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 .
Interview Summary
Examiner Sifford called Attorney Effler on 5/15/2026 to inform her that the election of group I(a) was non-responsive, and to request an election of the required species. Attorney Effler called Examiner Sifford on 5/19/2026 and left a voice message that Applicant wished to elect SEQ ID NOs: 7 and 9 (for H1 and H10, respectively), and to change the election of ferritin to a bacterial species of ferritin, to fit the other species elections.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 95-117, and the species of (a) a distinct set of encoded immunogens: the combination of subtype H1 (Group 1) and subtype H10 (Group 2), and (b) chemically modified mRNA: N1-methylpseudouridine, in the reply filed on 5/8/2026 is acknowledged.
Claims 118 and 119 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/8/2026.
Applicant's election with traverse of the required species, I(a): SEQ ID NOs: 7 and 9 (for H1 and H10, respectively) in the interview on 5/15/2026 is acknowledged. The traversal is on the ground(s) that nowhere does 37 C.F.R. §1.146 or MPEP §806.04 require Applicant to amend or narrow the claims to include elements that are not already present in the pending claims. The election of species is to the claims as written and does not require Applicant to introduce unclaimed features in order to comply with the election of species. This is not found persuasive because: Applicant cannot ignore a requirement. MPEP section 809.02(a). Election of species can be required even if the claims do not recite something. Even though there are no sequences in the claims, you must elect, even if the claims are generic. The election of species requirement did not ask Applicant to amend or narrow claims at all. Amending claims is not required to make this election. The examiner is able to require election of species even from a generic claim. Furthermore, there actually are species claims, where the claims recite "one or a distinct set of encoded immunogens," so in some instances there are more than one species (like from Group 1 or 2) already present in the claims.
The requirement is still deemed proper and is therefore made FINAL.
Claim 100 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/15/2026.
Claims 95-99 and 101-117 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 5/11/2026, 4/30/2024, and 9/22/2023 are in compliance with 37 CFR 1.97. Accordingly, the references listed in the IDSs are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 102 and 103 are objected to because of the following informalities: claims 102 and 103 recite redundant subtypes, (claim 102: subtype H1 is present in (i) and (ii); claim 103: subtype H3 is present in (i) and (ii), and subtype H10 is present in (i), (ii), and (iii). Appropriate correction is required.
Claim 109 is objected to because of the following informalities: claim 109 recites “wherein at least one of the two or more sequences that encode an influenza HA stem polypeptide are derived from influenza A Group I and influenza A Group 2” on lines 2-4. To put the claim in better form, it should recite “wherein the two or more coding sequences that encode an influenza HA stem polypeptide derived from Group 1 and Group 2”. Appropriate correction is required.
Claim 113 is objected to because of the following informalities: claim 113 recites “wherein the mRNA comprises at least one chemical modification selected from pseudouridine [..]”. The examiner suggests replacing “selected from” with “selected from the group consisting of:” on line 2. Appropriate correction is required.
Claim 117 is objected to because of the following informalities: claim 117 recites “the RNA of claim 95”, instead of “the mRNA of claim 95.” Appropriate correction is required.
Claim Interpretation
The specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (spec., p. 17, lines 32-36).
The specification describes “carrier” as “a range of carrier systems have been described which encapsulate or complex mRNA in order to facilitate mRNA delivery and consequent expression of encoded antigens as compared to mRNA which is not encapsulated or complexed” (spec. p. 42).
The specification defines lipid nanoparticles (LNPs) as non-virion liposome particles in which mRNA can be encapsulated (p. 42).
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.
Written Description
Claims 95-99 and 101-117 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims above are drawn to a genus of carrier-formulated mRNAs comprising at least one coding sequence encoding an influenza HA stem polypeptide (claim 95). Other embodiments of the claims require the carrier to be a lipid nanoparticle (LNP; claim 96), with particular composition (claims 97-99), or for the mRNA to comprise at least one additional coding sequence encoding a ferritin protein nanoparticle (claim 99). Other claims require the influenza HA stem polypeptide to be derived from members of influenza A Group 1 or Group 2 (claims 101-103), the stem to be of particular length (claim 104), or the mRNA to comprise two or more coding sequences each encoding an influenza HA stem polypeptide, or more specifically the influenza HA stem polypeptide being derived from specific Groups or strains (claims 105-112). Additional embodiments require the carrier-formulated mRNA to comprise a chemical modification of N1-methylpseudouridine (claim 113), be self-replicating (claim 114) or are drawn to a vaccine, kit, or immunogenic composition comprising the mRNA and a pharmaceutical acceptable carrier (claims 115-117).
The specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (spec., p. 17, lines 32-36). These immunogenic fragments and variants must be described with a representative amount of species since there is no conserved structure required among all members of the genus.
Even if the prior art or instant disclosure are aware of examples of such influenza HA stem polypeptides, the totality of known influenza HA stem polypeptides would not be representative of the entire genus for the reasons discussed below.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
Furthermore, to satisfy the written description requirement for the genus carrier-formulated mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide, Applicant must adequately describe representative vectors to reflect the structural diversity of the claimed genus. See Eli Lilly, 119 F.3d at 1568 (“[N]aming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993) (“Claiming all DNA[s] that achieve a result without defining what means will do so is not in compliance with the description requirement; it is an attempt to preempt the future before it has arrived.”).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. As stated above, no conserved structure is required among all members of the genus and so a representative amount of species must be disclosed. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, as here in which influenza HA stem polypeptides can be immunogenic fragment or variant of an influenza HA stem region. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” One of skill in this art cannot envision the structure of every influenza HA stem polypeptide. The specification indicates that the HA stem is highly conserved and broadly neutralizing antibodies against influenza virus recognize the HA stem, and that the use of ferritin self-assembling nanoparticles can present stabilized HA stem trimers (spec., p. 2). Additionally, the specification encompasses HA stem polypeptides derived from various influenza subtypes (spec. p. 8), particular strains (spec., p. 13), and several recombinant polypeptides that comprise HA stems (spec., pp. 13-14). Thus, the specification provides a number of examples of HA stem polypeptides. However, the provided species are not representative of the very broad genus of HA stem polypeptides, and variants and fragments thereof in particular, encompassed by the claims. Therefore, since limited species are provided to represent these genera, the claims encompassing the same clearly fail the written description requirement.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
The specification describes a number of “Influenza HA stem polypeptides”, including the polypeptide sequences of HA stem from A/New/Caledonia/20/1999 (H1N1), A/Michigan/45/2015 (H1N1), A/Finland/486/2004 (H3N2), A/Jiangxi/IPB13/2013 (H10N8) strains, as well as these fused to H. pylori ferritin (spec., pp. 13-14). However, the genus is far broader than such limited disclosure.
“Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. Since each genus recited in the instant claims is large, it would be very challenging to describe sufficient species to cover the structures of the entire genus. Several species is certainly not adequate. The disclosure does not provide examples of other influenza HA stem variants with fusion proteins beyond ferritin.
Overall, at the time the invention was made, the level of skill for preparing carrier-formulated mRNAs and influenza HA stem polypeptides was high.
A representative number of species has not been taught to describe these genera; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of carrier-formulated mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
While applicant has described a few species within each of the genera recited, and the art may provide more, the genus is large and would encompass structures that cannot be visualized from the prior art or instant disclosure. One of skill in this art cannot determine the structures encompassed by the claimed genera only defined by function. Any future influenza HA stem structure may or may not be encompassed, and if it is, it would not have been represented in Applicant’s disclosed species. Thus, the described species cannot be considered representative of the recited genera of carrier-formulated mRNAs comprising at least one coding sequence encoding an influenza HA stem polypeptide. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, the claims are rejected here.
As discussed above, an applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613. Therefore, it is recommended that the instant claims be amended to recite complete structural information of the claimed carrier-formulated mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 95-96, 101-103, and 115-117 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
The claims recite: a carrier-formulated mRNAs comprising at least one coding sequence encoding an influenza HA stem polypeptide (claim 95). Other embodiments of the claims require the carrier to be a lipid nanoparticle (LNP; claim 96). Other claims require the influenza HA stem polypeptide to be derived from members of influenza A Group 1 or Group 2 (claims 101-103). Additional embodiments encompass an immunogenic composition, vaccine, or kit, comprising the carrier-formulated mRNA (claims 115-117).
The specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (spec., p. 17, lines 32-36); “carrier” as “a range of carrier systems have been described which encapsulate or complex mRNA in order to facilitate mRNA delivery and consequent expression of encoded antigens as compared to mRNA which is not encapsulated or complexed” (spec. p. 42); and “lipid nanoparticles” (LNPs) as non-virion liposome particles in which mRNA can be encapsulated (p. 42).
Based on this guidance from the specification, the examiner is interpreting the claim limitation “carrier” and “lipid nanoparticles” to encompass cells that possess influenza viral genomes which encode the full-length HA gene, during the course of natural infection, these genome segments will be transcribed into mRNA that encodes the HA stem protein. In such cells, the mRNA are “carrier-formulated” since it is mixed with at least water. Thus, all claims rejected above read on a judicial exception.
The claims do not incorporate the exception into a practical application because no application is required, such as method steps, in product claims. Thus, we must look at markedly different characteristics compared to the natural product. The claims 95-96, 101-103, and 116-117 fail to add these because they do not appear to require any structural elements beyond the influenza-infected cell.
Therefore, we must look for additional elements that amount to significantly more. Claims 95-96, 101-103, and 116-117 do not add additional elements. The “vaccine” and “kit” of claims 116 and 117 do not appear to require any additional structural elements beyond the influenza-infected cell. Claim 115 requires the additional element of at least one pharmaceutically acceptable carrier, which is not defined by the specification. In determining whether this additional element is sufficient to amount to significantly more than the judicial exception, consideration must be made to what “pharmaceutically acceptable carrier” encompasses. Claim 115 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because an influenza infected cell comprises buffered water, which under the broad reasonable of interpretation, is a “pharmaceutically acceptable carrier”. Accordingly, the additional element of claim 115 is well-understood, routine, and conventional.
Therefore, claims 95-96, 101-103, and 115-117 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 95-96, 98, 99, 101-106, 113 and 115-116 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ciaramella, et al. (PGPub US 20180311336 A1, published 11/1/2018).
The Prior Art
Ciaramella discloses influenza ribonucleic acid vaccines, methods of using the vaccines, and compositions comprising the vaccines (Abstract). The vaccine may comprise at least one mRNA having an open reading frame encoding HA protein, or an immunogenic fragment thereof (para. [0014]), from any one or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and H18 (paras. [0015]-[0018]; these include Group 1 and Group 2 influenza). Ciaramella also specifically discloses that the vaccine may comprise at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza HA2 stem antigen (para. [0219]), including stem antigens that are within 130 to 400 residues in length (Table 16). Ciaramella discloses that mRNA encoding HA protein sequences, such as HA stem sequences from different strains, have been demonstrated to induce serum antibodies that bind to a diverse panel of recombinant HA proteins (para. [0228]). Ciaramella further discloses vaccines that comprises an mRNA encoding H1 or H3 subtype consensus HA antigens with ferritin fusion sequences (para. [0213]; Table 1; Fig. 12B), and a number of other HA sequences with ferritin for particle formation (Tables 17 and 21).
Ciaramella also discloses that lipid nanoparticle (LNP) formulations significantly enhance the effectiveness of mRNA vaccines, including chemically modified and unmodified mRNA vaccines (para. [0226]). The chemical modification may be N1-methylpseudouridine (para. [0038]). The LNP may comprise an ionizable cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid (para. [0381]). The cationic lipid may be an ionizable cationic lipid (as required by claim 98).
Ciaramella also discloses that the vaccine may comprise the RNA polynucleotide having an open reading frame encoding a hemagglutinin protein and a pharmaceutically acceptable carrier or excipient (para. [0126]).
As discussed in the claim interpretation section above, the specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (instant specification, p. 17, lines 32-36). The broadest reasonable interpretation to the limitation “comprising at least one coding sequence encoding an influenza HA stem polypeptide” does not appear to exclude a full length HA protein, which is encompassed by the teachings of Ciaramella.
Therefore, claims 95-96, 98, 99, 101-106, 113 and 115-116 are anticipated by Ciaramella.
Claims 95-96, 101-103, 113, and 115-117 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hoge, et al. (WO2019036670A2, published 2/21/2019).
The claimed invention encompasses a carrier-formulated mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide, as recited in claim 95.
The Prior Art
Hoge teaches mRNA vaccines formulated in a carrier, wherein the mRNA encodes an antigen (Abstract). Hoge specifically discloses modified mRNA encoding the hemagglutinin of H10N8 Influenza A (p. 103, para. 2), or in other embodiments the hemagglutinin protein is H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18, or a fragment thereof, which may not comprise a head domain, or is otherwise truncated (p. 24, para. 2). Therefore, a person having ordinary skill in the art would immediately envision using the full-length HA which comprises the stem. The instant specification indicates that Group 1 influenza A encompasses H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17 and/or H18 (spec., p. 6), and Group 2 influenza A encompasses H3, H4, H7, H10, H14, and H15 (spec., p. 6).
Hoge further discloses that its vaccine is formulated in a lipid nanoparticle (LNP), which enables the delivery of chemically modified or unmodified mRNA vaccines (p. 44, last para.). Hoge discloses a number of components for its LNPs, including the base formula of an ionizable lipid, a structural lipid, a phospholipid, and mRNA (p. 45, para. 3). Hoge teaches that the ionizable lipid is an ionizable amino or cationic lipid, the phospholipid is a neutral lipid, and the structural lipid is cholesterol, or more specifically ionizable lipid:cholesterol:DSPC:PEG2000-DMG at a molar ratio of 50:38.5:10:1.5 (p. 45, para. 3). Notably, DSPC is a non-cationic lipid (spec., p. 4).
Hoge also discloses that chemical modification of mRNAs can facilitate certain desirable properties of vaccines of the invention, such as reducing unwanted innate immune responses against mRNA components or facilitate desirable levels of protein expression of the antigen or antigens of interest (pp. 26-27, bridging para.). Hoge specifically discloses that 1-methylpseduouridine (sic) is a modification of mRNA polynucleotides useful in its compositions (pp. 30 and 33).
Hoge teaches that in addition to LNPs, the mRNA vaccine may be formulated in other carriers, including known carriers, including but not limited to non-LNP lipid based carriers, peptide carriers, conjugates, etc. (p. 73, para. 2). Additionally, the lipid composition of a pharmaceutical composition can include one or more components in addition, for example, one or more permeability enhancer molecules, carbohydrates, surface altering agents, or other components (p. 68, para. 1).
Additionally, Hoge discloses kits for the selection design, and/or utilization of the mRNA vaccines (p. 13, para. 3).
As discussed in the claim interpretation section above, the specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (spec., p. 17, lines 32-36). The broadest reasonable interpretation to the limitation “comprising at least one coding sequence encoding an influenza HA stem polypeptide” does not appear to exclude a full length HA protein, an HA lacking the head domain, or truncations of HA, which are disclosed by Hoge.
Therefore, claims 95-96, 101-103, 113, and 115-117 are anticipated by Hoge.
Claims 95-96, 98, 101-103, 105-110, and 114-116 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bertholet Girardin, et al. (WO 2020035609 A2, published 2/20/2020).
The Prior Art
Bertholet Girardin discloses immunogenic or pharmaceutical compositions comprising self-replicating mRNA molecules that encode influenza virus antigens for treating and/or preventing influenza infections (Abstract; p. 4, lines 29-37). Bertholet Girardin also discloses that the SAM vaccines can be encapsulated in lipid-nano particles (LNPs; p. 4, lines 29-37). SAM vaccines are self-amplifying RNAs (p. 4, last para.). Additionally, Bertholet Girardin discloses that LNP delivery systems may comprise neutral lipids, cationic lipids, cholesterol, and PEGylated lipids (p. 22). Bertholet Girardin also specifically discloses that a mixture of DSPC, DLinDMA, PEG-DMG, and cholesterol is particularly effective (p. 22, lines 23-24). The instant specification indicates that DlinDMA is an ionizable cationic lipid (pp. 42-43). Notably, DSPC is a non-cationic lipid (spec., p. 4). More specifically, some of the immunogenic compositions disclosed by Bertholet Girardin comprise (i) a first self-replicating RNA molecule encoding a polypeptide comprising a first antigen and (ii) a second self-replicating RNA molecule encoding a polypeptide comprising a second antigen, wherein the first and second antigens are both from influenza virus but the first antigen is from a different strain of influenza virus to the second antigen (p. 2, lines 5-9). Bertholet Girardin also specifically discloses the first and/or second antigen is hemagglutinin, which may be derived from H1, H2, H5, H6, H7, H9, or H10, and the immunogenic composition may comprise a first and second antigens that are HA derived from H1+H3, and other combinations of antigens from influenza virus are envisaged (p. 15, paras. 3-5). Therefore, a person having ordinary skill in the art would immediately envision using the full-length HA which comprises the stem. Additionally, Bertholet Girardin discloses multivalent vaccines, such as a bicistronic SAM construct harboring two HA genes, H5 and H1, wherein the second HA gene is cloned downstream of a 2A-driven sequence (p. 55, lines 11-13; Fig. 1a), which are encapsulated in lipid nanoparticles (p. 4, last para.). Additionally, Bertholet Girardin discloses that the vaccine compositions may also comprise a pharmaceutically acceptable carrier (p. 44, paras. 2-3).
As discussed in the claim interpretation section above, the specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (instant specification, p. 17, lines 32-36). The broadest reasonable interpretation to the limitation “comprising at least one coding sequence encoding an influenza HA stem polypeptide” does not appear to exclude a full length HA protein, which is disclosed by Bertholet Girardin.
Therefore, claims 95-96, 98, 101-103, 105-110, and 114-116 are anticipated by Bertholet Girardin.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 95-99 and 101-117 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella, et al. (PGPub US 20180311336 A1, published 11/1/2018) in view of Hoge, et al. (WO2019036670A2, published 2/21/2019) as evidenced by Anderluzzi, et al. (Vaccines (Basel). 2020 May 8;8(2):212. doi: 10.3390/vaccines8020212. PMID: 32397231), and Bertholet Girardin, et al. (WO 2020035609 A2, published 2/20/2020).
The Prior Art
Ciaramella discloses influenza ribonucleic acid vaccines, methods of using the vaccines, and compositions comprising the vaccines (Abstract). The vaccine may comprise at least one mRNA having an open reading frame encoding HA protein, or an immunogenic fragment thereof (para. [0014]), from any one or a combination of any or all of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and H18 (paras. [0015]-[0018]; these include Group 1 and Group 2 influenza). Ciaramella also specifically discloses that the vaccine may comprise at least one RNA (e.g., mRNA) polynucleotide having an open reading frame encoding at least one influenza HA2 stem antigen (para. [0219]), including stem antigens that are within 130 to 400 residues in length (Table 16). Ciaramella discloses that mRNA encoding HA protein sequences, such as HA stem sequences from different strains, have been demonstrated to induce serum antibodies that bind to a diverse panel of recombinant HA proteins (para. [0228]). Ciaramella further discloses vaccines that comprises an mRNA encoding H1 or H3 subtype consensus HA antigens with ferritin fusion sequences (para. [0213]; Table 1; Fig. 12B), and a number of other HA sequences with ferritin for particle formation (Tables 17 and 21).
Ciaramella also discloses that lipid nanoparticle (LNP) formulations significantly enhance the effectiveness of mRNA vaccines, including chemically modified and unmodified mRNA vaccines (para. [0226]). The chemical modification may be N1-methylpseudouridine (para. [0038]). The LNP may comprise an ionizable cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid (para. [0381]). The cationic lipid may be an ionizable cationic lipid (as required by claim 98).
Ciaramella also discloses that the vaccine may comprise the RNA polynucleotide having an open reading frame encoding a hemagglutinin protein and a pharmaceutically acceptable carrier or excipient (para. [0126]).
As discussed in the claim interpretation section above, the specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (instant specification, p. 17, lines 32-36). The broadest reasonable interpretation to the limitation “comprising at least one coding sequence encoding an influenza HA stem polypeptide” does not appear to exclude a full length HA protein, which is encompassed by the teachings of Ciaramella.
However, Ciaramella does not disclose a carrier formulated-formulated mRNA, wherein the carrier is a lipid nanoparticle (LNP) and the LNP comprises a PEG-modified lipid, a non-cationic lipid, a sterol, and a non-ionisable cationic lipid (claim 97).
Hoge teaches mRNA vaccines formulated in a carrier, wherein the mRNA encodes an antigen (Abstract). Hoge specifically discloses modified mRNA encoding the hemagglutinin of H10N8 Influenza A (p. 103, para. 2), or in other embodiments the hemagglutinin protein is H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18, or a fragment thereof, which may not comprise a head domain, or is otherwise truncated (p. 24, para. 2). Therefore, a person having ordinary skill in the art would immediately envision using the full-length HA which comprises the stem. The instant specification indicates that Group 1 influenza A encompasses H1, H2, H5, H6, H8, H9, H11, H12, H13, H16, H17 and/or H18 (spec., p. 6), and Group 2 influenza A encompasses H3, H4, H7, H10, H14, and H15 (spec., p. 6).
Hoge further discloses that its vaccine is formulated in a lipid nanoparticle (LNP), which enables the delivery of chemically modified or unmodified mRNA vaccines (p. 44, last para.). Hoge discloses a number of components for its LNPs, including the base formula of an ionizable lipid, a structural lipid, a phospholipid, and mRNA (p. 45, para. 3). Hoge teaches that the ionizable lipid is an ionizable amino or cationic lipid, the phospholipid is a neutral lipid, and the structural lipid is cholesterol, or more specifically ionizable lipid:cholesterol:DSPC:PEG2000-DMG at a molar ratio of 50:38.5:10:1.5 (p. 45, para. 3). Notably, DSPC is a non-cationic lipid (spec., p. 4).
Hoge also discloses that chemical modification of mRNAs can facilitate certain desirable properties of vaccines of the invention, such as reducing unwanted innate immune responses against mRNA components or facilitate desirable levels of protein expression of the antigen or antigens of interest (pp. 26-27, bridging para.). Hoge specifically discloses that 1-methylpseduouridine (sic) is a modification of mRNA polynucleotides useful in its compositions (pp. 30 and 33).
Hoge teaches that in addition to LNPs, the mRNA vaccine may be formulated in other carriers, including known carriers, including but not limited to non-LNP lipid based carriers, peptide carriers, conjugates, etc. (p. 73, para. 2). Additionally, the lipid composition of a pharmaceutical composition can include one or more components in addition, for example, one or more permeability enhancer molecules, carbohydrates, surface altering agents, or other components (p. 68, para. 1).
Additionally, Hoge discloses kits for the selection design, and/or utilization of the mRNA vaccines (p. 13, para. 3).
As discussed in the claim interpretation section above, the specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (spec., p. 17, lines 32-36). The broadest reasonable interpretation to the limitation “comprising at least one coding sequence encoding an influenza HA stem polypeptide” does not appear to exclude a full length HA protein, an HA lacking the head domain, or truncations of HA, which are disclosed by Hoge.
Hoge also discloses that oil-in-water emulsions ideally include one or more cationic molecules to provide a positively charged droplet surface to which negatively-charged mRNA can attach, and one such useful cationic lipid is 1,2-dioleoyloxy-3-(trimethylammonio)propane (DOTAP) (p. 74). Anderluzzi provides evidence that DOTAP is a non-ionizable cationic lipid (Abstract).
It would have been obvious to one of ordinary skill in the art to modify the LNP-formulated mRNA comprising at least one coding sequence encoding an influenza HA stem polypeptide such that the LNP comprises a PEG-modified lipid, a non-cationic lipid, a sterol, and a non-ionisable cationic lipid. Hoge discloses that DOTAP may be useful to provide a positively charge to which negatively-charged mRNA can attach, and Ciaramella and Hoge teach that LNPs may comprise a PEG-modified lipid, a non-cationic lipid, and a sterol. One of ordinary skill in the art would have been motivated to provide a positive charge to which negatively-charged mRNA can attach. There would be a reasonable expectation of success because Hoge discloses the suitability of DOTAP in lipid compositions to provide a positive charge to which negatively-charged mRNA can attach.
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem, and the prior art teaches that parameter magnitudes that are encompassed by instant claims, often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art.
Thus a lipid nanoparticle constructed of a PEG-modified lipid, a non-cationic lipid, a sterol, and a non-ionisable cationic lipid and containing mRNA encoding an influenza HA stem polypeptide is obvious as all particle components are used in the art for the same purpose, a reasonable expectation of success is had that they will form a functional particle for mRNA delivery since they are part of its prior-art recognized optional ingredients. The amount of each is a result effective variable which will be arrived at by routine experimentation.
It would have been further obvious to provide the carrier-formulated mRNAs in a kit, as Hoge discloses kits for the selection design, and/or utilization of the mRNA vaccines (p. 13, para. 3). One of ordinary skill in the art would have been motivated to utilize the mRNA vaccines, and there would have been a reasonable expectation of success because Hoge discloses carrier-formulated mRNA vaccines in kits for that purpose.
Therefore, claims 95-99, 101-106, 113, and 115-117 were prima facie obvious before the priority date of the instant invention.
Regarding claims 107-112 and 114, Ciaramella and Hoge as evidenced by Anderluzzi do not disclose a carrier-formulated mRNA that comprises two or more coding sequences each encoding an influenza HA stem polypeptide, wherein the coding sequences are derived from influenza A Group 1 and/or influenza A Group 2, wherein at least one of the two or more coding sequences that encode an influenza HA stem polypeptide are derived from influenza A Group 1 and influenza A Group 2, or specifically wherein the influenza A Group 1 comprises subtype H1 and/or Group 2 comprises subtype H10. Nor do they teach the carrier-formulated mRNA, wherein the mRNA is self-replicating.
Bertholet Girardin discloses immunogenic or pharmaceutical compositions comprising self-replicating mRNA molecules that encode influenza virus antigens for treating and/or preventing influenza infections (Abstract; p. 4, lines 29-37). Bertholet Girardin also discloses that the SAM vaccines can be encapsulated in lipid-nano particles (LNPs; p. 4, lines 29-37). SAM vaccines are self-amplifying RNAs (p. 4, last para.). Additionally, Bertholet Girardin discloses that LNP delivery systems may comprise neutral lipids, cationic lipids, cholesterol, and PEGylated lipids (p. 22). Bertholet Girardin also specifically discloses that a mixture of DSPC, DLinDMA, PEG-DMG, and cholesterol is particularly effective (p. 22, lines 23-24). The instant specification indicates that DlinDMA is an ionizable cationic lipid (pp. 42-43). Notably, DSPC is a non-cationic lipid (spec., p. 4). More specifically, some of the immunogenic compositions disclosed by Bertholet Girardin comprise (i) a first self-replicating RNA molecule encoding a polypeptide comprising a first antigen and (ii) a second self-replicating RNA molecule encoding a polypeptide comprising a second antigen, wherein the first and second antigens are both from influenza virus but the first antigen is from a different strain of influenza virus to the second antigen (p. 2, lines 5-9). Bertholet Girardin also specifically discloses the first and/or second antigen is hemagglutinin, which may be derived from H1, H2, H5, H6, H7, H9, or H10, and the immunogenic composition may comprise a first and second antigens that are HA derived from H1+H3, and other combinations of antigens from influenza virus are envisaged (p. 15, paras. 3-5). Therefore, a person having ordinary skill in the art would immediately envision using the full-length HA which comprises the stem. Additionally, Bertholet Girardin discloses multivalent vaccines, such as a bicistronic SAM construct harboring two HA genes, H5 and H1, wherein the second HA gene is cloned downstream of a 2A-driven sequence (p. 55, lines 11-13; Fig. 1a), which are encapsulated in lipid nanoparticles (p. 4, last para.). Additionally, Bertholet Girardin discloses that the vaccine compositions may also comprise a pharmaceutically acceptable carrier (p. 44, paras. 2-3).
As discussed in the claim interpretation section above, the specification defines an “influenza HA stem polypeptide” to be a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region” (instant specification, p. 17, lines 32-36). The broadest reasonable interpretation to the limitation “comprising at least one coding sequence encoding an influenza HA stem polypeptide” does not appear to exclude a full length HA protein, which is disclosed by Bertholet Girardin.
Accordingly, it would have been obvious to one of ordinary skill in the art to modify the mRNA vaccines comprising a carrier and mRNA comprising two or more coding sequences each encoding an influenza HA stem polypeptide, wherein the coding sequences are on the same RNA molecule, and the two or more coding sequences encode different influenza HA stem polypeptides rendered obvious by Ciaramella and Hoge as evidenced by Anderluzzi, such that the HA stem polypeptides are derived from influenza A Group 1 and influenza A Group 2, because Bertholet Girardin discloses such combinations, including H1 (Group 1) and H3 (Group 2). Additionally, it would have been obvious to one of ordinary skill in the art wherein the Group 1 subtype is H1 and the Group 2 subtype is H10, because Ciaramella, Hoge, and Bertholet Girardin each disclose vaccines that encode HA from subtype H10, and Bertholet Girardin discloses vaccines encoding two different HAs on the same bicistronic vector. It also would have been obvious to one of ordinary skill in the art to utilize a self-replicating carrier-formulated mRNA vaccine comprising at least one coding sequence encoding an influenza HA stem polypeptide, because Bertholet Girardin teaches self-replicating mRNA vaccines encoding HA polypeptides. One of ordinary skill in the art would have been motivated to vaccinate against those influenza subtypes. There would have been a reasonable expectation of success because Bertholet Girardin teaches bicistronic self-amplifying mRNA vectors encoding HA proteins and their use as immunogenic compositions. Therefore, claims 95-99 and 101-117 were prima facie obvious before the priority date of the instant invention.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 95, 96, 115, and 117 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 117-118, 131, and 133 of copending Application No. 18/283,601 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 95-99 and 101-117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-125 and 130-133 of copending Application No. 18/283,601 (published as PGPub US 20240181037 A1) in view of Ciaramella, et al. (PGPub US 20180311336 A1, published 11/1/2018), Hoge, et al. (WO2019036670A2, published 2/21/2019) as evidenced by Anderluzzi, et al. (Vaccines (Basel). 2020 May 8;8(2):212. doi: 10.3390/vaccines8020212. PMID: 32397231), and Bertholet Girardin, et al. (WO 2020035609 A2, published 2/20/2020).
The instant and reference application claims each encompass identical claims, as pointed out in the statutory double patenting rejection (instant claims 95, 96, 115, and 117 are identical to reference claims 117-118, and 131, and 133). Additionally, each set of claims encompasses the LNP comprising a PEG-modified lipid, a non-cationic lipid, a sterol, and an ionizable cationic lipid (instant claim 98, reference claim 119). Additionally, each encompasses an mRNA that comprises at least one additional coding sequence which encodes a protein nanoparticle that is ferritin (instant claim 99, reference claim 120), the influenza HA stem polypeptide derived from influenza A Group I, or specifically subtype H1 (instant claims 101-102, reference claim 122) or influenza A Group 2, or specifically subtype H10 (instant claims 101 and 103, reference claim 123). Each set of claims also encompasses the mRNA comprising a chemical modification that is N1-methylpseudouridine (instant claim 113, reference claim 130), and immunogenic compositions, vaccines, or kits comprising the mRNA (instant claims 115-117, reference claims 131-133).
Notably, the applications differ in that while the instant claims include embodiments wherein two or more coding sequences each encoding an HA stem polypeptide are encoded on the same mRNA molecule (instant claim 105-112), the reference application instead requires two or more coding sequences each encoding an influenza HA stem polypeptide are encoded on separate mRNA molecules (reference claims 124-125). The applications also differ in that instant claim 104 requires particular lengths for the HA stem polypeptide, whereas the reference application contains no such embodiment. Furthermore, the applications differ in that the instant claim 97 requires the LNP to comprise a PEG-modified lipid, a non-cationic lipid, a sterol, and a non-ionisable cationic lipid, whereas the reference claims do not have such an embodiment. The applications also differ in that instant claim 114 requires the mRNA to be self-replicating, whereas the reference claims do not include such an embodiment.
However, as discussed in the rejection under 35 U.S.C. §103 above, the instant claims 97 and 105-112 are rendered obvious by the references Ciaramella, Hoge as evidenced by Anderluzzi, and Bertholet Girardin.
It would have been obvious to modify the reference claims with the teachings of Ciaramella, Hoge as evidenced by Anderluzzi, and Bertholet Girardin to come upon the instant claims 97 and 105-112. As described above in the rejection under 35 U.S.C. §103, a lipid nanoparticle constructed of a PEG-modified lipid, a non-cationic lipid, a sterol, and a non-ionisable cationic lipid and containing mRNA encoding an influenza HA stem polypeptide is obvious as all particle components are used in the art for the same purpose, a reasonable expectation of success is had that they will form a functional particle for mRNA delivery since they are part of its prior-art recognized optional ingredients. The amount of each is a result effective variable which will be arrived at by routine experimentation. Ciaramella discloses influenza HA stems within the length of 130 to 400 residues. Bertholet Girardin discloses bicistronic self-replicating bicistronic vectors encoding different Group 1 and Group 2 HAs. One of ordinary skill in the art would have been motivated to make or use influenza vaccines. There would have been a reasonable expectation of success because similar compositions and their use are known in the cited references. Accordingly, instant claims 95-99 and 101-117 were prima facie obvious to one of ordinary skill in the art.
This is a provisional nonstatutory double patenting rejection.
Claims 95-99 and 101-117 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 15-16, and 21 of U.S. Patent No. 12606596 B2 in view of Ciaramella, et al. (PGPub US 20180311336 A1, published 11/1/2018), Hoge, et al. (WO2019036670A2, published 2/21/2019) as evidenced by Anderluzzi, et al. (Vaccines (Basel). 2020 May 8;8(2):212. doi: 10.3390/vaccines8020212. PMID: 32397231), and Bertholet Girardin, et al. (WO 2020035609 A2, published 2/20/2020).
The instant and ‘596 claims each encompass mRNA molecules encoding first and second influenza HA stem proteins that are from two different strains (instant claims 105-112, ‘596 claims 1, 7, 9-11, and 15-16). While the instant claim 99 requires the mRNA comprises at least one additional coding sequence which encodes a protein nanoparticle, ferritin, the ‘596 claims are each drawn to ferritin and fusion proteins thereof that can self-assemble to form a nanoparticle (‘596 claim 2). Additionally, each set of claims encompasses immunogenic compositions comprising the mRNA and a pharmaceutically acceptable carrier (instant claim 115, ‘596 claim 21).
Notably, the claims differ in that while the instant claims include specific subtypes of influenza from which the HA stem is derived, a carrier, or more specifically an LNP, or particularly LNPs, in which the mRNAs are formulated, specific lengths of the HA stem polypeptide, wherein the mRNA is self-replicating, or kits or vaccines comprising the mRNAs, ‘596 does not.
However, as discussed in the rejection under 35 U.S.C. §103 above, those limitations, and all of the claims, are rendered obvious by the references Ciaramella, Hoge as evidenced by Anderluzzi, and Bertholet Girardin.
It would have been obvious to modify the reference claims with the teachings of Ciaramella, Hoge as evidenced by Anderluzzi, and Bertholet Girardin to come upon the instant claims. An LNP carrier comprising a PEG-modified lipid, a non-cationic lipid, a sterol, and an ionizable cationic lipid would have been obvious to one of ordinary skill in the art due to LNP carriers for mRNA vaccines are disclosed by Ciaramella and Bertholet Girardin. As described above in the rejection under 35 U.S.C. §103, a lipid nanoparticle constructed of a PEG-modified lipid, a non-cationic lipid, a sterol, and a non-ionisable cationic lipid and containing mRNA encoding an influenza HA stem polypeptide is obvious as all particle components are used in the art for the same purpose, a reasonable expectation of success is had that they will form a functional particle for mRNA delivery since they are part of its prior-art recognized optional ingredients. The amount of each is a result effective variable which will be arrived at by routine experimentation. Ciaramella teaches mRNA vaccines with N1-methylpseudouridine chemical modification, and Hoge discloses kits for the selection, design, and/or utilization of the mRNA vaccines. Ciaramella discloses influenza HA stems within the length of 130 to 400 residues. Bertholet Girardin discloses bicistronic self-replicating bicistronic vectors encoding different Group 1 and Group 2 HAs. One of ordinary skill in the art would have been motivated to make or use influenza vaccines. There would have been a reasonable expectation of success because similar compositions and their use are known in the cited references. Accordingly, instant claims 95-99 and 101-117 were prima facie obvious to one of ordinary skill in the art.
Conclusion
No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEFFREY MARK SIFFORD whose telephone number is (571)272-7289. The examiner can normally be reached 8:30 a.m. - 5:30 p.m. ET with alternating Fridays off.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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