DETAILED ACTION
Applicant’s amendment and remarks filed August 21, 2026 are acknowledged and entered. election without traverse of species position V57 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. The elected species is wildtype at position V57, and H7N9 influenza. However, claim 1 and all dependent claims have been amended to wildtype at all positions V57, Q58, S136 and M140. While the Office generally does not permit a shift to another species mid-prosecution, the examiner will permit it in this instance to further prosecution. Claims 5 and 9-14 are withdrawn from consideration being directed to non-elected species.
Any prior objection or rejection that is not repeated or addressed below is either moot or withdrawn in view of Applicant’s amendment.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 pseudovirus nanoparticle (PVNP) composition comprising an aggregate of fusion protein forming an icosahedral structure of T=1 symmetry (claim 19) and a nanoparticle shell. The PVNP has a diameter of from 20 nm to 21 nm, or about 21 nm (claim 2). The fusion protein is tag-free (claim 18) and comprises:
A modified norovirus (NoV) shell (S) domain protein that is wildtype at all positions V57, Q58, S136 and M140 with reference to SEQ ID NO: 1 (an embodiment of claim 4); a plurality of modified NoV S domain proteins form the interior of the nanoparticle shell; the shell displays 60 exposed C-termini of the S domain in a triangular pattern;
An H7N9 influenza hemagglutinin 1 (HA1) antigen (claim 7); there are 60 HA1 antigens on an exterior surface of the nanoparticle shell, arranged as 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% identity 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 HA1 antigen is of influenza subtype H7N9 comprises SEQ ID NO: 2 (claim 8). SEQ ID NO: 2 is 226-aa, representing H7N9 subtype HA1. 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 having a diameter of 20 nm to 21 nm, or 21 nm, as determined by cryo-electron microscopy, comprising:
Providing a plasmid comprising a nucleic acid sequence encoding a tag-free fusion protein comprising a modified NoV S domain, a linker and an HA1 antigen; the modified NoV S domain protein comprises an R69A mutation (claim 38);
Expressing the tag-free fusion protein in an E. coli or a eukaryotic cell system (yeast, baculovirus/insect, mammalian (claim 30));
Lysing the cells of the cell system expressing the tag-free fusion protein to produce a lysate; and
Precipitating the tag-free fusion protein from the lysate with (NH4)2SO4 at a concentration of between about 0.7 and about 1.2 M.
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 1-4, 7, 8, 15-20, 22-27, 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.
Claim 1 and all dependent claims recite, “a modified norovirus (NoV) S domain protein wherein said NoV S domain protein is wildtype at all positions V57, Q58, S136, and M140”. It is not clear how the S protein is “modified”. Positions V57, Q58, S136, and M140 are wildtype, and thus not modified. There is no indication as to the purpose of the modification. The metes and bounds of a “modified” S protein cannot be determined. Similarly, in claim 29 and its dependent claim 30, the structure and function of a “modified” S protein is not provided, thus the metes and bounds cannot be determined.
Claim 2 recites “said PVNP has a diameter of about 21 nanometers”. Claim 2 is dependent on claim 1. This limitation does not match with the limitation in independent claim 1, wherein the diameter is “from 20 nm to 21 nm”. The “about 21 nanometers” in claim 2 exceeds the scope of the clear upper limit of 21 nm in claim 1.
Claim 38 recites a mutation, R69A. This amino acid position needs 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.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4, 7, 18 and 19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 is directed to an embodiment wherein the S protein is wildtype at one or more positions V57, Q58, or S136, and M140. Claim 4 is dependent on claim 1. The limitation in claim 4 fails to further limit claim 1, which requires that all positions V57, Q58, S136, and M140 are wildtype.
Claims 7, 18 and 19 recite limitations that are already recited in independent claim 1, from which they all depend.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 and 22-27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tan and Jiang (WO 2018/182983 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 (see paragraph [0041]) (claim 1, addressing aspect of modified S). 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). While cysteine mutations V57C, Q58C, S136C and M140C are disclosed, they are not required since the S domain “may comprise” the mutation(s) (see paragraph [0047]) (claims 1 and 4, addressing aspect of wildtype). 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 (claims 1 and 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 20 nm (see paragraph [0078]), which falls within the scope of “from 20 nm to 21 nm” (claim 1) and 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.
Applicant’s arguments filed August 21, 2026 are acknowledged but fail to persuade. Applicant argues that the claims as amended do not teach each and every limitation. However, as outlined above, the claims remain anticipated by Tan.
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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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
