210 of the instant application obvious. While ‘443 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding at least one influenza virus antigen can be included with mRNAs encoding antigens from RSV and coronaviruses which are formulated with an LNP. Furthermore, the use of a mRNA encoding the influenza antigen in conjunction with the LNP is discussed in both the application and prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘443 to include the mRNA encoding for the HA antigen of influenza A with other HA influenza antigens, RSV antigens, and SARS-CoV-2 antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
5.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 - 201, and 208 - 210 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10 and 12 -13 of U.S. Patent No. US12453766B2 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claims 1 – 4 of the conflicting patent teaches a mRNA vaccine comprising a polynucleotide encoding a RSV F protein, that is chemically modified to include N1-methylpseudouridine and is formulated in an LNP.
Claim 5 - 10 of the conflicting patent teaches the mRNA vaccine of claim 1 where the LNP comprises 20-60 mol % ionizable cationic lipid, 5-25 mol % neutral lipid, 25-55 mol % sterol, and 0.5-15 mol % polyethylene glycol (PEG)-modified lipid and has a formula of:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of C1-14 alkyl and C2-14 alkenyl;
R4 is-(CH2)nQ, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;
each R5 is H;
each R6 is H;
M and M′ are independently selected from —C(O)O— and —OC(O)—;
R7 is H;
R is H;
R′ is selected from the group consisting of C1-18 alkyl and C2-18 alkenyl;
R″ is selected from the group consisting of C3-14 alkyl and C3-14 alkenyl; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
And the ionizable lipid is:
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Claim 12 and 13 of the conflicting patent teaches the use of a mRNA vaccine to elicit an immune response.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting patent and the instant application significantly overlaps. These claims make claims 190, 197 - 201, and 208 - 210 of the instant application obvious. While ‘766 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding an RSV antigen can be included with mRNAs encoding antigens from influenza and coronaviruses which are formulated with an LNP. Furthermore, the use of a mRNA encoding the RSV F protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘766 to include the mRNA encoding for RSV with the influenza and SARS-CoV-2 antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
6.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 - 200, and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 102 - 114 of U.S. Application No. 17796401 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claims 1 and 102 - 106 of the conflicting application teaches a mRNA vaccine comprising a polynucleotide encoding at least a portion of RSV F protein,
Claims 107 – 112 of the conflicting application teaches a mRNA vaccine with the LNP comprised of any combination of a mixture of lipids that comprises a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable cationic lipid. The molar ratio for the LNP can be 0.5-15 mol% PEG-modified lipid; 5-25 mol% non-cationic lipid; 25-55 mol% sterol; and 20-60 mol% ionizable cationic lipid with claim 25 further limiting the molar ratio to 1-5 mol% PEG-modified lipid; 10-20 mol% non-cationic lipid; 35-45 mol% sterol; and 40-50 mol% ionizable cationic lipid, where the sterol to be cholesterol; and the ionizable cationic lipid has the structure of Compound 1 (reproduced below):
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Claims 113 and 114 of the conflicting application teaches a chemically modified to include N1-methylpseudouridine.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 190, 197 - 200, and 208 – 210 of the instant application obvious. While ‘401 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding an RSV antigen can be included with mRNAs encoding antigens from influenza and coronaviruses which are formulated with an LNP. Furthermore, the use of a mRNA encoding the RSV F protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘401 to include the mRNA encoding for RSV with the influenza and SARS-CoV-2 antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
7.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 – 200, and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 166, 167, 175, and 176 of U.S. Application No. 17797784 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, Joyce, and Ciaramella as discussed above.
Claim 166 of the conflicting application teaches a mRNA vaccine comprising a polynucleotide encoding the RBD and NTD of SARS-CoV-2 spike protein.
Claim 167 of the conflicting application teachesa mRNA vaccine of claim 166 that is chemically modified to include N1-methylpseudouridine
Claim 175 of the conflicting application teachesa mRNA vaccine where the mRNA is formulated with an LNP that comprises a molar ratio of about 20-60 mol% ionizable cationic lipid, 5-25 mol% neutral lipid, 25-55 mol% sterol, and 0.5- 15 mol% PEG-modified lipid.
Claim 176 of the conflicting application teachesa mRNA vaccine the ionizable catonic lipid to comprises:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of C1-14 alkyl and C2-14 alkenyl;
R4 is-(CH2)nQ, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;
each R5 is H;
each R6 is H;
M and M′ are independently selected from —C(O)O— and —OC(O)—;
R7 is H;
R is H;
R′ is selected from the group consisting of C1-18 alkyl and C2-18 alkenyl;
R″ is selected from the group consisting of C3-14 alkyl and C3-14 alkenyl; and
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
Ciaramella teaches an RSV RNA vaccine that comprises of a mRNA polynucleotide encoding the RSV F protein and an LNP. The structure of the ionizable amino lipid in Ciaramella has the exact structure of the ionizable amino lipid claimed in 199 and 200 of the instant application (Compound 1 of Ciaramella, reproduced below).
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The scope of the conflicting application and the instant application significantly overlap. These claims make claims 190, 197 – 200, and 208 – 210 of the instant application obvious. While ‘784 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding a SARS-CoV-2 antigen, including a full length or S1 subunit of the spike protein, can be included with mRNAs encoding antigens from influenza and RSV which are formulated with an LNP. Furthermore, the use a mRNA encoding at least a portion of the SARS-CoV-2 spike protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Ciaramella teaches the exact ionizable amino lipid of the instant application. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘784 to include an mRNA encoding for a full length or a portion of the SARS-CoV-2 spike protein with the influenza and RSV antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
8.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190 – 193, 197 – 200, and 208 – 210 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 5, and 10 of U.S. Patent No. US12329811B2 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claim 1 of the conflicting patent teaches a mRNA vaccine comprising of mRNA encoding three HA proteins from two influenza A virus and one Influenza B virus, three NA proteins from three different influenza viruses (corresponding to the origin virus of the HA proteins) with the polynucleosides comprised of N1-methylpseudouridine, adenosine, guanosine, and cytidine. The mRNA are formulated with an LNP comprised of an ionizable amino lipid, a sterol, a neutral lipid, and a polyethylene glycol (PEG)-modified lipid. The ionizable amino lipid has the formula:
R1 is selected from the group consisting of C5-30 alkyl, C5-20 alkenyl, and —R″M′R′;
R2 and R3 are independently selected from the group consisting of C1-14 alkyl and C2-14 alkenyl;
R4 is —(CH2)nQ, wherein Q is —OR, and n is selected from 1, 2, 3, 4, and 5;
each R5 is H;
each R6 is H;
M and M′ are independently selected from —C(O)O— and —OC(O)—;
R7 is H;
R is H;
R′ is selected from the group consisting of C1-18 alkyl and C2-18 alkenyl;
R″ is selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
m is selected from 5, 6, 7, 8, 9, 10, 11, 12, and 13.
Claims 2 – 4 of the conflicting application teaches the HA and NA proteins being of H1N1, H3N2, and influenza B origin.
Claim 5 of the conflicting application teaches the LNP of the mRNA composition comprising of 40-55 mol % ionizable amino lipid, 30-45 mol % sterol, 5-15 mol % neutral lipid, and 1-5 mol % PEG-modified lipid.
Claim 10 of the conflicting application teaches the ionizable amino lipid of the mRNA composition as:
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The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting patent and the instant application significantly overlap. These claims make claims 190 – 193, 197 – 200, and 208 – 210 of the instant application obvious. While ‘811 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding at least one influenza virus antigen can be included with mRNAs encoding antigens from RSV and coronaviruses which are formulated with an LNP. Furthermore, the use of a mRNA encoding the influenza antigen in conjunction with the LNP is discussed in both the application and prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘811 to include the mRNA encoding for the HA antigen of influenza A with other HA influenza antigens, RSV antigens, and SARS-CoV-2 antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
9.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 – 201, and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 8, 11 -12, 15, 24, and 25 -29 of U.S. Application No. 18569776 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claims 1 – 8, 11 - 12, and 15 of the conflicting application teaches the mRNA of a full length coronavirus spike protein. These claims contain different variations of the spike protein but nonetheless encode for the spike protein.
Claim24 of the conflicting application teaches the mRNA comprising of a chemical modification that may be 1-methylpseudouridine.
Claims 25 - 28 of the conflicting application teaches the mRNA formulated with a LNP that comprises of a combination of a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable amino lipid. The molar ratio of the LNP can be 0.5-15 mol % PEG-modified lipid; 5-25 mol % non-cationic lipid; 25-55 mol % sterol; and 20-60 mol % ionizable amino lipid, with claim 27 further specifying, 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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Claim 29 of the conflicting application teaches the use of mRNA vaccine to elicit an immune response.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 190, 197 – 201, and 208 – 210 of the instant application obvious. While ‘776 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding a SARS-CoV-2 antigen, including a full length or S1 subunit of the spike protein, can be included with mRNAs encoding antigens from influenza and RSV which are formulated with an LNP. Furthermore, the use a mRNA encoding at least a portion of the SARS-CoV-2 spike protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘776 to include an mRNA encoding for a full length or a portion of the SARS-CoV-2 spike protein with the influenza and RSV antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
10.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 – 201, and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4 -7, 13, 19, 25, 31, and 33 - 38 of U.S. Application No. 18028126 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claims 1, 2, 4 -7, 13, 19, 25, and 31 of the conflicting application teaches the mRNA of a full-length coronavirus spike protein formulated with an LNP. These claims contain different variations of the spike protein but nonetheless encode for the spike protein.
Claims 33 and 34 of the conflicting application teaches the mRNA comprising of a chemical modification that may be 1-methylpseudouridine.
Claims 35 - 37 of the conflicting application teaches the mRNA formulated with a LNP that comprises of a combination of a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable amino lipid. The molar ratio of the LNP can be 0.5-15 mol % PEG-modified lipid; 5-25 mol % non-cationic lipid; 25-55 mol % sterol; and 20-60 mol % ionizable amino lipid, with claim 27 further specifying, 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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Claim 38 of the conflicting application teaches the use of mRNA vaccine to elicit an immune response.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlap. These claims make claims 190, 197 – 201, 208 – 210 of the instant application obvious. While ‘126 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding a SARS-CoV-2 antigen, including a full length or S1 subunit of the spike protein, can be included with mRNAs encoding antigens from influenza and RSV which are formulated with an LNP. Furthermore, the use a mRNA encoding at least a portion of the SARS-CoV-2 spike protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘126 to include an mRNA encoding for a full length or a portion of the SARS-CoV-2 spike protein with the influenza and RSV antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
11.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 – 200, and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 10 – 11, 60 – 62, and 64 -73 of U.S. Application No. 18272512 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, and Joyce.
Claim 1, 4, 10 – 11, and 60 - 62 of the conflicting application teaches the mRNA comprised of the RBD and NTD domains of SARS-CoV-2 spike protein.
Claims 64 – 67 of the conflicting application teaches the mRNA comprising of a chemical modification that may be 1-methylpseudouridine
Claim 68 - 72 of the conflicting application teaches the mRNA formulated with a LNP that comprises of a combination of a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable amino lipid. The molar ratio of the LNP can be 40-55 mol % ionizable amino lipid, 30-45 mol % sterol, 5-15 mol % neutral lipid, and 1-5 mol % PEG-modified lipid, with claim 22 further limiting the molar ratio to 40-50 mol % ionizable amino lipid, 35-45 mol % sterol, 10-15 mol % neutral lipid, and 2-4 mol % PEG-modified lipid. Claim 24 and 25 further limit the sterol is cholesterol and the ionizable amino lipid has the structure of Compound 1:
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Claim 73 of the conflicting application teaches the use of mRNA vaccine to elicit an immune response.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlap. These claims make claims 190, 197 – 200, and 208 – 210 of the instant application obvious. While ‘512 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding a SARS-CoV-2 antigen, including a full length or S1 subunit of the spike protein, can be included with mRNAs encoding antigens from influenza and RSV which are formulated with an LNP. Furthermore, the use a mRNA encoding at least a portion of the SARS-CoV-2 spike protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘512 to include an mRNA encoding for a full length or a portion of the SARS-CoV-2 spike protein with the influenza and RSV antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
12.
(Previous rejection, maintained and modified as necessitated by amendments) Claims 190, 197 – 200, and 208 – 210 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55 – 70, and 73 of U.S. Application No. 18272496 in view of Ootsvogels, Nolan, Troup, Sivaramakrishnan, Nagamune, Joyce, and Ciaramella as discussed above.
Claims 55 – 56 and 61 -64 of the conflicting application teaches the mRNA of a at least one full length coronavirus spike protein.
Claims 57 - 60 of the conflicting application teaches the mRNA comprising of a chemical modification that may be 1-methylpseudouridine.
Claims 65 - 70 of the conflicting application teaches the mRNA formulated with a LNP that comprises of a combination of a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable amino lipid. The molar ratio of the LNP can be 40-55 mol % ionizable amino lipid, 30-45 mol % sterol, 5-15 mol % neutral lipid, and 1-5 mol % PEG-modified lipid,. Claim 69 and 70 further limit the sterol is cholesterol and the ionizable amino lipid has the structure of Compound 1:
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Claim 73 of the conflicting application teaches the use of mRNA vaccine to elicit an immune response.
The conflicting claims do not teach a mRNA encoding a fusion protein, wherein the fusion protein encoded by the second ORF does not include an SD1 and/or SD2 domain.
However, as discussed above, Joyce teaches vaccines and binding molecules for the use and treatment of SARS-CoV-2. Joyce teaches nanoparticles comprising of a fusion protein comprising a nanoparticle-forming peptide and at least one antigenic coronavirus peptide (Claim 1). Joyce teaches the antigen can be the RBD and/or NTD of the SARS-CoV-2 spike protein (¶0014).
Regarding claim 208 – 210, Joyce teaches a fusion protein comprising of NTD and RBD and notably lacking the SD1 and SD2 domains (Figure 1E). Joyce teaches the mRNA of the fusion protein as well (¶0017).
As discussed above, Ootsvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent a coronavirus infection along with other viral infections (Abstract). This combination vaccine encodes the mRNA of at least a portion the SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101, ¶0102) and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza and/or RSV fusion protein (Abstract, Claim 1, ¶0003, ¶0014, ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with a preference for all of the uracil nucleotides of the mRNA replaced by m1ψ nucleotide (¶0411), resulting in ORFs comprising of m1ψ, adenosine, guanosine, and cytidine. Ootsvogels further teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein as well as also encoding at least three different influenza virus neuraminidase (NA) protein (Claim 1 – 6, ¶0754). These influenza proteins can be from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10). Furthermore, Ootsvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
Nolan teaches a GGGS linker used in fusion proteins. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Joyce teaches a mRNA encoding a fusion protein lacking a SD1 and/or SD2 domain that encodes a NTD, a RBD, and a linker.
The first, second, and third mRNA taught by Ootsvogels can be formulated in a single LNP or where at least two mRNA are formulated in separate LNPs (Claim 18 and 19) with the LNP comprising 40-50% cationic lipid (Claim 1, ¶1283 and ¶1284), 5-15% neutral lipid (which can be a non-cationic lipid (¶1309)), 20-40% cholesterol (¶1307), and 3% PEG-lipid (¶1299).
Ootsvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlap. These claims make claims 190, 197 – 200, and 208 - 210 of the instant application obvious. While ‘496 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Ootsvogels established that a mRNA encoding a SARS-CoV-2 antigen, including a full length or S1 subunit of the spike protein, can be included with mRNAs encoding antigens from influenza and RSV which are formulated with an LNP. Furthermore, the use a mRNA encoding at least a portion of the SARS-CoV-2 spike protein in conjunction with the LNP and ionizable amino lipid is discussed in both the application and in prior art. Therefore, it would have been prima facie obvious before effective filing date of the claimed invention to have modified the claims of ‘496 to include an mRNA encoding for a full length or a portion of the SARS-CoV-2 spike protein with the influenza and RSV antigens because doing such can lower costs while still effectively treating and/or preventing influenza, RSV, and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
1) Applicant states amendments made to claim 202 overcomes the USC 112 – Indefiniteness, improper Markush group rejection
Applicant has amended claim 202. Examiner has withdrawn the rejection.
2) Applicant states that the amendments made to claim 190 and cancellation of claims 203 – 207 overcome the USC 103 rejection and obviousness-type double patenting rejection
Applicant’s arguments are not persuasive. While Ootsvogels does not teach a mRNA encoding a fusion protein comprising a linker comprising GGGS, as discussed above, Ootsvogels does teach the fusion protein can comprise a linker. Nolan does teach fusion proteins comprising a GGGS linker. Nolan also teaches the purpose of the linker is to decrease the possibility of steric hindrance and maintain or increase bioactivity. Troup, Sivaramakrishnan, and Nagamune teach the selection of a linker protein is a matter of routine optimization. Together, one of ordinary skill in the art would be motivated to optimize the linker between NTD and RBD to increase the likelihood of proper antigen presentation.
Conclusion
NO CLAIMS ARE ALLOWED.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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