DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of species positionV57 and subtype H7N9 in the reply filed on February 16, 2026 is acknowledged. Claims 1-4, 7, 8, 15-20, 22-27, 29, 30 and 38 are under examination. Claims 5 and 9-14 are withdrawn from consideration being directed to non-elected species.
Claims Summary
Claim 1 is directed to a pseudovirus nanoparticle (PVNP) composition comprising an aggregate of fusion protein forming an icosahedral structure (T=1 symmetry (claim 19)) and a nanoparticle shell. The PVNP has a diameter of about 21 nm (claim 2). The fusion protein (tag-free (claim 18)) comprises:
A modified norovirus (NoV) shell (S) domain protein that forms the interior of the nanoparticle shell; the shell displays 60 exposed C-termini of the S domain in a triangular pattern;
A hemagglutinin 1 (HA1) antigen of influenza virus; there are 60 HA1 antigens displayed on the surface of the nanoparticle shell, forming 20 HA1 trimers; and
A peptide linker connecting the C-terminus of the S domain protein to the HA1 antigen
The S protein domain comprises or consists of at least 90%-100% homology to SEQ ID NO: 1 (claim 3). SEQ ID NO: 1 is 199-aa and represents an S protein domain from NoV, genogroup II, genotype 4. The NoV S domain protein is wildtype at position V57 (claim 4) or comprises an R69A mutation (claim 38).
The HA1 antigen is of influenza subtype H7N9 (claim 7) and has at least 90% sequence homology with SEQ ID NO: 2 (claim 8). SEQ ID NO: 2 is 226-aa, representing H7N9 subtype. The HA1 antigen comprises or consists of a region covering the receptor binding site (RBS) (claim 15). The HA1 antigen is glycosylated (claim 16).
The linker comprises or consists of a sequence selected from HHHH, GGGG or GSGS (claim 17).
The PVNP induces substantial immunity to influenza virus infection or at least one symptom thereof when administered to a subject (claim 20). “Substantial immunity” is defined in paragraph [0034] of the published application (US 20240226267) as immunity that prevents influenza infection, improves influenza infection, or reduces at least one symptom related to influenza virus infection. Also claimed is a method of eliciting an immune response in a subject in need thereof against an influenza virus comprising administering the PVNP composition in an amount effective to produce an antigen-specific immune response (claim 22). The composition is administered as a dose (claim 23) comprising from about 1 to about 150 µg of PVNP (claim 27). Administration is via a route selected from intradermal, intramuscular and intranasal (claim 24). The composition comprises a pharmaceutically acceptable carrier (claim 25), or one or more of an adjuvant and a preservative (claim 26).
Also claimed is a method of making a PVNP, comprising:
Providing a plasmid comprising gene sequences corresponding to a modified NoV S domain, a linker and an HA1 antigen, wherein the sequence is tag-free;
Expressing a gene product of said sequences in an E. coli or a eukaryotic cell system (yeast, baculovirus/insect, mammalian (claim 30));
Lysing the cells of the cell system expressing a S-HA1 antigen; and
Precipitating the gene product from the cells with (NH4)2SO4 at a concentration of between about 0.7 and about 1.2 M
Claim Objections
Claims 1-4, 7, 8, 15-20, 22-27 and 38 are objected to because of the following informalities:
Claim 1, part b) recites “a hemagglutinin I (HA1) antigen of influenza hemagglutinin I (HA1) of influenza virus”. “I” should be “1”. The phrase is redundant in its two recitations of HA1. Claims 2-4, 7, 8, 15-20, 22-27 and 38 are included in this objection because they depend from claim 1.
Claim 22 recites “A method of eliciting an immune response in a subject against an influenza virus in an individual in need thereof against an influenza virus”. Since the subject is the individual, consistent terminology should be used. Further, the phrase is redundant in its two recitations of “against an influenza virus”. Claims 23-27 are included in this objection because they depend from claim 22. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 4, 8, 29, 30 and 38 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3 and 8 refer to “sequence homology” to SEQ ID NO: 1 and 2, respectively. It is not clear what sequences would qualify as homologous. The specification does not provide a definition of “homology”. Paragraph [0021] of the published application (US 20240226267) refers to degrees of homology, but no definition is given. The metes and bounds of the homologous sequences cannot be determined. Suggested language is “sequence identity”.
Claim 4 recites an amino acid position, V57. Claim 38 recites a mutation, R69A. These amino acid positions need to be referenced by a sequence identifier, otherwise the location will vary depending on the content (i.e., the start) of any given S protein.
Claim 29, part a, recites “gene sequences corresponding to a modified NoV S domain, a linker, and an HA1 antigen”. Sequences that “correspond” are not set forth in the specification such that the metes and bounds of such sequences can be determined. Suggested language is “gene sequences encoding a modified NoV S domain” etc.
Claim 29 recites “wherein said sequence is tag-free”, however, claim 29 recites “sequences”, thus it is not clear which sequence is tag-free. Claim 30 is included in this rejection because it depends from claim 29.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 7, 8, 15, 17-20, 22-27 and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tan and Jiang (WO 2018/0182983 A1, “Tan”, cited in the IDS filed 6/30/2025). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Tan discloses norovirus particle based compositions for antigen presentation, comprising a polyvalent icosahedral (T=1) nanoparticle comprising recombinant fusion proteins comprising NoV shell (S) domain protein, an antigen protein domain, and a linker protein domain connecting the S domain protein to the antigen protein domain (see abstract and paragraphs [0091] and [00109]) (claims 1 and 19). The S domain is modified by, for example, an R69A mutation and a cysteine mutation(s) (see paragraph [0041]) (claim 38). The modified S domain forms the interior shell of the nanoparticle and provides 60 exposed S domain C-termini for antigen presentation (see paragraph [0041]) (claim 1). The cysteine mutations include, for example, V57C, Q58C, S136C, M140C, or a combination thereof (see paragraph [0047]) (claim 4). Tan’s S protein sequence is, for example, SEQ ID NO: 27, which is 221-aa and exactly matches aa 1-199 of Applicant’s SEQ ID NO: 1 (claim 3). Although Tan does not explicitly state that the nanoparticle shell displays the 60 exposed C-termini of the S domain in a triangular pattern, it is an inherent property of the structure, since the sequence is the same as that claimed.
Addressing the peptide linker, Tan discloses a linker comprising, for example, GGGG (see paragraph [0085]) (claim 17). Addressing the HA1 antigen, Tan discloses influenza HA1 receptor binding domain as an antigen in the construct, for example, HA1 from H7 (see paragraph [0050]) (claim 15). Tan’s SEQ ID NO: 47 is an exact match for Applicant’s SEQ ID NO: 2 (claim 8), which means that SEQ ID NO: 47 represents an HA1 from H7N9 (claim 7). Although Tan does not appreciate that the presentation of the 60 HA1 from the nanoparticle results in the formation of 20 HA1 trimers, it is an inherent outcome of expressing the same sequence from the same construct. Paragraph [0082] of the published application states, “Remarkably, the exposed HA1 antigens are arranged into trimers”, which indicates that the formation of trimers is a natural outcome (claim 1). The size of the particles is about 28 nm (see paragraph [0091]), which is reasonably considered “about 21 nm” (claim 2). Tag-free fusion proteins are contemplated (se paragraph [00106]) (claim 18).
Tan discloses methods of eliciting an immune response against influenza virus comprising administering the particles to a subject in need thereof to prevent or ameliorate symptoms of disease, wherein the composition is administered as a dose and comprises a pharmaceutically acceptable carrier, or other immunoregulatory agent (see paragraph [0056]) (claims 20, 22, 23 and 25). Administration is via the intramuscular route, and the composition comprises a dose of 10 µg of particles with an adjuvant or preservative, among other components (see paragraphs [0052], [0054] and [0068]) (claims 24, 26 and 27). Therefore, the claims are anticipated by the prior art.
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.
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.
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 16, 29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Tan and Jiang (WO 2018/0182983 A1, “Tan”, cited in the IDS filed 6/30/2025) as applied to claim 1 above, and further in view of Rasochova et al. (WO 2007/011904 A2, “Rasochova”).
The teachings of Tan are outlined above. Tan discloses methods of making the particles via plasmids and expression in E. coli, wherein the particles produced tag-free and precipitated by ammonium sulfate (see paragraph [00106]). However, Tan does not disclose HA1 that is glycosylated, expression in a mammalian cell system, lysing of cells expressing the HA1 antigen, nor the particular range of concentration of ammonium sulfate between about 0.7 M and about 1.2 M.
Rasochova discloses methods of producing influenza antigens, such as HA, in expression systems, including E. coli, yeast and mammalian expression systems (page 6, third full paragraph, and page 30, third full paragraph) (claims 29-30). Lysis of cells is followed by precipitation with, for example, ammonium sulfate (see pages 31-33) (claim 29). Rasochova discloses the use of ammonium sulfate at a concentration between 20-30% (see page 33, lines 8-10). Although a molarity of about 0.7 to about 1.2 M is not explicitly disclosed, it would have been obvious to have modified or optimized this concentration to fit the precipitation needs of the particular protein solution, as a result-effective variable, i.e., maximum precipitation and protein yield, with a reasonable expectation of success (claim 29). Rasochova discloses the ammonium sulfate concentration as “typical”, thus leaving room for modifications to be made. Addressing the limitation in claim 16, glycosylation is disclosed as a modification to increase antigenicity, increase recombinant expression in a host cell, improve efficiency, etc. (see Rasochova page 7, second full paragraph). Given these advantages, one would have been motivated to glycosylate the HA1 protein of Tan with a reasonable expectation of success. Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 15, 20, 22, 23 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 8, 11 and 12-18 of U.S. Patent No. 11,833,198 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. The patented claims are directed to a polyvalent icosahedral composition for antigen presentation comprising an S particle of NoV (human calicivirus) comprising a fusion protein comprising an S protein domain modified by the mutation R69A, or cysteine substitutions at 57C/140C, 57C/58C/136C, or 57C/58C/136C/140C. The S protein domain is linked by a linker protein domain to an antigen protein domain, such as influenza HA1 receptor-binding domain (patented claim 11). Also claimed is a method of making by recombinant expression in E. coli (patented claims 13 and 14), and a container comprising a dose (patented claim 16).
The patented claims differ from the instant claims. One difference is that the patented claims are directed to species of the instantly claimed genus, specifically, the R69A mutation, the particular cysteine mutations, and the norovirus human calicivirus. In these respects, the species anticipates the genus.
The patented claims also differ from the instant claims in that the instant claims require that the HA1 antigens form 20 trimers. Although instant claim 11 is directed to an antigen such as influenza HA1 receptor-binding domain, it does not state that the HA1 antigens for 20 trimers. However, it appears to be an inherent outcome of expressing the same antigen from the same construct. Paragraph [0082] of the published application states, “Remarkably, the exposed HA1 antigens are arranged into trimers”, which indicates that the formation of trimers is a natural outcome.
Claims 2, 3, 7, 8, 17-19 and 24-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 8, 11 and 12-18 of U.S. Patent No. 11,833,198 B2 as applied to claim 1, and further in view of Tan and Jiang (WO 2018/0182983 A1, “Tan”, cited in the IDS filed 6/30/2025). Although the claims at issue are not identical, they are not patentably distinct from each other.
The patented claims are summarized above but do not include the limitations of instant claims 2, 3, 7,8, 17-19 and 24-27. However, it would have been obvious to have claimed these embodiments in view of the teachings of Tan. Tan discloses norovirus particle based compositions for antigen presentation, comprising a polyvalent icosahedral (T=1) nanoparticle comprising recombinant fusion proteins comprising NoV shell (S) domain protein, an antigen protein domain, and a linker protein domain connecting the S domain protein to the antigen protein domain (see abstract and paragraphs [0091] and [00109]) (addressing instant claim 19). Tan’s S protein sequence is, for example, SEQ ID NO: 27, which is 221-aa and exactly matches aa 1-199 of Applicant’s SEQ ID NO: 1 (addressing instant claim 3).
Addressing the peptide linker, Tan discloses a linker comprising, for example, GGGG (see paragraph [0085]) (addressing instant claim 17). Addressing the HA1 antigen, Tan discloses influenza HA1 receptor binding domain as an antigen in the construct, for example, HA1 from H7 (see paragraph [0050]). Tan’s SEQ ID NO: 47 is an exact match for Applicant’s SEQ ID NO: 2 (addressing instant claim 8), which means that SEQ ID NO: 47 represents an HA1 from H7N9 (addressing instant claim 7). The size of the particles is about 28 nm (see paragraph [0091]), which is reasonably considered “about 21 nm” (addressing instant claim 2). Tag-free fusion proteins are contemplated (se paragraph [00106]) (addressing instant claim 18).
Tan discloses methods of eliciting an immune response against influenza virus comprising administering the particles to a subject in need thereof to prevent or ameliorate symptoms of disease, wherein the composition comprises a pharmaceutically acceptable carrier (see paragraph [0056]) (addressing instant claim 25). Administration is via the intramuscular route, and the composition comprises a dose of 10 µg of particles with an adjuvant or preservative, among other components (see paragraphs [0052], [0054] and [0068]) (addressing instant claims 24, 26 and 27). Given the similar constructs, it would have been obvious to have claimed the embodiments of Tan with a reasonable expectation of success.
Claims 16, 29 and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 8, 11 and 12-18 of U.S. Patent No. 11,833,198 B2 as applied to claim 1, and further in view of Rasochova et al. (WO 2007/011904 A2, “Rasochova”). Although the claims at issue are not identical, they are not patentably distinct from each other.
The patented claims are summarized above but do not include the limitations of instant claims 16, 29 and 30. Patented claims 13 and 14 are directed to methods of making the particles in E. coli, but do not recite embodiments of glycosylation of HA1, expression in a mammalian cell system with a plasmid, lysing of cells expressing the HA1 antigen, nor the use or the particular range of concentration of ammonium sulfate between about 0.7 M and about 1.2 M for precipitation.
Rasochova discloses methods of producing influenza antigens, such as HA, in expression systems, including plasmids, E. coli, yeast and mammalian expression systems (page 6, third full paragraph, page 30, third full paragraph, and page 59, first paragraph) (addressing instant claims 29-30). Lysis of cells is followed by precipitation with, for example, ammonium sulfate (see pages 31-33) (addressing instant claim 29). Rasochova discloses the use of ammonium sulfate at a concentration between 20-30% (see page 33, lines 8-10). Although a molarity of about 0.7 to about 1.2 M is not explicitly disclosed, it would have been obvious to have modified or optimized this concentration to fit the precipitation needs of the particular protein solution, as a result-effective variable, i.e., maximum precipitation and protein yield, with a reasonable expectation of success (addressing instant claim 29). Rasochova discloses the ammonium sulfate concentration as “typical”, thus leaving room for modifications to be made. Addressing the limitation in instant claim 16, glycosylation is disclosed as a modification to increase antigenicity, increase recombinant expression in a host cell, improve efficiency, etc. (see Rasochova page 7, second full paragraph). Given these advantages, one would have been motivated to claim a glycosylated HA1 protein of with a reasonable expectation of success.
Conclusion
No claim is allowed.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
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