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 .
Priority
This is a National Stage Entry under 35 U.S.C. 371 of International Patent Application
No. PCT/US2022/024669, filed April 13, 2022. This application also claims priority to US Provisional Application No. 63242346, filed on September 09, 2022 and US Provisional Application No. 63175007, filed on April, 14, 2021.
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.
Claim 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 . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
• (A) The breadth of the claims;
• (B) The nature of the invention;
• (C) The state of the prior art;
• (D) The level of one of ordinary skill;
• (E) The level of predictability in the art;
• (F) The amount of direction provided by the inventor;
• (G) The existence of working examples; and
• (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The level of skill in the art is high and would include, e.g., Ph.D. level scientists.
Here, the instant claims are broadly drawn to a method for preventing a respiratory infection by administering a mRNA vaccine encoding two mRNA polynucleotides, formulated in at least one LNP, comprising the full length SARS-CoV-2 spike protein and the HA protein of an influenza virus with the polynucleosides consisting of N1-methylpseudouridine, adenosine, guanosine, and cytidine, where the LNP is comprised of 40-50 mol% ionizable amino lipid, 20-40 mol% cholesterol, 5-15 mol% neutral lipid, and 0.5-3 mol% PEG-modified lipid, wherein the ionizable amino lipid has the structure of Formula (I) (See claim 120). In regard for prevention of respiratory virus infection, it is noted that the term “preventing” was interpreted in an absolute sense to mean to always keep something from happening or arising.
As the claims are written, formulation of at least one LNP with any mRNA sequences comprising the full length SARS-CoV-2 spike protein and the HA protein of an influenza virus with the polynucleosides consisting of N1-methylpseudouridine, adenosine, guanosine, and cytidine , where the LNP is comprised of 40-50 mol% ionizable amino lipid, 20-40 mol% cholesterol, 5-15 mol% neutral lipid, and 0.5-3 mol% PEG-modified lipid, wherein the ionizable amino lipid has the structure of Formula (I) (See claim 120) would satisfy claim 120. The claims are not enabled based on, but not limited to, two major lines of evidence. First, not all respiratory virus infections caused by SARS-CoV-2 or Influenza are prevented by mRNA vaccine being claimed. And second, not all respiratory virus infections are caused by SARS-CoV-2 or Influenza alone and therefore a targeted vaccine against SARS-CoV-2 and Influenza would not prevent all respiratory virus infections.
The art establishes that known SARS-CoV-2 vaccines such as BNT162b2 is not 100% effecting in preventing SARS-CoV-2 infection (Polack et al. (NEJM, 2020), Abstract). Similarly, the evidence disclosed in the specification demonstrates that mRNA vaccines satisfying claim 120 can, in some cases, induce an immune response to SARS-CoV-2 antigens (Fig. 7) and/or influenza antigens (Fig. 10, 11) in mice, there is no evidence of prevention SARS-CoV-2 or Influenza virus infection. Additionally, not all mRNA vaccine formulations that satisfy the limitations of claim 120, elicit an immune response to the influenza antigens (Fig.10, 11).
Furthermore, the art establishes that vaccines work by stimulating the body’s immune system to recognize specific viruses, not all viruses (Valich, Health and Medicine, University of Rochester, 2020, Section: “How do RNA vaccines work?). Imamura et al., (Reviews in Medical Virology, 2014) teaches that EV-D68 is a known virus that infects the respiratory system, also known as a respiratory virus infection (Abstract). Therefore, there is reasonable expectation that a vaccine produced to target SARS-CoV-2 and Influenza would not prevent EV-D68 infection.
Together with the evidence discussed above, a combination SARS-CoV-2 and Influenza vaccine that satisfies the limitations of claim 120 would not predictably prevent all respiratory virus infections nor would it reliably prevent infections caused by SARS-CoV-2 and/or Influenza in every single case.
The specification only exemplifies and reduces to practice inducing an immune response following mRNA vaccine administration some cases at certain formulations. However, the specification offers no reasonable direction or working example for the use of an mRNA vaccine that satisfies the limitations of claim 120 prevent all respiratory virus infections.
In view of the foregoing, a vast quantity of experimentation, including expansive clinical trials, would be needed to use the invention based on the content of the disclosure.
Taken together, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these 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.
Claim(s) 108 – 115 and 118 – 119 are rejected under 35 U.S.C. 103 are rejected under 35 U.S.C. 103 as being unpatentable over Oostvogels et al. (US20220211838A1, hereinafter, " Oostvogels "), as evidenced by as evidenced by Daniels et al. (Surveillance report, 2012, hereinafter, “Daniels”).
Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) a coronavirus infection along with other viral infections (Abstract).
Regarding claim 108, Oostvogels 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 (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.
Regarding claim 109, Oostvogels teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein (Claim 1 – 3).
Regarding claim 110, Oostvogels teaches the combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus neuraminidase (NA) protein (Claim 3 – 6, ¶0754).
Regarding claim 111, Oostvogels 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, Oostvogels 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 claims 112 and 113 Oostvogels teaches the first and second mRNA can be formulated in a single LNP or can be formulated in two separate LNPs (Claim 18 and 19).
Regarding claim 114, Oostvogels teaches a LNP comprises 20-60% cationic lipid, 5-25% neutral lipid, 25-55% cholesterol, and 0.5-15% PEG-lipid (Claim 1).
Regarding claim 115, Oostvogels teaches a 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 claims 118 and 119, Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21; see scope of enablement above).
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ product and method they exemplify. As such, the claimed invention is within the scope of Oostvogels, and thus Oostvogels renders the invention prima facie obvious. The rationale to support this conclusion of obviousness is that Oostvogels provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed supplement exhibits any unexpected results compared to 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.
Claims 116 – 117 and 120 – 125 are rejected under 35 U.S.C. 103 as being unpatentable over Oostvogels as applied to claims 108 – 115 and 118 - 119 above, and further in view of Ciaramella et al. (US20190336595A1, hereinafter, “Ciaramella”).
As discussed above, claims 108 - 115 and 118 - 119 were rendered prima facie obvious by the teachings of Oostvogels. The reference fails to teach the exact ionizable amino lipid, a component of LNPs, of claims 116, 117, 120, and 121.
However, Ciaramella teaches an Influenza RNA vaccine that is comprised of a mRNA polynucleotide encoding an HA7 hemagglutinin antigen formulated within a cationic lipid nanoparticle (Claim 1). The structure of the ionizable amino lipid in Ciaramella has the exact structure of the ionizable amino lipid claimed in 116, 117, 120, and 121 of the instant application (Compound 25 of Ciaramella, reproduced below).
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Regarding claims 120, Oostvogels teaches a combination vaccine to elicit a immune response after administration of a combination vaccine (Claim 21) that encodes the mRNA of the full-length SARS-CoV2 spike protein, including the S1 protein (Abstract, Claim 1, ¶0101), and at least one further component of an antigenic peptide or protein from at least one further virus such as influenza (Abstract, Claim 1, ¶0003, ¶0024 ¶0071, ¶806 - ¶808) in at least one LNP (Claim 1) with at least one uracil replaces by N1-methylpseudouridine (m1ψ) nucleotide (¶0411). Oostvogels also teaches a 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 claims 122 and 123, as discussed above, Oostvogels further teaches combination vaccine comprising of mRNA polynucleotides encoding at least three different influenza virus hemagglutinin (HA) protein (Claim 1 – 3) with the HA protein from an H1N1 virus, H3N2 virus, and an influenza B/Victoria lineage virus (¶0748, Table 10).
Regarding claims 124 and 125, Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21; see scope of enablement above).
Oostvogels and Ciaramella are considered to be analogous to the claim invention because they both aim to treat and prevent (see scope of enablement above) respiratory virus infections such as influenza through the use of mRNA vaccines. Oostvogels and Ciaramella teach that the efficacy of the vaccine can change depending on the LNP used in conjunction with the mRNA (Oostvogels ¶1287, ¶1289; Ciaramella ¶0507). 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 and Influenza as taught by Oostvogels 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 and Influenza. 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.
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.
Claims 108 -125 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 190 – 193 and 197 - 207 of copending Application No. 18555087.
Claim 190 of the conflicting application 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, as well as an RSV protein, with the mRNA containing N1-methylpseudouridine, adenosine, guanosine, and cytidine, and where first, second, and third mRNA polynucleotides is formulated in at least one LNP.
Claim 191 of the conflicting application teaches the use of three different influenza virus HA proteins, with claim 192 teaches the further encoding of three different virus NA proteins.
Claim 193 of the conflicting application teaches the three different influenza virus HA proteins are from an H1N1 virus, H3N2 virus, and an influenza B/Victories lineage virus.
Claim 197 of the conflicting application 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 198 of the conflicting application 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 199 of the conflicting application teaches the ionizable lipid structure (reproduced below) where:
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.
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Claim 200 of the conflicting application teaches the exact structure of the ionizable amino lipid (reproduced below).
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Claim 201 of the conflicting application teaches the method of administering the combination vaccine of claim 190 to the subject.
Claim 202 of the conflicting application teaches the method of preventing a respiratory virus infection in a subject by administering the combination vaccine of claim 190 to the subject.
Claim 203 of the conflicting application teaches the use of a combination vaccine comprising of a mRNA encoding an influenza virus HA protein, a full-length SARS-CoV-2 spike protein, and an RSV protein with mRNA containing N1-methylpseudouridine, adenosine, guanosine, and cytidine, and where first, second, and third mRNA polynucleotides is formulated in at least one LNP in a composition comprising 40-50 mol% ionizable amino lipid, 20-40 mol% cholesterol, 5-15 mol% neutral lipid, and 0.5-3 mol% PEG-modified lipid as well as an ionizable amino lipid with a structure as taught in claim 199.
Claim 204 of the conflicting application teaches the structure of the ionizable amino acid as that of claim 200.
Claim 205 of the conflicting application teaches the use of three different influenza virus HA proteins, while claim 206 teaches the three different influenza virus HA proteins are from an H1N1 virus, H3N2 virus, and an influenza B/Victories lineage virus.
Claim 207 of the conflicting application teaches a method of eliciting an immune response in a subject, the method comprising administering the combination vaccine of claim 203 to the subject.
As such, the conflicting claims teach each and every element of the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
2.
Claims 108 - 125 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 Oostvogels.
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.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) above 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting patent and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostvogels established that an mRNA encoding antigens from both influenza and coronaviruses and that these mRNA can be formulated with an LNP. 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 and SARS-CoV-2 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
3.
Claims 108 - 125 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 Oostvogels.
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 teaches a mRNA vaccine of claim 166 that is chemically modified to include N1-methylpseudouridine
Claim 175 of the conflicting application teaches a 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 teaches a 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.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostovogels established that an 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 which are formulated with an LNP. Claim 176 of the conflicting application shares the same LNP composition as the LNP of the instant application which Compound 1 of the instant application falls under. 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 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
4.
Claims 108 - 125 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 Oostvogels.
Claim 1 of the conflicting patent teaches an 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 is 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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As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting patent and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostvogels established that a mRNA encoding at least one influenza virus antigen can be included with mRNAs encoding antigens from coronaviruses which are formulated with an LNP. 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 and SARS-CoV-2 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
5.
Claims 108 - 125 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 Oostvogels.
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.
Claim 24 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.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostvogels 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 which are formulated with an LNP. 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 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
6.
Claims 108 - 125 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 3, 4 -7, 13, 19, 25, 31, and 33 - 38 of U.S. Application No. 18028126 in view of Oostvogels.
Claims 1 – 3, 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.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostvogels 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 which are formulated with an LNP. 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 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7.
Claims 108 - 125 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 Oostvogels.
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.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostvogels 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. 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 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8.
Claims 108 - 125 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 Oostvogels.
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.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
The scope of the conflicting application and the instant application significantly overlaps. These claims make claims 108 - 125 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. Oostvogels 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 which are formulated with an LNP. 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 antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
9.
Claim 108 - 125 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46 of U.S. Application No. 18282097 in view of Oostvogels and Ciaramella as discussed above.
Claim 46 of the conflicting application teaches the mRNA comprised of the RBD and NTD domains of SARS-CoV-2 spike protein, where the mRNA comprising of a chemical modification that may be 1-methylpseudouridine and is formulated with an LNP.
As discussed above, Oostvogels teaches nucleic acid-based combination vaccines for Coronaviridae, Orthomyxoviridae, and Pneumoviridae that can be delivered in a lipid nanoparticle (LNP) to treat or prevent (see scope of enablement) 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 (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. Oostvogels 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, Oostvogels teaches specific HA and NA proteins from well characterized and known H1N1, H3N2, and influenza B/Victoria lineage viruses (Table 8).
The first and second mRNA taught by Oostvogels can be formulated in a single LNP or can be 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).
Oostvogels teaches administering the combination vaccine to elicit an immune response (Claim 21) and a method for administering the combination vaccine to prevent (see scope of enablement) a respiratory virus infection (Abstract, ¶1526).
Ciaramella teaches an Influenza RNA vaccine that is comprised of a mRNA polynucleotide encoding an HA7 hemagglutinin antigen formulated within a cationic lipid nanoparticle (Claim 1). The structure of the ionizable amino lipid in Ciaramella has the exact structure of the ionizable amino lipid claimed in 116, 117, 120, and 121 of the instant application (Compound 25 of Ciaramella, reproduced below).
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The scope of the conflicting application and the instant application significantly overlaps. These claims make claim 108 – 125 of the instant application obvious. While ‘097 does not teach a combination vaccine, the idea of administering vaccines at the same time is well known in the art. Oostvogels 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 of an mRNA encoding at least a portion of the SARS-CoV-2 spike protein in conjunction with the LNP taught by the prior art. As discussed above, 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 ‘097 to include an mRNA encoding for a full length or a portion of the SARS-CoV-2 spike protein with the influenza antigens because doing so can lower costs while still effectively treating and/or preventing influenza and SARS-CoV-2 infection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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