DETAILED ACTION
Applicant’s amendment and remarks filed November 7, 2025 are acknowledged.
Claims 1-4, 7, 10-12, 14, 15, 20, 26, 28, 29 and 32, species SEQ ID NO: 2, pneumovirus, SEQ ID NO: 37, and SEQ ID NO: 11 are under examination. Claims 5, 22, 24 and 25 are withdrawn from consideration being directed to non-elected subject matter.
Any prior objection or rejection that is not repeated or addressed below is either moot or withdrawn in view of Applicant’s amendment.
Claims Summary
Claim 1 is directed to a nanostructure comprising:
A plurality of first assemblies, each first assembly comprising a plurality of identical first polypeptides, wherein the first polypeptides comprise an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2;
SEQ ID NO: 2 (below) is 155 amino acids in length and represents I53_dn5A*; bold and underlined residues are invariant (claim 2), residues in parentheses are optional: (MG)KYDGSKLRIGILHARWNAEIILALVLGALKRLQEFGVKRENIIIETVPGSFELPYGSKLFVEKQKRLGKPLDAIIPIGVLIKGSTMHFEYICDSTTHQLMKLNFELGIPVIFGVLTCLTDEQAEARAGLIEGKMHNHGEDWGAAAVEMATKFN;
A plurality of second assemblies, each second assembly comprising a plurality of identical second polypeptides, wherein the second polypeptides comprise an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1;
SEQ ID NO: 1 (below) is 120 amino acids in length and represents I53_dn5B*; bold and underlined residues are invariant (claim 2), residues in parentheses are optional: (M)EEAELAYLLGELAYKLGEYRIAIRAYRIALKRDPNNAEAWYNLGNAYYKQGRYREAIEYYQKALELDPNNAEAWYNLGNAYYERGEYEEAIEYYRKALRLDPNNADAMQNLLNAKMREE
wherein the plurality of first and second assemblies non-covalently interact to form a nanostructure, and wherein the nanostructure exterior displays multiple copies of one or more pneumovirus F proteins, or antigen fragments thereof.
The pneumovirus F proteins or antigenic fragments thereof have at least 95% sequence identity to SEQ ID NO: 37 (claims 3 and 14), additionally comprising, for example, 67I, among others in claim 4. SEQ ID NO: 37 is 488 amino acids in length and represents DS-Cav1, a prefusion stabilized form of RSV F.
The proteins or fragments are expressed as a fusion protein with the first and/or second polypeptides. Each fusion protein comprises an amino acid linker positions between the first polypeptide and the one or more pneumovirus F proteins or antigenic fragments thereof, and/or between the second polypeptide and the one or more pneumovirus F proteins or antigenic fragments thereof (claim 15). The fusion protein comprises a sequence having at least 95% sequence identity to SEQ ID NO: 11 (632-aa), which represents RSV_F-dn5B_07. The plurality of first assemblies and/or second assemblies each comprise identical fusion proteins (claim 7). The first and/or second assemblies comprise two or more pneumovirus F proteins or antigenic fragments thereof expressed as a fusion protein with the first and/or second polypeptides (claim 10). In another embodiment, only a subset of the first and/or second polypeptides comprise a fusion protein with an F protein or antigenic fragment thereof (claim 11). Each first assembly comprises a homotrimer of the first polypeptide, and/or each second assembly comprises a homopentamer of the second polypeptide (claim 12).
Also claimed is an immunogenic composition comprising the nanostructure and a pharmaceutically acceptable carrier (claim 26), as well as a method for generating an immune response (claim 28) or treating or limiting a pneumovirus infection in a subject by administering an effective amount of the nanostructure (claim 29). Claim 32 is directed to a process for assembling the nanostructures in vitro, comprising mixing two or more nanostructure components in aqueous conditions to drive spontaneous assembly.
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.
Claims 1, 3, 4, 7, 10-12, 14, 15, 20, 26, 28, 29 and 32 remain 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 claims contain 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.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
The claims are directed to nanostructures comprising a plurality of first assemblies of polypeptides that non-covalently interact with a plurality of second assemblies of polypeptides, displaying pneumovirus F proteins or antigenic fragments on the exterior of the nanostructure. The claims encompass a large genus of polypeptides that form the nanostructures, as well as large genus of F proteins and antigenic fragments. Specifically, the polypeptides have at least 95% sequence identity to SEQ ID NO: 1 and 2. The F proteins have at least 95% identity to SEQ ID NO: 37. The fusion proteins comprised of polypeptides and F proteins have at least 95% identity to SEQ ID NO: 11.
The structure provided in the claims SEQ ID NO: 2 is 155 amino acids in length; 95% identity means that 8 amino acids are substituted or deleted. SEQ ID NO: 1 is 120 amino acids in length; 95% identity means that 6 amino acids are substituted or deleted. Regarding the RSV F protein, SEQ ID NO: 37 is 488 amino acids in length; 95% identity means that 25 amino acids are substituted or deleted. Regarding the fusion protein, SEQ ID NO: 11 is 632 amino acids in length; 95% identity means that 32 amino acids are substituted or deleted. The function provided in the claims is the formation of nanostructures expressing F proteins from these polypeptides.
As for the nexus between the structure and the function, the specification discloses that oligomerizing positions are in bold/underlined font in SEQ ID NO: 1 and 2 (see page 9, lines 26-27). Claim 2 indicates that the residues in bold/underlined font are invariant in SEQ ID NO: 1 and 2. All other claims do not require invariant oligomerizing residues in SEQ ID NO: 1 and 2, which means that those claims may not have the oligomerizing residues required to form nanostructures (i.e., noncovalent interactions). While the specification discloses types of substitutions that may be made (see page 9, lines 14-25), there are no sequences having the degree of variability claimed. Similarly, regarding the prefusion conformation of the F protein in SEQ ID NO: 37, if altered by 5%, the specification does not appear to show examples of variants that retain the prefusion conformation, nor a nexus between the structure and conformation. Further, regarding the fusion protein of SEQ ID NO: 11, if modified by 5%, the specification does not appear to show examples of variants that retain the ability to form nanostructures, nor the nexus between the structure and function.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. Amendment of the claims to require that the invariant amino acid residues of SEQ ID NO: 1 and 2 would overcome this rejection.
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.
Claims 1-4, 6, 7, 10-12, 14, 15, 26, 28, 29 and 32 remain rejected under 35 U.S.C. 103 as being unpatentable over King et al. (WO 2018/187325 A1, filed April 3, 2018, cited in the IDS filed 2/14/2024, “King”) in view of Baker et al. (US Patent 10,818,377 B2, filed 11/15/2017, “Baker”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
King discloses self-assembling protein nanostructures displaying on their exterior pneumovirus F proteins, comprising a plurality of first assemblies each comprising a plurality of identical first polypeptides, and a plurality of second assemblies each comprises a plurality of identical second polypeptides, wherein the two assemblies non-covalently interact to form nanostructures (see King, abstract) (claim 1).
One of the F proteins disclosed by King is DS-Cav1-foldon, SEQ ID NO: 60 (residues 26-513), which is identical to Applicant’s SEQ ID NO: 37 (residues 1-488) (see King, page 34), also with mutations, such as A149C, Y458C, among others (see King, page 30) (claims 3, 4 and 14).
The F protein is expressed as a fusion protein with a first polypeptide (see King, page 34, lines 10-11), and the assemblies comprise identical fusion proteins (see King, claim 12) (claims 6 and 7). Two or more F proteins are contemplated (see King, claim 13) (claim 10). Only a subset of the first polypeptides comprise a fusion protein with the F protein (see King, claim 14) (claim 11).
Each first assembly comprises a homotrimer of the first polypeptide (see King, claim 15) (claim 12). Linkers are contemplated, placed between the first polypeptide and the F protein (see King, claim 17) (claim 15). Also disclosed are immunogenic compositions comprising a pharmaceutically acceptable carrier, methods of inducing an immune response, treating or limiting a pneumovirus infection, and assembling nanostructures (see King, claims 34, 36, 37 and 40) (claims 26, 28, 29 and 32).
King does not disclose the instantly claimed sequences of the first and second polypeptides, SEQ ID NO: 1 and 2. However, King suggests the use of any polypeptides that form nanostructures, with no particular sequences required (see King, pages 9-10). Thus, one would have been motivated to use Baker’s self-assembling polypeptides, such as SEQ ID NO: 39 and 40 in King’s construct, with a reasonable expectation of success. Baker’s SEQ ID NO: 39 is 153-aa, 98.6% identical, or 100% identical without the optional residues MG at positions 1 and 2 of Applicant’s SEQ ID NO: 2. Baker’s SEQ ID NO: 40 is 119-aa, 99.2% identical or 100% identical without the optional residue M at position 1 of Applicant’s SEQ ID NO: 1. Baker teaches that the polypeptides of SEQ ID NO: 39 and 40 form protein assemblies such as trimers and pentamers, and certain amino acids are conserved which match those of instant claim 2 (see Baker, claims 1-13, and col. 33, lines 41-46) (claims 1, 2 and 12). Therefore, the claimed invention would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Applicant’s arguments filed November 7, 2025 have been carefully considered. Applicant argues that because King’s construct efficiently forms nanoparticles, one would not have looked to Baker to mix and match the polypeptides that form nanoparticles.
In response, King suggests the use of any polypeptides that form nanostructures, with no particular sequences required (see King, pages 9-10, particularly page 10, lines 11-12). Thus, one would have been motivated to use any suitable self-assembling polypeptides, such as Baker’s SEQ ID NO: 39 and 40, in King’s construct, with a reasonable expectation of success. Baker teaches that the polypeptides of SEQ ID NO: 39 and 40 form protein assemblies such as trimers and pentamers (see Baker, claims 1-13, and col. 33, lines 41-46).
Applicant also argues unexpected results observed with regard to a particular construct. Bringing attention to a comparison between DS-Cav1-I53-50A (“309”, which is related to King’s DS-Cav1-foldon) and Applicant’s construct RSV_F-dn5B-07 (“387”, Applicant’s SEQ ID NO: 11). Referencing Figures 4A and 4B, Applicant’s “387” retains more D25 binding after 1 hour at 50°C than “309”, indicating that the prefusion conformation of the RSV F antigen is more stable in “387” than “309”.
In response, the particular embodiment encompassing RSV_F-dn5B-07 (“387”, Applicant’s SEQ ID NO: 11), claim 20, is no longer rejected, also because the claim now requires at least 95% identity to SEQ ID NO: 11, which is not taught.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/STACY B CHEN/Primary Examiner, Art Unit 1671