20DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of species of SEQ ID NO: 2 in the reply filed on 5/27/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-14 with the elected species of SEQ ID NO: 2 are considered.
Claim Objections
Claim 3 is objected to because of the following informalities: Please spell out all abbreviations cited in claim, which include Qp, MS2 or AP205 . Appropriate correction is required.
Claims 3-5 are objected because the SEQ ID NO: 1 is the sequence of S1 protein of SARS-CoV-2 rather than the capsid protein of the claimed capsid of phage MP205 with 100% identity.
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 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6, 7-12 of copending Application No. 18, 267, 379 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the conflict claims are obvious each from other rather than patentable distinct each from other .
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
In the instant case, both of the rejected claims are directed to a soluble pathogen-like antigen (PLA) complex comprising: (1) a virus-like particle (VLP), which is self-assembled by a first fusion protein comprising a viral capsid protein or a variant thereof at its N-terminus, SpyTag at its C-terminus, and a first linker peptide linking both; (2) a second fusion protein, comprising an antigen or a variant thereof, SpyCatcher and a second linker peptide linking both, preferably the SpyCatcher is at the N-terminus of the second fusion protein; wherein the virus-like particle also encapsulates nucleic acid inside it, and wherein the virus-like particle and the second fusion protein are covalently connected through the SpyCatcher and the SpyTag, so that the antigen or a variant thereof is displayed on the surface of the virus- like particle. In particular, wherein the capsid protein is from Escherichia coli phage Qp, MS2 or AP205, preferably from Escherichia coli phage AP205, wherein the sequence of the capsid protein of the phage AP205 has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 1, other hand the capsid protein, wherein the antigen is selected from RBD sequence of S protein of SARS-CoV2 virus, wherein the antigen is a RBD sequence of the S1 protein of SARS-CoV2 virus. wherein the sequence of the antigen has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% %, 98%, 99% or 100% identity with SEQ ID NO: 2 of SEQ ID NO: 24. wherein the antigen is a RBD sequence of the S1 protein of SARS-CoV2 virus. wherein the sequence of the SpyTag has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with of SEQ ID NO: 3, and the sequence of the SpyCatcher has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 4. The soluble pathogen-like antigen complex according to claim 1, wherein in the first fusion protein, the phage capsid protein or a variant thereof is linked with the SpyTag via a first linker peptide, and in the second fusion protein, the antigen or a variant thereof is linked to the SpyCatcher via a second linker peptide. wherein in the first fusion protein, the phage capsid protein or a variant thereof is linked with the SpyTag via a first linker peptide, and in the second fusion protein, the antigen or a variant thereof is linked to the SpyCatcher via a second linker peptide. The soluble pathogen-like antigen complex according to claim 10, wherein the sequence of the first linker peptide is SEQ ID NO: 5, and the sequence of the second linker peptide is SEQ ID NO: 6.
The reference claims are directed a soluble pathogen-like antigen (PLA) complex comprising: (1) a virus-like particle (VLP), which is self-assembled by a first fusion protein comprising a viral capsid protein or a variant thereof at its N-terminus, SpyTag at its C-terminus, and a first linker peptide linking both; (2) a second fusion protein, comprising an antigen or a variant thereof, SpyCatcher and a second linker peptide linking both, preferably the SpyCatcher is at the N-terminus of the second fusion protein; wherein the virus-like particle also encapsulates nucleic acid inside it, and wherein the virus-like particle and the second fusion protein are covalently connected through the SpyCatcher and the SpyTag, so that the antigen or a variant thereof is displayed on the surface of the virus- like particle, wherein the capsid protein is from Escherichia coli phage Qp, MS2 or AP205, preferably from Escherichia coli phage AP205, which is the same capsid protein cited in the rejected claim 3, in particularly which has same amino acid sequence wherein one scope of the antigen is selected from RBD sequence of S1 protein of SARS-CoV2 virus, wherein the RBD is same antigen cited in the rejected claim 6. Furthermore, the reference claims 6-10 are also directed to the same amino acid sequences of SpyTag, SpyCatcher, the first and second peptide inker respectively.
An obviousness-type double-patenting rejection is appropriate where the conflict claims are not identical but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim(s) is either anticipated by or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 14U F.3d 1428, 46 USPQZd 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQZd 2010 (Fed. either anticipated by, 1993); In re Longi, F.2d 887, 225 US/Q 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
In the instant case, reference and rejected claims are obvious each from other although they are not cited as an identical virus particle in term wherein the first peptide linker and second peptide linker is connected to the SpyTag and SpyCatcher respectively, wherein the reference claims are more specifically cited at the C terminals vs the rejected claims without specified locations. But the two sets of claims comprise same structural limitations
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 1-3, 6, 10, 13-14 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Quinlan et al. (bioRxiv 2020, Nov. 18, Vol. 11, 18.388934. [Version 1] doi: 10.1101/2020.11.18.388934).
Quinlian et al. teach a method for making S1 antigenic protein of SARS-Cov-2 as a nanoparticle or virus-like particle, wherein the antigen if the S1 antigen of SARS—CoV-2 , particularly comprising either its receptor binding domain (RBD) and/or a proline-stabilized S-protein ectodomain by fusing either of the proteinic antigens with at their C-termini to a SpyTag followed by either conjugating to either SpyCatcher-mi3 particles (A) via an isopeptide bond formation by a peptide linkage, or KLH peptide linkage (B) (Fig. 2). Quinlian et al. also teach using the virus-like particle or nanoparticle of the RBD/SpyTg-SpyCatcher complex and formulated as an immunogenic composition to induce an immune responses in animals successfully after formulated the RBA/SpyTag/SpyCatcher with other pharmaceutically accepted carrier and excipients (See Figs 1-5 and describes in Materials and Methods as well as Results and Discussion
The more detail explanation why RBD or proline-stabilized S-protein ectodomain fused and/or conjugated to SpyTag /SpyCatcher is called as a nanoparticle or virus-like particle inherently is evidenced by Bruun et al. (ACS NANO published in 2018, pp. 8855-8866, please see Abstract and Figs.1 and 2, as well as pp. 8855-8856). This document has described how to making the antigen as nano scaffold or nanoparticle or virus-like particle by the SpyTag/SpyCatcher technology in detail, which is the method followed by the cited reference by Quinlan et al. hereinto. More specifically, the method is the one for expression of SpyCatcher-AP250 VLP by C41 E Coli cells and they concluded that these Plug-and-Display platforms were based on SpyTag or SpyCatcher linked to the coat protein cp3 from the bacteriophage AP205. Spy-AP205 VLPs have been investigated as vaccine candidates against a number of targets, including malaria and cancer (See pp. 8861-8862).
Regarding the ratio cited in the claim 12, the Bruun et al. also teach at Figure 3. That SpyCatcher-mi3 nanoparticles efficiently reacted with a variety of antigens. Conjugation was performed with SpyCatcher-mi3 in a 1:3 ratio with antigen . This meets the limitation cited as less than or equal to 1:1 .
Therefore, Claims 1-3, 6, 10, 12-14 are anticipated by Quinlian et al.
Claims 1-3, 6-7, 9-10, 13-14 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Zeng, et al. (CN 111991556 B).
Zeng et al. teach nanoparticle and a composition comprising the same , wherein the nanoparticle is made by a population of an immunogenic complexes comprising a fusion protein formed by covalently linking components a) and b) through SpyCatcher-SpyTag; a) Component is a nanoparticle carrier obtained by self-assembly of the recombinant polypeptide obtained by SpyCatcher through the fusion and expression of the GGSGGSGGSGGS connecting peptide and the N-terminus of the I53-50 carrier protein; The amino acid sequence of the SpyCatcher is shown in SEQ ID NO: 7, which meets the claimed SEQ ID NO: 4 explicitly and counterpart or SkyTag implicitly. The carrier protein I53-50 is assembled from a trimer I53-50A1.1PT1 and a pentamer I53-50B.PT1, and I53-50A1.1PT1 and a pentamer I53-50B.PT1 is shown in SEQ ID NO: 4, the amino acid sequence of I53-50B.4P.1 is shown in SEQ ID NO: 5; b) Component is a recombinant polypeptide obtained by SpyTag fused to the C-terminus of the RBD antigen of the SARS-CoV-2 virus through the GSGSGSGSG linking peptide; The amino acid sequence of the RBD antigen is shown in SEQ ID NO: 1, and the amino acid sequence of the SpyTag is shown in SEQ ID NO: 6. 2 . A nanoparticle vaccine comprising the immunogenic complex of claim 1 . 3 . 3. The nanoparticle vaccine according to claim 2, further comprising a pharmaceutically acceptable carrier and/or adjuvant. 4. The nanoparticle vaccine according to claim 3, wherein the adjuvant is Sigma Adjuvant System and/or AddaVax. 5. A kit, characterized in that, comprising the nanoparticle vaccine of any one of claims 2 to 4, and a container for inoculating the nanoparticle vaccine. 6. the preparation method of the immunogenic complex of claim 1, is characterized in that, comprises: Express the recombinant polypeptides in component a) and component b), co-incubate after purification, and self-assemble the immunogenic complex obtained. 7. The immunogenic compound of claim 1, or the application of the nanoparticle vaccine of any one of claims 2 to 4 in the preparation of a medicine for preventing novel coronavirus pneumonia. Moreover, Zeng et al. also disclose an amino acid sequence of the RBD antigen with at least 99.6% identical to the claimed SEQ ID NO: 2. They also teach that an expressing the recombinant polypeptides in component a) and component b), co-incubate after purification, and self-assemble the immunogenic complex obtained an immunogenic composition and used it as a nanoparticle vaccine of any one of claims 2 to 4 in the preparation of a medicine for preventing novel coronavirus pneumonia. To this context, the cited reference anticipates claims 1-2, 6-7, 9-10 and 13-14 implicitly and explitely.
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 1-10 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Quinlan et al. (bioRxiv 2020, Nov. 18, Vol. 11, 18.388934) and further in view of US Patent No. 11382968 to George and CN 111,991,556 to Zeng et al.
The rejected claims are drawn to a soluble pathogen-like antigen complex comprising: (1) a virus-like particle (VLP), which is self-assembled by a first fusion protein comprising a viral capsid protein or a variant thereof at its N-terminus and SpyTag at its C-terminus, (2) a second fusion protein, comprising an antigen from S1 protein of SARS-CoV2 virus or a variant thereof and SpyCatcher, preferably the SpyCatcher is at the N-terminus of the second fusion protein; wherein, the virus-like particle also encapsulates nucleic acid inside it, and wherein the virus-like particle and the antigen from the S1 protein of SARS-CoV2 virus are covalently connected through the SpyCatcher and the SpyTag, so that the antigen from S1 protein of SARS-CoV2 virus or a variant thereof is displayed on the surface of the virus-like particle, wherein the soluble pathogen-like antigen complex according to claim 1, wherein the nucleic acid encapsulated in the virus-like particle is the nucleic acid which is encapsulated by the virus-like particle when self-assembling and is from host bacteria used to express the virus-like particles, preferably the host bacteria is Escherichia coli, and preferably the nucleic acid is RNA; the soluble pathogen-like antigen complex according to claim 1,wherein the capsid protein is from Escherichia coli phage Qp, MS2 or AP205, preferably from Escherichia coli phage AP205 with an amino acid sequence of at least 90% to the SEQ ID NO: 1, wherein the antigen is a RBD sequence of the S1 protein of SARS-CoV2 virus, with at least 90% to the SEQ ID NO: 2 and the SpyTag with at least 90% to SEQ ID NO; 3 and SpyCatcher with 90% to SEQ ID NO: 4 , the rejected claim 14 is also directed to the method for using the same.
Quinlian et al. teach a method for making S1 antigenic protein of SARS-Cov-2 as a nanoparticle or virus-like particle, wherein the antigen if the S1 antigen of SARS—CoV-2 , particularly comprising either its receptor binding domain (RBD) and/or a proline-stabilized S-protein ectodomain by fusing either of the proteinic antigens with at their C-termini to a SpyTag followed by either conjugating to either SpyCatcher-mi3 particles (A) via an isopeptide bond formation by a peptide linkage, or KLH peptide linkage (B) (Fig. 2). Quinlian et al. also teach using the virus-like particle or nanoparticle of the RBD/SpyTg-SpyCatcher complex and formulated as an immunogenic composition to induce an immune responses in animals successfully after formulated the RBA/SpyTag/SpyCatcher with other pharmaceutically accepted carrier and excipients (See Figs 1-5 and describes in Materials and Methods as well as Results and Discussion
The more detail explanation why RBD or proline-stabilized S-protein ectodomain fused and/or conjugated to SpyTag /SpyCatcher is called as a nanoparticle or virus-like particle inherently is evidenced by Bruun et al. (ACS NANO published in 2018, pp. 8855-8866, please see Abstract and Figs.1 and 2, as well as pp. 8855-8856). This document has described how to making the antigen as nano scaffold or nanoparticle or virus-like particle by the SpyTag/SpyCatcher technology in detail, which is the method followed by the cited reference by Quinlan et al. hereinto. More specifically, the method is the one for expression of SpyCatcher-AP250 VLP by C41 E Coli cells and they concluded that these Plug-and-Display platforms were based on SpyTag or SpyCatcher linked to the coat protein cp3 from the bacteriophage AP205. Spy-AP205 VLPs have been investigated as vaccine candidates against a number of targets, including malaria and cancer (See pp. 8861-8862).
Regarding the ratio cited in the claim 12, the Bruun et al. also teach at Figure 3. That SpyCatcher-mi3 nanoparticles efficiently reacted with a variety of antigens. Conjugation was performed with SpyCatcher-mi3 in a 1:3 ratio with antigen . This meets the limitation cited as less than or equal to 1:1 .
Quinlian et al. do not disclose the sequence of the Escherichia coli phage AP205, the S1 antigenic sequence comprising at least 90% to the SEQ ID NO: 2 and SpyTag and SpyCatcher sequences.
Zeng et al. teach nanoparticle and a composition comprising the same , wherein the nanoparticle is made by a population of an immunogenic complexes comprising a fusion protein formed by covalently linking components a) and b) through SpyCatcher-SpyTag; a) Component is a nanoparticle carrier obtained by self-assembly of the recombinant polypeptide obtained by SpyCatcher through the fusion and expression of the GGSGGSGGSGGS connecting peptide and the N-terminus of the I53-50 carrier protein; The amino acid sequence of the SpyCatcher is shown in SEQ ID NO: 7, which meets the claimed SEQ ID NO: 4 explicitly and counterpart or SkyTag implicitly. The carrier protein I53-50 is assembled from a trimer I53-50A1.1PT1 and a pentamer I53-50B.PT1, and I53-50A1.1PT1 and a pentamer I53-50B.PT1 is shown in SEQ ID NO: 4, the amino acid sequence of I53-50B.4P.1 is shown in SEQ ID NO: 5; b) Component is a recombinant polypeptide obtained by SpyTag fused to the C-terminus of the RBD antigen of the SARS-CoV-2 virus through the GSGSGSGSG linking peptide; The amino acid sequence of the RBD antigen is shown in SEQ ID NO: 1, and the amino acid sequence of the SpyTag is shown in SEQ ID NO: 6. 2 . A nanoparticle vaccine comprising the immunogenic complex of claim 1 . 3 . 3. The nanoparticle vaccine according to claim 2, further comprising a pharmaceutically acceptable carrier and/or adjuvant. 4. The nanoparticle vaccine according to claim 3, wherein the adjuvant is Sigma Adjuvant System and/or AddaVax. 5. A kit, characterized in that, comprising the nanoparticle vaccine of any one of claims 2 to 4, and a container for inoculating the nanoparticle vaccine. 6. the preparation method of the immunogenic complex of claim 1, is characterized in that, comprises: Express the recombinant polypeptides in component a) and component b), co-incubate after purification, and self-assemble the immunogenic complex obtained. 7. The immunogenic compound of claim 1, or the application of the nanoparticle vaccine of any one of claims 2 to 4 in the preparation of a medicine for preventing novel coronavirus pneumonia. Moreover, Zeng et al. also disclose an amino acid sequence of the RBD antigen with at least 99.6% identical to the claimed SEQ ID NO: 2. They also teach that an expressing the recombinant polypeptides in component a) and component b), co-incubate after purification, and self-assemble the immunogenic complex obtained an immunogenic composition and used it as a nanoparticle vaccine of any one of claims 2 to 4 in the preparation of a medicine for preventing novel coronavirus pneumonia. To this context, the cited reference anticipates claims 1-2, 6-7, 9-10 and 13-14 implicitly and explitely. But Zeng et al. does not teach the amino acid sequence of the S1 antigen with 100% identity to the claimed SEQ ID NO: 2.
US Patent No. 11382968 to George et al. teaches an amino acid sequence of S1 antigenic protein with 100% to the claimed SEQ ID NO: 2.
Therefore, it would have been obvious for any person with an ordinarily skilled in the art to be motivated by the cited references and using the already known amino acid sequences for the RBD S1 antigen sequence, the SpyTag and SpyCatcher sequence well known in the art prior to the current Application was filed to make and use the nanoparticle or virus like particle of RBD/SpyTag/SpyCatcher with a reasonable expectation of success. As there are no unexpected results have been provided, hence the claimed invention as a whole is prima facie obvious absence unexpected results.
Conclusion
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671
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