DETAILED ACTION
Disposition of Claims
Claims 8-10, 20, 27, 35-36, and 41-47 were pending. Claims 1-7, 11-19, 21-26, 28-34, and 37-44 are cancelled. Amendments to claims 10 and 36 are acknowledged and entered. Claims 8-10, 20, 27, 35-36, and 45-47 will be examined on their merits.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240165218A1, Published 05/23/2024. Amendments to the specification presented on 01/14/2025 and 08/29/2025 are acknowledged and entered.
Optional Authorization to Initiate Electronic Communications
The authorization provided by Applicant’s representative on 08/29/2025 to correspond with the Examiner via electronic mail (e-mail) is acknowledged and entered.
Response to Arguments
Applicant's arguments filed 12/10/2025 regarding the previous Office action dated 09/17/2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Terminal Disclaimer
The terminal disclaimer filed on 08/29/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Pat. No. 11,771,755 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/25/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
(New objection.) Claim 20 is objected to because of the following informalities: the indefinite article “a” before “nanostructure” should be the definite article “the”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(New rejection – necessitated by amendment.) Claim 36 is 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 36 is drawn to a method of in vitro assembling a self-assembling icosahedral protein nanostructure, comprising:
20 trimeric assemblies having 3-fold symmetry, each trimeric assembly comprising 3 trimer proteins, each trimer protein comprising a polypeptide, in N- to C-terminal order, an antigenic protein, a polypeptide linker, and a trimer subunit comprising a polypeptide comprising an amino acid sequence that is at least 9500 identical to the amino acid sequence selected from SEQ ID NO: 7or 29-31: and
12 pentameric assemblies having 5-fold symmetry, each pentameric assembly comprising 5 pentamer subunits, wherein each pentamer subunit comprises a polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence selected from SEO ID NO: 8 or 32-34;
wherein the trimeric assemblies and the pentameric assemblies form an icosahedron;
wherein the antigenic protein is Epstein-Barr virus (EBV) glycoprotein 350 (gp350); and
wherein the antigenic protein, the polypeptide linker, and the trimer subunit are encoded by a single open reading frame that encodes a fusion protein of the antigenic protein, the polypeptide linker, and the trimer subunit and encodes a self-cleaving peptide,
the method comprising:
expressing the trimer proteins in a first recombinant expression system,
expressing the pentameric subunits in a second recombinant expression system,
purifying the trimer proteins,
purifying the pentamer subunits, and
mixing the trimer proteins and pentamer subunits;
thereby generating the nanostructure.
The wording of claim 36 makes it confusing as to whether the limitations after “comprising” in line 2 are intended to be steps to the method or if said limitations are the elements of the self-assembling icosahedral protein nanostructure. As the latter interpretation appears to be correct, it is suggested that the claim be worded in line 2 to recite “…nanostructure, wherein said nanostructure is comprising:…” Additionally, it is suggested at line 17 that the line recite “…wherein the method comprises the steps of:” and then delineates each step with a bullet or a numerical letter followed by a colon to clarify that those are the specific method steps.
For at least these reasons, claim 36 is rejected on the grounds of being indefinite.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 10 is drawn to a self-assembling icosahedral protein nanostructure, comprising:
20 trimeric assemblies having 3-fold symmetry, each trimeric assembly comprising 3 trimer proteins, each trimer protein comprising a polypeptide, in N- to C-terminal order, an antigenic protein, a polypeptide linker, and a trimer subunit comprising a polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence selected from SEQ ID NO: 7 or 29-31; and
12 pentameric assemblies having 5-fold symmetry, each pentameric assembly comprising 5 pentamer subunits, wherein each pentamer subunit comprises a polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence selected from SEQ ID NO: 8 or 32-34;
wherein the trimeric assemblies and the pentameric assemblies form an icosahedron; wherein the antigenic protein is Epstein-Barr virus (EBV) glycoprotein 350 (gp350); and
wherein the polypeptide linker comprises a polypeptide sequence selected from GSGGSGSGSGGSGSG (SEQ ID NO:114), GGSGGSGS (SEQ ID NO:115), and GSGGSGSG (SEQ ID NO:116.
Further limitations on the nanostructure of claim 10 are wherein the antigenic protein comprises the amino acid sequence of SEQ ID NO: 59 (claim 8), wherein the antigenic protein comprises an amino acid sequence that is at least 75% identical to the amino acid sequence of SEQ ID NO: 59 (claim 9); a vaccine comprising a nanostructure of claim 10, wherein the vaccine is capable of eliciting a neutralizing antibody response to EBV (claim 20); a pharmaceutical composition comprising the vaccine of claim 20 (claim 35); wherein each trimer subunit comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7 (claim 45); wherein each pentamer subunit comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34 (claim 46); and wherein each trimer subunit comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and wherein each pentamer subunit comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34 (claim 47).
Claim 27 is drawn to a method of generating immunity to EBV in a subject, the method comprising administering the vaccine of claim 20.
Claim 36 is drawn to a method of in vitro assembling a self-assembling icosahedral protein nanostructure, wherein said nanostructure is comprising:
20 trimeric assemblies having 3-fold symmetry, each trimeric assembly comprising 3 trimer proteins, each trimer protein comprising a polypeptide, in N- to C-terminal order, an antigenic protein, a polypeptide linker, and a trimer subunit comprising a polypeptide comprising an amino acid sequence that is at least 9500 identical to the amino acid sequence selected from SEQ ID NO: 7or 29-31: and
12 pentameric assemblies having 5-fold symmetry, each pentameric assembly comprising 5 pentamer subunits, wherein each pentamer subunit comprises a polypeptide comprising an amino acid sequence that is at least 95% identical to the amino acid sequence selected from SEO ID NO: 8 or 32-34;
wherein the trimeric assemblies and the pentameric assemblies form an icosahedron;
wherein the antigenic protein is Epstein-Barr virus (EBV) glycoprotein 350 (gp350); and
wherein the antigenic protein, the polypeptide linker, and the trimer subunit are encoded by a single open reading frame that encodes a fusion protein of the antigenic protein, the polypeptide linker, and the trimer subunit and encodes a self-cleaving peptide,
wherein the method comprises the steps of:
expressing the trimer proteins in a first recombinant expression system,
expressing the pentameric subunits in a second recombinant expression system,
purifying the trimer proteins,
purifying the pentamer subunits, and
mixing the trimer proteins and pentamer subunits;
thereby generating the nanostructure.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, 41-42, and 45 under 35 U.S.C. 103 as being unpatentable over Lajoie et. al. (WO2016138525A1, Pub. 09/01/2016, Priority 02/27/2015; CITED ART OF RECORD; hereafter “Lajoie”) in view of Kanekiyo et. al. (US20160303224A1, Pub. 10/20/2016; hereafter “Kanekiyo”) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 45-47 under 35 U.S.C. 103 as being unpatentable over Lajoie and Kanekiyo as applied to claims 8-10, 20, 27, 35-36, 41-42, and 45 above, and further in view of Baker et. al. (US20160122392A1, Pub. 05/05/2016; hereafter “Baker”) is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Lajoie et. al. (WO2016138525A1, Pub. 09/01/2016, Priority 02/27/2015; CITED ART OF RECORD; hereafter “Lajoie”) in view of Kanekiyo et. al. (US20160303224A1, Pub. 10/20/2016; CITED ART OF RECORD; hereafter “Kanekiyo”) and King et. al. (US20200392187A1; Priority 04/04/2017; hereafter “King”.)
The applied reference (King) has at least one common inventor (King, Baker) and at least one common assignee (University of Washington) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The Prior Art
Lajoie teaches multimeric assemblies including multiple oligomeric substructures, such as nanoparticles, wherein the nanoparticles self-assemble around at least one axis of rotational symmetry, where each protein includes one or more polypeptide-polypeptide interface ("O interface"); and one or more polypeptide domain(s) that allows the nanoparticle to be released from or enter into a cell ("L domain"); and wherein the nanoparticle includes one or more subunits comprising one or more polypeptide domain(s) that is capable of interacting with a lipid bilayer ("M domain")(entire document; see abstract; pp. 68-9, ¶ bridging pages.) Lajoie teaches the O-interface containing the first protein and the second proteins comprises the protein pairs of SEQ ID NOs: 10-19 (e.g. SEQ ID NO:10 and 11 are pair (a), SEQ ID NO: 12 and 13 are pair (b), etc.) or SEQ ID NOs: 270-279, which comprise pairs of the nanoparticle-forming peptides (e.g. SEQ ID NO: 270 is I53-34A and is paired with SEQ ID NO: 271 which is I53-34B, wherein SEQ ID NO: 270 is 100% identical to instant SEQ ID NO:1 and SEQ ID NO: 271 is 100% identical to instant SEQ ID NO:2 (pp. 28-29, ¶8 to ¶2.) SEQ ID NO:7 of the instant invention is I53-50A, while SEQ ID NO:34 is I53-50B.4PosT1; Lajoie teaches I53-50A (SEQ ID NO:276, which is 100% identical to instant SEQ ID NO: 7; instant claim 45) and I53-50B (SEQ ID NO: 277; which is 94% identical to instant SEQ ID NO: 34) as a pair (p. 29, line 7), wherein instant SEQ ID NO:7 and reference SEQ ID NO:276 are 100% identical (see NCBI BLAST sequence analysis in parent) and instant SEQ ID NO: 34 and reference SEQ ID NO: 277 are 94.9% identical (see NCBI BLAST sequence analysis in parent). Further, instant SEQ ID NO: 31 aligns to reference SEQ ID NO: 276 of Lajoie with 96.9% identity; instant SEQ ID NO: 32 aligns with 97.8% identity to reference SEQ ID NO: 277 of Lajoie.
Lajoie teaches that transmembrane or membrane-anchored proteins may be present within the nanoparticle (reference claim 21) and teaches SEQ ID NO:315, which is a sequence for influenza hemagglutinin, an antigenic surface glycoprotein of influenza virus, and which Lajoie teaches is useful as acting as the transmembrane or membrane-anchored protein embedded in the lipid bilayer (reference claim 23). Lajoie teaches the transmembrane proteins may be from other viruses, such as Vesicular stomatitis virus (VSV), Moloney Murine leukemia virus (MMLV), amphitropic murine leukemia virus, Sindbis virus (E3-E2-6K-E1 Env), Ebola virus, HIV (gp160), respiratory syncytial virus (RSV; F protein), SARS CoV (spike protein), or influenza virus, and provides at least one known sequence for each virus (pp. 58-61).
Lajoie teaches the proteins generating the nanoparticle may comprise fusion proteins to polypeptide domains or sequences to carry desired cargo (pp. 39-40, ¶2 to ¶2), wherein the fusion may occur at the N- or C- terminus depending on the positioning of the M or L domain, and the fusion occurs through a flexible linker (p. 69, ¶2-4.) Lajoie teaches the linker peptides may be ser/gly flexible linkers, such as GSGS (¶bridging pp. 46-47 to ¶2, p. 47; p. 70, ¶3.)
Lajoie teaches the presence of viral membrane proteins on the surface of the nanoparticle can facilitate entry into a cell and can also be immunogenic for the purpose of eliciting a therapeutic vaccine immune response (p. 79, ¶2; reference claim 7; p. 10, ¶5; p. 57, ¶2.) Lajoie therefore teaches nanostructures which comprise, at least, SEQ ID NOs: 1-2 with an influenza HA polypeptide fused to the C-terminal portion of one of said proteins (instant claims 20, 27, 35.) Lajoie teaches there can be one or more antigens utilized in the nanostructure (p. 2, ¶1; p. 3, ¶1; pp. 57-8, ¶ bridging pages). Lajoie teaches that the two heterologous proteins may be fused to one another (BlaM-Vpr fusion; p. 78.)
Lajoie teaches methods of making the nanostructures, including recombinant expression systems (p. 10, ¶6) that include recombinant expression vectors which comprise the nucleic acid encoding the polypeptides (pp. 62-63, ¶ bridging pages; pp. 64-5, ¶ bridging pages), wherein said pentameric and trimeric assemblies can be expressed from distinct expression vectors (p. 65; ¶3), and expressing said vectors in host cells (p. 65, ¶2). The polypeptides expressed in host cells can be recovered and purified (p. 66, ¶2) or the nanostructures may be expressed within the cells and then recovered (p. 18, ¶3; p. 66, ¶3-4).
While Lajoie teaches a few viral envelope sequences, and teaches that viral envelope/surface/transmembrane proteins may be present in the nanostructure. Lajoie does not appear to teach the insertion of sequences from Epstein-Barr virus (EBV), such as any gp350 sequences or a sequence with at least 75% identity to instant SEQ ID NOs: 59. While Lajoie teaches that flexible ser/gly linkers may be used to join the different domains of the nanoparticle, Lajoie fails to teach a ser/gly linker with any of the specific sequences of instant SEQ ID NOs: 114-116. Additionally, Lajoie does not teach the use of self-cleaving peptides in these sequences. However, the delivery of EBV gp350 sequences via nanoparticles for the purpose of vaccine platforms were known in the art, as evidenced by the teachings of Kanekiyo. Kanekiyo further teaches the use of self-cleaving sites, such as picornavirus 2A sites, and teaches the use of flexible ser/gly linkers. Finally, ser/gly linkers were well-known in the art, as were various sequences for said linkers, as evidenced by the teachings of King.
Kanekiyo teaches vaccine compositions that elicit neutralizing antibodies to Epstein-Barr virus (EBV). Some vaccines comprise nanoparticles that display envelope proteins from EBV on their surface. Kanekiyo teaches nanoparticles comprise fusion proteins comprising a monomeric subunit of a self-assembly protein joined to at least a portion of an EBV envelope protein, wherein the fusion proteins self-assemble to form the envelope protein-displaying nanoparticles. Such vaccines can be used to vaccinate an individual against infection by different types of Epstein-Barr viruses as well as Epstein-Barr viruses that are antigenically divergent from the virus from which the EBV envelope protein was obtained. Kanekiyo teaches nucleic acids which encode said EBV-fusion proteins (entire document; see abstract.) Kanekiyo teaches the compositions may be formulated and administered using known pharmaceutical techniques in the art (¶0149]). Said EBV proteins which are fused to the self-assembly proteins may be the outer glycoprotein gp350 or an immunogenic portion thereof (¶[006]). Kanekiyo teaches SEQ ID NO: 32 (¶[0006]; Table 2), which is 100% identical to instant SEQ ID NO: 59 (see alignment in previous Office action; SEQ ID NO: 32 is Qy while SEQ ID NO: 59 is Db.) Kanekiyo teaches the fusion proteins may comprise linkers (¶[0020]), such as ser-gly linkers (¶0029-0030][0079][0099][0110][0117][0162-0162]; SEQ ID NOs:145-146; Table 2). Kanekiyo teaches the nanoparticles displaying gp350 can elicit neutralizing antibodies, especially in the presence of further adjuvants (¶[0204]). Kanekiyo teaches the EBV protein can be expressed as a single polycistronic protein with intervening self-cleaving peptide sequences between protein units (¶[0049]; Table 2; SEQ ID NOs: 137-138, 141-144), as Kanekiyo teaches in certain embodiments it is useful to have the antigenic protein directly joined to the nanoparticle structural unit, but also useful to employ linkers, spacers, or cleavage sequences in order to maintain stoichiometry (or molecular ratio) of the final proteins, maintain proper orientation of domains in the final fusion protein, to facilitate transport of the final protein within or out of a cell, or to allow cleavage of the final protein (¶[0117]). These cleavage sequences may be self-cleavage sites, such as picornavirus protease cleavage sites (¶[0117-0118]).
King teaches self-assembling protein nanoparticles, wherein said nanoparticles are a combination of assemblies, wherein at least one assembly presents a surface antigen from a viral protein (entire document; see abstract.) King teaches icosahedral nanostructures (¶[0040]) which form from the combination of I53-50A or variants thereof (¶[0025]; reference claim 9) and I53-50B (Table 1; reference claim 6.) King teaches SEQ ID NO: 88, which is 99.5% identical to instant SEQ ID NO: 7 (See ABSS sequence alignment file; us-18-359-154-7.rai) and teaches SEQ ID NO: 34, which is 100% identical to instant SEQ ID NO: 34 (See ABSS sequence alignment file; us-18-359-154-34.rai; instant claims 45-47.)
King teaches the use of amino acid linker sequences, such as gly/ser linkers, that are within the protein comprising the antigen and trimerization domain (¶[0017][0025]), wherein the gly/ser linker may be of SEQ ID NO: 57, which is 100% identical to instant SEQ ID NO: 116 (¶[0126]). King teaches the in vitro formation of the icosahedral nanoparticles, wherein the trimeric assemblies and pentameric assemblies were expressed separately, purified, and then mixed together to allow for formation of the nanoparticles, after which the desired pentamers were further isolated and characterized (¶[0168-0172]).
Given the teachings of Lajoie, which teach the self-assembling proteins needed to form the I53-based nanoparticles, and given that Lajoie teaches these protein monomers can express viral surface protein antigens as fusion proteins, especially through the use of flexible ser/gly linkers, one of skill in the art would be apprised as to this nanoparticle delivery system for antigens, especially viral envelope protein antigens, and would be motivated to determine if substitution of one known viral antigen with another would produce similar antigenic results. This would be further supported by the teachings of King, which also teach the expression of viral surface antigens on I53-based icosahedral nanoparticles, and the use of flexible gly/ser linkers to join portions of the nanoparticle subunits to their heterologous cargo. Given the teachings of Kanekiyo, one of skill in the art would be apprised to antigenic EBV proteins, such as gp350, and the usefulness of expressing multiple gp350 proteins on the surface of a nanoparticle in order to get better B cell activation. Kanekiyo also teaches the use of ser/gly linkers, and the use of self-cleaving peptides to aid in the stoichiometric expression, stability, and release of cargo. Kanekiyo, Lajoie, and King also teach in vitro methods of assembling the nanoparticles, especially through expression of the pentameric and trimeric portions separately, isolation/purification of said components, mixing of said components, and isolation of the formed icosahedral nanoparticles. Through the combined teachings of Lajoie, King, and Kanekiyo, arriving at the limitations of instant claims 10 and 36 would therefore be obvious to a skilled artisan.
As Lajoie teaches the use of virus envelope proteins in the I53 nanostructures, these envelope protein sequences inherently comprise neutralizing antibody target epitopes as required by instant claim 20 (for instance, the influenza HA of Lajoie shares 100% identity to known influenza A HA over the full-length of said known HAs (see attached NCBI BLAST of SEQ ID NO: 315.)) Further, Kanekiyo teaches that the EBV gp350 displayed on the nanoparticles comprise neutralizing antibody epitopes (¶[0204]). Therefore, arriving at the limitations of instant claim 20 would be obvious to a skilled artisan in light of Lajoie, King, and Kanekiyo.
Lajoie teaches the use of the nanostructures in vaccines (p. 10, ¶5; p. 57, ¶2), wherein said vaccines would inherently be pharmaceutically-acceptable compositions as required by instant claims 20 and 35 and useful in therapeutic vaccination methods to induce immunity as required by instant claim 27. King teaches the nanoparticles would be within immunogenic compositions comprising a pharmaceutically acceptable carrier and adjuvant (reference claims 34-35). Further, Kanekiyo renders these pharmaceutical compositions obvious, as Kanekiyo teaches the use of the gp350-expressing nanoparticles in vaccine compositions, the delivery of said pharmaceuticals to elicit a neutralizing antibody response, and the methods and compositions available in the art for doing so. Therefore, arriving at the limitations of instant claims 20, 27, and 35 would be obvious to a skilled artisan, given the teachings of Lajoie, King and Kanekiyo.
As sequences for the EBV gp350 viral antigens listed in instant claim 10 were well-known in the prior art, as evidenced by the teachings of Kanekiyo, and it was well-known in the art to utilize these viral surface antigens for immunogenic purposes, it would be obvious to arrive at the limitations of instant claims 8-9, given the combined teachings of Lajoie, King and Kanekiyo. As Lajoie and King teach the use of viral surface proteins, such as HIV Env and respiratory syncytial virus (RSV) fusion (F) protein, it would be obvious to utilize known sequences in the art from Kanekiyo to amend the teachings of Lajoie and King to arrive at the limitations of instant claims 8-9.
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Lajoie in order to utilize viral transmembrane surface proteins on the nanostructure. One would have been motivated to do so, given the suggestion by Lajoie and King that the nanostructures could utilize such proteins as viral envelope proteins, such as HIV Env or RSV F. There would have been a reasonable expectation of success, given the knowledge that sequences for known viral antigenic surface proteins were known in the art, as taught by Kanekiyo, and that EBV gp350 fusion proteins to other self-assembling proteins that generate nanoparticles are an effective way of generating neutralizing antibodies. One would have been motivated to utilize the superior nanoparticle system of Lajoie and King to improve upon the teachings of Kanekiyo, which required the use of adjuvants in their gp350-displaying nanoparticle system to be the most effective. One of skill in the art would be apprised of the use of linkers and self-cleaving peptides to aid in stability and expression of the nanoparticles, as taught by Lajoie, King, and Kanekiyo. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant’s arguments, see “Remarks”, filed 12/102025, with respect to the rejections of the claims under 35 USC 103 have been fully considered and are persuasive, and all rejections have been withdrawn. However, upon further consideration, new grounds of rejection using Lajoie is made in view of Kanekiyo and King, and arguments regarding Lajoie and Kanekiyo will be addressed as applicable herein, as these teachings were utilized in previous rejections.
Applicant argues that limitations from canceled claims 43 and 44 were not previously rejected under the obviousness rejections, and have been incorporated into the amended independent claims. However, upon further search and consideration, these limitations, especially in light of the newly amended claims, were known in the prior art and would have been obvious to a skilled artisan for the reasons set forth supra.
The teachings of Baker were not utilized in this current rejection.
For at least these reasons, the claims remain rejected on the grounds of being obvious over the teachings of Lajoie, Kanekiyo, and King for at least the reasons set forth supra.
Double Patenting
The text regarding nonstatutory double patenting was presented in a previous Office action.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Pat. No. 11,192,926 in view of Lajoie, Kanekiyo, and Baker (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Pat. No. 11,732,011 in view of Lajoie, Kanekiyo, and Baker (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of U.S. Pat. No. 12,275,757 in view of Lajoie, Kanekiyo, and Baker (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Pat. No. 9,630,994 in view of Lajoie and Kanekiyo (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Pat. No. 10,351,603 in view of Lajoie and Kanekiyo (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Pat. No. 11,485,759 in view of Lajoie and Kanekiyo (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 8, 11-14, 17-19, 21-22, 24, 26, 32-34, 42, 45, 48, 57, 63, 77-78, 82-85, 88, 90, and 95 of Copending App. No. 17/423,565 in view of Lajoie, Baker, and Kanekiyo (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 10-12, 14-15, 20, 22, 24-26, 28-29, and 32 of Copending App. No. 17/639,442 in view of Lajoie, Baker, and Kanekiyo (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of Copending App. No. 18/459,654 in view of Lajoie, Baker, and Kanekiyo (supra) is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The provisional rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 44-63 of copending U.S. Application 19/077,674 in view of Lajoie, Baker, Kanekiyo, and Galarza et. al. (US20190030156A1, Priority 08/31/2015; hereafter “Galarza”) is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Pat. No. 11,192,926 in view of Kanekiyo (supra).
The instant claims and the ‘926 claims are both drawn towards nanostructures that are generated from polypeptides which assemble to display symmetrical structures, wherein said nanostructures may carry antigens from pathogens. The sets of claims are drawn towards methods of making and methods of using said nanostructures, especially using pharmaceutical or vaccine compositions which comprise the nanostructures in order to elicit a neutralizing immune response in a host against the pathogen. Both sets of claims are drawn to the same nanoparticle protein sequences forming the structural framework of the nanoparticle. Both are drawn to the amino acid linker sequence comprising a gly-ser linker, wherein SEQ ID NO: 56 of the ‘926 application is 100% identical to instant SEQ ID NO: 115. SEQ ID NO: 34 of ‘926 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 7 of ‘926. The main difference between the instant claims and the ‘926 claims is with the antigen delivered by the nanostructure. However, these differences would be obvious, given the prior art teachings of Kanekiyo, which teach the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles.
For at least these reasons, the ‘926 claims remain obvious over the instant claims, especially in view of Kanekiyo.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Pat. No. 11,732,011 in view of Lajoie, Kanekiyo, and Baker (supra).
The instant claims and the ‘011 claims are both drawn towards nanostructures that are generated from polypeptides which assemble to display symmetrical structures, wherein said nanostructures may carry antigens from viral pathogens. Both sets of claims are drawn toward the antigen and assembly polypeptide being heterologous fusion proteins. Both sets of claims are drawn towards pharmaceutical compositions which comprise the nanostructures. The sets of claims are drawn towards methods of making and methods of using said nanostructures, especially using pharmaceutical or vaccine compositions which comprise the nanostructures in order to elicit a neutralizing immune response in a host against the viral pathogen. Both sets of claims are drawn to the same nanoparticle protein sequences forming the structural framework of the nanoparticle. Both are drawn to the amino acid linker sequence comprising a gly-ser linker, wherein SEQ ID NO: 56 of the ‘011 application is 100% identical to instant SEQ ID NO: 115. SEQ ID NO: 34 of ‘011 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 7 of ‘011. The main difference between the instant claims and the ‘011 claims is with the antigen delivered by the nanostructure. However, these differences would be obvious, given the prior art teachings of Kanekiyo, which teach the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles.
For at least these reasons, the ‘011 claims remain obvious over the instant claims, especially in view of Kanekiyo.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of U.S. Pat. No. 12,275,757 in view of Kanekiyo (supra).
The instant claims and the ‘757 claims are both drawn towards nanostructures that are generated from polypeptides which assemble to display symmetrical structures, wherein said nanostructures may carry antigens from viral pathogens. Both sets of claims are drawn toward the antigen and assembly polypeptide being heterologous fusion proteins. Both sets of claims are drawn towards pharmaceutical compositions which comprise the nanostructures. The sets of claims are drawn towards methods of making and methods of using said nanostructures, especially using pharmaceutical or vaccine compositions which comprise the nanostructures in order to elicit a neutralizing immune response in a host against the viral pathogen. Both sets of claims are drawn to the same nanoparticle protein sequences forming the structural framework of the nanoparticle. Both are drawn to the amino acid linker sequence comprising a gly-ser linker, wherein SEQ ID NO: 56 of the ‘757 application is 100% identical to instant SEQ ID NO: 115. SEQ ID NO: 34 of ‘757 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 7 of ‘757. The main difference between the instant claims and the ‘757 claims is with the antigen delivered by the nanostructure. However, these differences would be obvious, given the prior art teachings of Kanekiyo, which teach the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles.
For at least these reasons, the ‘757 claims remain obvious over the instant claims, especially in view of Kanekiyo.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Pat. No. 9,630,994 in view of Kanekiyo (supra) and Chang et. al. (US20160208020A1; Pub. 07/21/2016; hereafter “Chang.”)
The instant claims and the ‘994 claims are both drawn towards nanostructures that are generated from polypeptides which assemble to display symmetrical structures, wherein said nanostructures may carry heterologous cargo. The instant claims and the ‘994 claims both provide for identical sequences within said nanostructure framework (e.g. reference and instant SEQ ID NO: 34 are 100% identical between both claims, reference and instant SEQ ID NO: 31 are 100% identical between both claims, etc.)
SEQ ID NO: 34 of ‘994 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 7 of ‘994. The main difference between the instant claims and the ‘994 claims is with the antigen delivered by the nanostructure, and the use of additional components, such as gly/ser linkers and self-cleaving peptide sequences within the nanoparticle subunits. However, these differences would be obvious, given the prior art teachings of Kanekiyo and Chang, which teach the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles. Chang teaches gly/ser linkers known in the art, and teaches SEQ ID NO: 10, which is 100% identical to instant SEQ ID NO: 116; as well as SEQ ID NO: 11, which is 100% identical to instant SEQ ID NO: 115 (See ABSS sequence alignments for us-18-359-154a-115.rai and us-18-359-154a-116.rai for the sequence of 14-997-764 for Chang).
For at least these reasons, the ‘994 claims remain obvious over the instant claims, especially in view of Kanekiyo and Chang.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Pat. No. 10,351,603 in view of Kanekiyo (supra) and Chang et. al. (US20160208020A1; Pub. 07/21/2016; hereafter “Chang”) as evidenced by Lajoie (supra).
The instant claims and the ‘603 claims are both drawn towards polypeptides which assemble to display symmetrical nanostructures. While the ‘603 claims do not provide specifically for the nanostructures in their claims, the ability for said proteins to form said nanostructures is inherent, as evidenced by the teachings of Lajoie, which teach the sequences of the ‘603 claims were known in the art for forming nanostructures that were capable of carrying heterologous cargo (see sequence analysis supra). The instant claims and the ‘603 claims both provide for identical sequences which formulate the nanostructure framework (e.g. reference and instant SEQ ID NO: 34 are 100% identical between both claims, reference and instant SEQ ID NO: 31 are 100% identical between both claims, etc.) SEQ ID NO: 34 of ‘603 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 7 of ‘603. The main difference between the instant claims and the ‘603 claims is with the antigen delivered by the proteins, and the use of additional components, such as gly/ser linkers and self-cleaving peptide sequences within the protein subunits. However, these differences would be obvious, given the prior art teachings of Kanekiyo and Chang, which teach the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles. Chang teaches gly/ser linkers known in the art, and teaches SEQ ID NO: 10, which is 100% identical to instant SEQ ID NO: 116; as well as SEQ ID NO: 11, which is 100% identical to instant SEQ ID NO: 115 (See ABSS sequence alignments for us-18-359-154a-115.rai and us-18-359-154a-116.rai for the sequence of 14-997-764 for Chang).
For at least these reasons, the ‘603 claims remain obvious over the instant claims, especially in view of Kanekiyo and Chang as evidenced by Lajoie.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Pat. No. 11,485,759 in view of Kanekiyo (supra) and Chang et. al. (US20160208020A1; Pub. 07/21/2016; hereafter “Chang”.)
The instant claims and the ‘759 claims are both drawn towards polypeptides which assemble to display symmetrical nanostructures. The instant claims and the ‘759 claims both provide for identical sequences which formulate the nanostructure framework (e.g. reference and instant SEQ ID NO: 34 are 100% identical between both claims, reference and instant SEQ ID NO: 31 are 100% identical between both claims, etc.) SEQ ID NO: 34 of ‘759 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 7 of ‘759. The main difference between the instant claims and the ‘759 claims is with the antigen delivered by the proteins, and the use of additional components, such as gly/ser linkers and self-cleaving peptide sequences within the protein subunits. However, these differences would be obvious, given the prior art teachings of Kanekiyo and Chang, which teach the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles. Chang teaches gly/ser linkers known in the art, and teaches SEQ ID NO: 10, which is 100% identical to instant SEQ ID NO: 116; as well as SEQ ID NO: 11, which is 100% identical to instant SEQ ID NO: 115 (See ABSS sequence alignments for us-18-359-154a-115.rai and us-18-359-154a-116.rai for the sequence of 14-997-764 for Chang).
For at least these reasons, the ‘759 claims remain obvious over the instant claims, especially in view of Kanekiyo and Chang as evidenced by Lajoie.
(New rejection – necessitated by amendment.) Claims 8-10, 20, 27, 35-36, and 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 14, 16-17, 22-24, and 29 of U.S. Pat. No. 12,433,943 in view of Lajoie, Kanekiyo (supra), and Chang et. al. (US20160208020A1; Pub. 07/21/2016; hereafter “Chang”.)
The instant claims and the ‘943 claims are both drawn towards nanostructures that are generated from polypeptides which assemble to display symmetrical structures, wherein said nanostructures may carry antigens from viral pathogens. Both sets of claims are drawn toward the antigen and assembly polypeptide being heterologous fusion proteins. Both sets of claims are drawn towards pharmaceutical compositions which comprise the nanostructures. Both sets of claims are drawn towards methods of making and methods of using said nanostructures, especially using pharmaceutical or vaccine compositions which comprise the nanostructures in order to elicit a neutralizing immune response in a host against the pathogen. With the amendments to the instant claims, the ‘943 claims and instant claims are drawn towards the same nanoparticle protein sequences. SEQ ID NO: 299 of ‘943 is 100% identical to instant SEQ ID NO: 34, and instant SEQ ID NO: 7 is 100% identical to SEQ ID NO: 1 of ‘943. The main differences between the instant claims and the ‘943 claims is the ‘943 claims specifically claim the antigen as being influenza HA while the instant claims provide for pathogenic surface protein antigens from EBV, namely gp350, and the use of additional components, such as gly/ser linkers and self-cleaving peptide sequences within the protein subunits. However, said differences would be obvious to a skilled artisan, given the teachings of Lajoie, Kanekiyo, and Chang.
The sequences of the ‘943 claims for the nanostructure-forming peptides and influenza HA proteins were known in the art, as evidenced by Lajoie (see sequence analysis supra), as were other viral surface proteins that could be substituted for the influenza HA, such as EBV gp350, as evidenced by Kanekiyo. Kanekiyo teaches the delivery of EBV gp350 antigen via self-assembling nanostructures, the use of flexible ser/gly linkers, and the use of self-cleaving peptides (all detailed supra). Kanekiyo teaches the fusion of EBV gp350 sequences to the surface of nanoparticles through fusion of the gp350 protein or immunogenic portions thereof to proteins known to self-assemble into nanoparticles. Chang teaches gly/ser linkers known in the art, and teaches SEQ ID NO: 10, which is 100% identical to instant SEQ ID NO: 116; as well as SEQ ID NO: 11, which is 100% identical to instant SEQ ID NO: 115 (See ABSS sequence alignments for us-18-359-154a-115.rai and us-18-359-154a-116.rai for the sequence of 14-997-764 for Chang).
For at least these reasons, the ‘943 claims remain obvious over the instant claims, especially in view of Lajoie, Kanekiyo, and Chang.
(Rejection withdrawn.) The rejection of Claims 8-10, 20, 27, 35-36, and 41-47 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,771,755 in view of Lajoie and Carfi (supra) is withdrawn in light of the filing and acceptance of a terminal disclaimer over the ‘755 patent.
Response to Arguments
Applicant's arguments filed 12/10/2025 regarding the non-statutory double patenting rejections have been fully considered but they are not entirely persuasive. While the previous rejections have been withdrawn in light of the amendments to the claims and the terminal disclaimer filed over the ‘755 patent, new rejections were made over some of the copending or patented claims in view of further teachings from Kanekiyo and/or Chang and/or Lajoie.
Applicant argues that none of the copending or patented claims render obvious the differences in light of the amendments to the claims. While this was persuasive with respect to some of the rejections, it was not persuasive for every rejection, for the reasons elaborated upon supra, as Kanekiyo teaches the use of flexible ser/gly linkers as well as self-cleaving sites. Chang teaches specific sequences for the ser/gly linkers which were not already rendered obvious by the copending or patented claims. Therefore, it remains for the reasons set forth supra that the copending claims are obvious variants of the noted copending or patented claims in view of the prior art.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/Primary Examiner, Art Unit 1671