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 .
DETAILED ACTION
Applicant’s election with traverse of Group I, claims 74-87 in the reply filed on March 31, 2026 is acknowledged.
Applicant’s election with traverse of the species: 1) cancer an breast cancer as the specific disease; 2) lumazine synthase-Spy tag as the specific first polynucleotide; 3) HER2-SpyCatcher as the specific second polynucleotide, is acknowledged.
Applicant traversed the restriction by challenging the analysis that the common technical features do not make a contribution over prior art as set forth in the previous Office Action of February 3, 2026. However, Applicant did not explicitly point out why the Examiner’s analysis is improper. As further illustrated in 103 rejection below, the common technical features do not make a contribution over prior art. Thus the requirement is still deemed proper and is therefore made FINAL.
Claims 74-93 are pending.
Claims 78-80, and 88-93 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 74-77, and 81-87 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of International Application No. PCT/EP2021/086528 filed 12/17/2021, which claims priority to EP Patent Application No. 21161436.7 filed 03/09/2021 and EP Patent Application No. 20215653.5 filed 12/18/2020.
Certified copies of foreign priority applications have been received as required by 37 CFR 1.55.
The priority date has been established as December 18, 2020 for the claims under consideration.
Information Disclosure Statement
The Information Disclosure Statements filed on 09/05/2023, 12/21/2023, 12/21/2023, 12/21/2023 and 07/15/2024 have been considered and entered by examiner.
Claim Rejections - 35 USC § 112(b)
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 74-77, and 81-87 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 74 recites “administering a composition comprising…” (not “administering a composition to the subject wherein the composition comprises …”) which is ambiguous and can be refer to applying the composition to a system or a process. Using “administering” without a target allows for broader interpretations of use. For example, any step of applying the claimed composition could read on “administering a composition”.
Claim 84 recites the limitation “one or more first peptide tags are fused to…” and “one or more second peptide tags are fused to…”. There is insufficient antecedent basis for these limitations in the claim because claim 74 recites “fused to a first peptide tag” and “fused to a second peptide tag”.
Claim 84 recites options (i), (ii) without explicitly using connecting word (and, or) which cause ambiguities in scope. The claim can be interpreted as requiring all listed elements ((i) and (ii)) to be present simultaneously, or requiring only (i) or (ii).
Regarding claim 87, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 75-77, 81-83, 85 and 86 are also rejected because these claims depend on claim 74 directly or indirectly.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 74-77, and 81-87 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
These claims are drawn to “a method of treatment and/or prophylaxis of a disease in a subject in need thereof comprising the step of administering a composition comprising: i. a first polynucleotide encoding a protein fused to a first peptide tag; and ii. a second polynucleotide encoding an antigen fused to a second peptide tag, wherein the antigen and the protein upon expression in a cell are linked via an isopeptide bond between the first peptide tag and the second peptide tag, whereby i - ii form a particle displaying said antigen”. Given Broadest Reasonable Interpretation (BRI), the claim would encompass:
A broad genus of proteins encoded by the first polynucleotide. The claim does not limit the claimed protein, thus, the protein can be any protein with any function (e.g. both particle-forming or non-particle-forming proteins).
A broad genus of antigens encoded by the second polynucleotide. The claim does not limit the claimed antigen, thus, the antigen can be any peptide-based antigen with any function.
Taken together, the claims encompass a broad genus of composition comprising (i) and (ii) which vary significantly; have different structures, different physical and chemical properties; and have different functions. However, the specification lacks written description support for the broadly claimed genera.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. (See Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, especially page 1106 3rd column). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP 2163 II.A.3a.ii.
Regarding the claimed protein, paragragh [0099] of the instant publication US 2024/0108718 A1 discloses that the nucleic acid based vaccine which upon delivery into eukaryotic cells during vaccination, are translated into self-assembling nanoparticles, displaying the vaccine antigen in a unidirectional repetitive and multivalent manner by exploiting a split-protein Tag/Catcher conjugation. The examples demonstrate several particle-forming proteins, such as AP205, HBc, i301, Ferritin, 2-oxo acid dehydrogenase subunit E2, lumazine synthase, norovirus capsid protein, which can form particles and are able to couple with antigens (Examples 6 and 7). Example 9 further shows that coupling between the particle and the antigens occurs intracellularly. As evidenced by Nguyen (Nguyen et al., npj Vaccines (2021) 6:70, Publication Date: 05/13/2021), only a few proteins can form particles and display antigens, see Table 1. The particle-forming proteins disclosed in the instant specification and prior art would not tell other proteins (including non-particle-forming proteins) encompassed in the claim with the required functions and properties, e.g. forming particles and displaying antigens.
Regarding the claimed antigen, the claims encompass all possible peptide-based antigens which may not associated with any disease, e.g. eGFP , His purification tag, as evidenced by instant claim 87. One of ordinary skill in the art would not be able to readily recognize/visualize which antigens (encompassed by the claims, such as eGFP and His tag) can be used in the claimed method to treat and prophylaxis a disease.
In addition, the claims identify the composition, protein and/or antigen by function only, where the function is to:
Treat or prophylaxis a disease (claims 74 and 85);
Form a particle and display antigen (claim 74)
Protein is a particle-forming protein (claim 77)
Antigen is associate with or specific for an abnormal physiological response (claim 86)
The specification and prior art have not established the relationship between the claimed functions and the structure of composition, protein and/or antigen. One of ordinary skilled in the art would not be able to readily recognize/visualize composition, protein and/or antigen with required properties. Taken together, applicant has not provided sufficient evidence to show that the inventors possess a genus of composition, protein and/or antigen which can be used in the claimed method.
Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai
Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent
Applications under the 35 USC §112 paragraph 1, "Revision 1" of Written Description
Requirement (66 FR 1099-1111, March 25, 2008) state, "[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention (Id. At 1104). Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the
Applicant described distinguishing identifying characteristics sufficient to show that
Applicant were in possession of the claimed invention at the time the application was filed.
Taken together, the instant specification has not provided a sufficient description showing the necessary functional characteristics coupled with a known or disclosed correlation between functions and the structure. Thus, the specification is not sufficient to show the applicant was in possession of the genus of composition, protein and/or antigen broadly encompassed for the claimed method.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 74-77, and 82-87 are rejected under 35 U.S.C. 103 as being unpatentable over Pedersen (Pedersen et al., WO 2016/112921 A1, Publication Date: 07/21/2016, in IDS of 09/05/2023), in view of Zakeri (Zakeri, et al., PNAS, E690-E697, Publication Date: 02/24/2012, in IDS of 09/05/2023) and Verbeke (Verbeke et al., Nano Today 28 (2019), 100766, Publication Date: 08/23/2019).
Pedersen teaches a method of treating and/or preventing a clinical condition in a subject in need thereof comprising administering a composition (page 8, lines 1-6), wherein said composition is a pharmaceutical composition comprising a vaccine which comprises a virus capsid protein comprising a first peptide tag and an antigen fused to a second peptide tag, wherein the antigen and virus capsid protein are linked vis an isopeptide bond between the first and second peptide tag, and wherein the two protein molecules for a virus-like particle (VLP) displaying said antigen (page 4, lines 28-33; page 5, lines 1-3).
Pedersen teaches that the SpyTag and SpyCatcher interact via spontaneous isopeptide bond formation, and the isopeptide bond ensures consistent orientation of the antigens this displayed on the VLP (page 4, para. 3).
Pedersen teaches a composition comprising said vaccine as well as host cell expressing the first and second polypeptide encoded by said first and second polynucleotides (page 6, lines 19-26; page 7, lines 1-5; page 57, lines 6-25; page 62, lines 1-10).
Pedersen teaches a vector comprising the first polynucleotide encoding a virus capsid protein (e.g. AP205) with s Spytag and a second polynucleotide encoding an antigen fused to SpyCatcher (page 59, lines 16-20; page 75, lines 4-22).
Pedersen teaches expression of fusion protein and antigen in E.coli BL21 or JM109 by transforming plasmid to the host cell (the bridging paragraph of page 75-76; paras 2-3 on page 76).
Pedersen teaches that VLPs (e.g. SpyTag-AP205) can display a variety of antigens (e.g. SpyCatcher-antigen), see Table 5 on pages 79-81.
Pedersen teaches that VLP-based antigen presentation platform can be used to induce antibodies with increased avidity compared to corresponding soluble protein vaccines in vivo (Fig. 17, Fig. 18, and § Immunological testing of the VLP-based antigen presentation platform, on pages 81-84).
Pedersen teaches that mice were immunized with VLP-displayed self-antigens induce antigen specific antibodies, whereas immunization with the non-displayed soluble self-antigen did not induce antigen-specific antibodies (page 86, paras. 1-3).
Pedersen teaches that the VLP-presented antigen vaccine (e.g. for antigen Pfs25, HER2 or PCSK9) are effective for functional antibodies (page 87).
Pedersen teaches as set forth above. However, Pedersen does not teach administering the nucleotides to the subject directly or the tags linked via an isopeptide bond in a cell.
Zakeri teaches that SpyTag and SpyCatcher form an isopeptide bond in minutes and in diverse conditions of pH, temperature, and buffer (Abstract).
Zakeri teaches SpyTag can be fused at either terminus or internally (Abstract).
Zakeri teaches that SpyTag and SpyCatcher can react inside cells. Cells were transformed with a plasmid encoding the proteins individually or bicistronically, induced with IPTG, and subsequently boiled with SDS loading buffer to prevent any ex vivo reaction. Lysates were then analyzed by SDS-PAGE. A covalent complex corresponding to the expected molecular weight of SpyCatcher:SpyTag-MBP could be clearly observed and little unreacted SpyTag-MBP remained (page E693, col. 1, para. 1; and Fig. 4A).
Verbeke teaches mRNA can be used as vaccine, and many mRNAs vaccines entered the clinical trial stage (see Abstract; the last paragraph of Introduction; and Table 1).
Verbeke teaches that mRNA offers a valuable and safe alternative to plasmid DNA. Indeed, as the mRNA molecules only have to reach the cytosol in order to be translated at the ribosomes, they avert the risk of being integrated into the host genome (page 2, col. 1, para. 1). mRNA represents a versatile and promising platform for vaccination (page 14, col. 1, para. 2).
Verbeke teaches lipid nanoparticle (LNP) for mRNA delivery which provides several advantages, such as a reduced toxicity, a prolonged blood circulation lifetime, an improved stability, and/or an improved uptake of mRNA (the bridging paragraph of pages 6-7, and Fig. 4).
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of Pedersen, Zakeri and Berbeke, to develop a mRNA vaccine in lipid nanoparticle formulation wherein the mRNA encoding (i) a VLP (e.g. SpyTag-AP205) and (ii) an antigen (e.g. SpyCatcher-HER2, the elected antigen) for treating and/or HER2 associated conditions (e.g. cancers) by administering the mRNA vaccine to a subject. One of ordinary skill in the art would have a reasonable expectation of success because 1) the SpyTag-VLPs and SpyCatcher-antigen can efficiently display antigen and induce antigen-specific antibody in vivo (taught by Pedersen); 2) the SpyTag and Spycatcher can form isopeptide bond quickly in cells (taught by Zakeri); 3) mRNA is a versatile and promising platform for vaccination and mRNA-LNP formulation provides several advantages (taught by Verbeke); and 4) mRNA-LNP formulation are well-known in the art and have been widely used in clinical filed. The motivation would have been to expand the options for vaccines and to develop a more versatile process for vaccination.
Regarding claims 82 and 83, Pedersen teaches that SpyTag and SpyCatcher (the elected species) have the sequence of SEQ ID NO: 36 and SEQ ID NO: 37, respectively (page 111), also see claims 7, 21, 31
As shown below, SEQ ID NO: 36 and SEQ ID NO: 37 of Pedersen are identical to SEQ ID NO: 1 and SEQ ID NO: 21 of instant application, respectively.
SEQ ID NO: 36 of Pedersen vs. SEQ ID NO: 1 of instant application
Query Match 100.0%; Score 68; DB 1; Length 13;
Best Local Similarity 100.0%;
Matches 13; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AHIVMVDAYKPTK 13
|||||||||||||
Db 1 AHIVMVDAYKPTK 13
SEQ ID NO: 37 of Pedersen vs. SEQ ID NO: 21 of instant application
Query Match 100.0%; Score 595; DB 1; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAMVDTLSGLSSEQGQSGDMTIEEDSATHIKFSKRDEDGKELAGATMELRDSSGKTISTW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAMVDTLSGLSSEQGQSGDMTIEEDSATHIKFSKRDEDGKELAGATMELRDSSGKTISTW 60
Qy 61 ISDGQVKDFYLYPGKYTFVETAAPDGYEVATAITFTVNEQGQVTVNGKATKGDAHI 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ISDGQVKDFYLYPGKYTFVETAAPDGYEVATAITFTVNEQGQVTVNGKATKGDAHI 116
Regarding claim 84, Pedersen teaches SpyCatcher fused to the N-term of antigens and DNA encoding the fusion protein (Table 6 on pages 88-89; and SEQ ID NO: 48- SEQ ID NO: 54 on pages 113-115). Pedersen teaches SpyTag fused to the N-term of AP205 and nucleic acid encoding the fusion protein (SEQ ID NO: 62 of page 116; SEQ ID NO: 63 on page 117).
Regarding claims 85 and 86, Pedersen teaches that the vaccine can be used to treat cancer (claim 15), and the antigen is a polypeptide, peptide and/or an antigenic fragment of a polypeptide associated with an abnormal physiological response (claim 24).
Claim 81 is rejected under 35 U.S.C. 103 as being unpatentable over Pedersen (Pedersen et al., WO 2016/112921 A1, Publication Date: 07/21/2016, in IDS of 09/05/2023), in view of Zakeri (Zakeri, et al., PNAS, E690-E697, Publication Date: 02/24/2012, in IDS of 09/05/2023) and Verbeke (Verbeke et al., Nano Today 28 (2019), 100766, Publication Date: 08/23/2019), as applied to claims 74-77 and 82-87 above, and further in view of Zhang (Zhang et al., Scientific Reports, (2020) 10:18149, Publication Date: 10/23/2020) and Kanekiyo (Kanekiyo et al., US 2016/0303224 A1, Publication Date: 10/20/2016).
Pedersen, Zakeri and Verbeke teach claims 74 and 77 as set forth above. However, Pedersen, Zakeri and Verbeke do not teach the particle forming protein is a lumazine synthase as set forth in SEQ ID NO: 70 (the elected species).
Zhang teaches that antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines (Abstract).
Zhang teaches a plug-and-play using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the Aquifex aeolicus lumazine synthase (LuS) (Abstract, Fig. 1b, Fig. 2a, Fig. 4a and Fig. 5a) which have a virus-particle-like structure.
Zhang teaches that the nanoparticle system induces strong immune response in vivo (Fig. 6a-6c).
Zhang teaches that lumazine-based system are suitable for mammalian expression allowing for post-translational modifications (the first paragraph of Discussion).
Kanekiyo teaches vaccine comprise nanoparticles that display antigen (envelope protein from EMV) on their surface. The nanoparticles comprise a self-assembly protein, such as lumazine synthase (Abstract, [0087]). Representative examples of such self-assembly proteins including Aquifex aeolicus lumazine synthase: SEQ ID NO: 26 (Table 2 on page 9). As shown below, SEQ ID NO: 26 of Kanekiyo is identical to SEQ ID NO: 70 of instant application:
SEQ ID NO: 26 of Kanekiyo vs. SEQ ID NO: 70 of instant application
Query Match 100.0%; Score 774; Length 154;
Best Local Similarity 100.0%;
Matches 154; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDCIVRHGGREEDITLVRVPGSWEIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDCIVRHGGREEDITLVRVPGSWEIP 60
Qy 61 VAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLANLSLELRKPITFGVITADT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLANLSLELRKPITFGVITADT 120
Qy 121 LEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR 154
||||||||||||||||||||||||||||||||||
Db 121 LEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR 154
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of Pedersen, Zakeri and Verbeke with Zhang and Kanekiyo and to substitute particle forming protein: AP205 with Aquifex aeolicus lumazine synthase of SEQ ID NO: 70 as taught by Zhang and Kanekiyo. One of ordinary skill in the art would have had a reasonable expectation of success with the substitution because: 1) Aquifex aeolicus lumazine synthase of SEQ ID NO: 70 are self-assembling protein which form a virus-like particles; 2) antigens can be displayed on the surface of the particle; 3) antigen-displaying particles induce strong immune response; 4) lumazine synthase has been tested in SpyTag:SpyCatcher system in vivo. The motivation would have been to expand the options for vaccine and to develop a nanoparticle vaccine suitable for mammalian system.
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 74-77, and 82-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,526,376 B2 (hereinafter Pat. 376) in view of Pedersen (Pedersen et al., WO 2016/112921 A1, Publication Date: 07/21/2016, in IDS of 09/05/2023), Zakeri (Zakeri, et al., PNAS, E690-E697, Publication Date: 02/24/2012, in IDS of 09/05/2023) and Verbeke (Verbeke et al., Nano Today 28 (2019), 100766, Publication Date: 08/23/2019).
The claims of Pat. 376 teach a vaccine for use in the prophylaxis and/or treatment of a disease wherein the vaccine comprises: i. a virus capsid protein comprising a first peptide tag, and ii. an antigen fused to a second peptide tag, wherein the antigen and virus capsid protein are linked via an isopeptide bond between the first and second peptide tag, and wherein i-ii form a virus-like particle displaying said antigen on its surface (claim 1).
The claims of Pat. 376 teach the vaccine according to claim 1, wherein the first peptide tag comprises a SpyTag, and wherein the second peptide tag comprises a SpyCatcher, wherein the antigen and virus capsid protein are linked via the interaction between the SpyCatcher and SpyTag interaction, and wherein i-ii form a virus-like particle displaying said antigen (claim 2).
The claims of Pat. 376 teach the vaccine according to claim 1, wherein the virus capsid protein comprises or consists of an AP205 capsid protein and wherein the first peptide tag is one or more SpyTags (claim 5).
The claims of Pat. 376 teach the vaccine according to claim 5, wherein the SpyCatcher or SpyTag is fused to the antigen in a position selected from the group consisting of the N-terminal end, the C-terminal end, or inserted in-frame into the coding sequence of the antigen (claim 7).
The claims of Pat. 376 teach the vaccine according to claim 1, wherein the disease is selected from the group consisting of a cancer, a cardiovascular disease, an immune-inflammatory disease, a chronic disease, a neurological disease and/or an infectious disease (claim 10).
The claims of Pat. 376 teach wherein the antigen is selected from the group consisting of interleukin-17, hemagglutinin, GD2, EGF-R, CEA, CD52, CD21, human melanoma protein gp100, human melanoma protein melan-A/MART1, tyrosinase, NA17-A nt, MAGE-3, HPV 16 E7, HPV L2, PD1, PD-L1, CTLA-4, p53, hCG, Fel d1 and (IHNV) G-protein or an antigenic fragment hereof (claim 12).
The claims of Pat. 376 teach a vector system comprising at least one polynucleotide encoding i. an AP205 capsid protein comprising an N terminal SpyCatcher, according to claim 1, and ii. an antigen fused to a SpyTag or KTag. It is noted that the vector system of Pat. 376 reads on the composition of instant claim 74, but don’t teach to administering the polynucleotides to the subject.
Although the claims of Pat. 376 teach a vector system comprising at least one polynucleotide encoding i. an AP205 capsid protein comprising an N terminal SpyCatcher and ii. an antigen fused to a SpyTag, the claims of Pat. 376 do not teach administering the nucleotides to the subject directly or the tags linked via an isopeptide bond in a cell.
Pedersen, Zakeri and Verbeke teach instant claims 74-77 and 82-87as set forth above. Particularly, Pedersen teaches that the SpyTag and SpyCatcher interact via spontaneous isopeptide bond formation, and the isopeptide bond ensures consistent orientation of the antigens this displayed on the VLP (page 4, para. 3). Pedersen teaches that VLPs (e.g. SpyTag-AP205) can display a variety of antigens (e.g. SpyCatcher-antigen), see Table 5 on pages 79-81. Zakeri teaches that SpyTag and SpyCatcher can react inside cells (page E693, col. 1, para. 1; and Fig. 4A). Verbeke teaches that mRNA offers a valuable and safe alternative to plasmid DNA. Indeed, as the mRNA molecules only have to reach the cytosol in order to be translated at the ribosomes, they avert the risk of being integrated into the host genome (page 2, col. 1, para. 1). mRNA represents a versatile and promising platform for vaccination (page 14, col. 1, para. 2).
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of the claims of Pat. 376, Pedersen, Zakeri and Berbeke, to develop a mRNA vaccine in lipid nanoparticle formulation wherein the mRNA encoding (i) a VLP (e.g. SpyTag-AP205) and (ii) an antigen (e.g. SpyCatcher-HER2, the elected antigen) for treating and/or HER2 associated conditions (e.g. cancers) by administering the mRNA vaccine to a subject. One of ordinary skill in the art would have a reasonable expectation of success because 1) the SpyTag-VLPs and SpyCatcher-antigen can efficiently display antigen and induce antigen-specific antibody in vivo (taught by Pedersen); 2) the SpyTag and Spycatcher can form isopeptide bond quickly in cells (taught by Zakeri); 3) mRNA is a versatile and promising platform for vaccination and mRNA-LNP formulation provides several advantages (taught by Verbeke); and 4) mRNA-LNP formulation are well-known in the art and have been widely used in clinical filed. The motivation would have been to expand the options for vaccines and to develop a more versatile process for vaccination.
Claims 74-77, and 82-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,086,056 B2 (hereinafter Pat. 800) in view of Pedersen (Pedersen et al., WO 2016/112921 A1, Publication Date: 07/21/2016, in IDS of 09/05/2023), Zakeri (Zakeri, et al., PNAS, E690-E697, Publication Date: 02/24/2012, in IDS of 09/05/2023) and Verbeke (Verbeke et al., Nano Today 28 (2019), 100766, Publication Date: 08/23/2019).
The claims of Pat. 056 teach an immunogenic virus-like particle having a surface, comprising: a. an AP205 capsid protein as set forth in SEQ ID NO: 58 or a biologically active variant thereof having at least 95% sequence identity to SEQ ID NO: 58, further comprising a first peptide tag, and b. a HER2 antigen as set forth in SEQ ID NO: 18 or a variant thereof having at least 90% sequence identity to SEQ ID NO: 18, further comprising a second peptide tag, wherein the HER2 antigen or variant thereof and the AP205 virus capsid protein or variant thereof are linked via an isopeptide bond between the first and second peptide tag, wherein the HER2 antigen is present on the surface of the immunogenic virus-like particle, and wherein the first peptide tag and the second peptide tag together represent a peptide tag pair (claim 1).
The claims of Pat. 056 teach the immunogenic virus-like particle according to claim 1, wherein the peptide tag pair is selected from the group consisting of i) a SpyTag and SpyCatcher pair, and … (claims 2-4); wherein the first peptide tag is fused to the N-terminal end or to the C-terminal end of the capsid protein by a linker (claim 7)
The claims of Pat. 056 teach an isolated host cell expressing, the immunogenic virus-like particle of claim 1 (claim 12). It is obviously the host cell would comprise a first polynucleotide encoding component (a) of claim 1 and a second polynucleotide encoding component (b) of claim 1. However, the claims of Pat.056 do not teach administering the polynucleotides to the subject.
The claims of Pat. 056 teach a method of treatment of a cancer in a subject in need thereof, comprising: providing an immunogenic composition comprising at least one immunogenic virus-like particle according to claim 1, and administering said immunogenic virus-like particle to said subject (claim 14).
Although the claims of Pat. 056 teach a host cell comprising at least one polynucleotide encoding i. an AP205 fused with a tag and ii. an HER2 fused to a tag for making immunogenic virus-like particles, the claims of Pat. 056 do not teach administering the nucleotides to the subject directly or the tags linked via an isopeptide bond in a cell.
Pedersen, Zakeri and Verbeke teach instant claims 74-77 and 82-87 as set forth above. Particularly, Pedersen teaches that the SpyTag and SpyCatcher interact via spontaneous isopeptide bond formation, and the isopeptide bond ensures consistent orientation of the antigens this displayed on the VLP (page 4, para. 3). Pedersen teaches that VLPs (e.g. SpyTag-AP205) can display a variety of antigens (e.g. SpyCatcher-antigen), see Table 5 on pages 79-81. Zakeri teaches that SpyTag and SpyCatcher can react inside cells (page E693, col. 1, para. 1; and Fig. 4A). Verbeke teaches that mRNA offers a valuable and safe alternative to plasmid DNA. Indeed, as the mRNA molecules only have to reach the cytosol in order to be translated at the ribosomes, they avert the risk of being integrated into the host genome (page 2, col. 1, para. 1). mRNA represents a versatile and promising platform for vaccination (page 14, col. 1, para. 2).
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of the claims of Pat. 056, Pedersen, Zakeri and Berbeke, to develop a mRNA vaccine in lipid nanoparticle formulation wherein the mRNA encoding (i) a VLP (e.g. SpyTag-AP205) and (ii) an antigen (e.g. SpyCatcher-HER2, the elected antigen) for treating and/or HER2 associated conditions (e.g. cancers) by administering the mRNA vaccine to a subject. One of ordinary skill in the art would have a reasonable expectation of success because 1) the SpyTag-VLPs and SpyCatcher-antigen can efficiently display antigen and induce antigen-specific antibody in vivo (taught by Pedersen); 2) the SpyTag and Spycatcher can form isopeptide bond quickly in cells (taught by Zakeri); 3) mRNA is a versatile and promising platform for vaccination and mRNA-LNP formulation provides several advantages (taught by Verbeke); and 4) mRNA-LNP formulation are well-known in the art and have been widely used in clinical filed. The motivation would have been to expand the options for vaccines and to develop a more versatile process for vaccination.
Claims 74-77, and 82-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,497,800 B2 (hereinafter Pat. 800) in view of Pedersen (Pedersen et al., WO 2016/112921 A1, Publication Date: 07/21/2016, in IDS of 09/05/2023), Zakeri (Zakeri, et al., PNAS, E690-E697, Publication Date: 02/24/2012, in IDS of 09/05/2023) and Verbeke (Verbeke et al., Nano Today 28 (2019), 100766, Publication Date: 08/23/2019).
The claims of Pat. 800 teach A vaccine for use in the prophylaxis and/or treatment of a disease wherein the vaccine comprises: i. a virus capsid protein comprising a first peptide tag, and ii. an antigen fused to a second peptide tag, wherein the antigen and virus capsid protein are linked via an isopeptide bond between the first and second peptide tag, and wherein i-ii form a virus-like particle displaying said antigen (claim 1).
The claims of Pat. 800 teach the vaccine according to claim 1, wherein the first peptide tag comprises a SpyTag, and wherein the second peptide tag comprises a SpyCatcher, wherein the antigen and virus capsid protein are linked via the interaction between the SpyCatcher and SpyTag interaction, and wherein i-ii form a virus-like particle displaying said antigen (claim 2); wherein the virus capsid protein comprises an AP205 capsid protein (claim 3), wherein the SpyCatcher is fused to N-terminal end of the AP205 (claim 4), wherein the disease can be cancer (claim 10), wherein the antigen can be a cancer-specific polypeptide (claim 11), such as IL-2, EFGR, CEA (claim 12).
The claims of Pat. 800 teach a host cell expressing i. a first polynucleotide encoding a virus capsid protein comprising a first peptide tag; and/or ii. a second polynucleotide encoding an antigen fused to a second peptide tag, wherein the antigen and virus capsid protein are linked via an isopeptide bond between the first and second peptide tag, and wherein i-ii form a virus-like particle displaying said antigen (claim 14). Thus, the claims of Pat. 800 teach composition comprising (i) and (ii) of instant claim 74, but don’t teach to administering the polynucleotides to the subject.
The claims of Pat. 800 teach the host cell according to claim 14, wherein the first peptide tag comprises a SpyTag, and wherein the second peptide tag comprises a SpyCatcher (claim 15), the antigen can be a cancer-specific polypeptide (claim 17), such as IL-2, EFGR, CEA (claim 18).
Although the claims of Pat. 800 teach a host cell comprising at least one polynucleotide encoding i. an AP205 capsid protein comprising an N terminal SpyCatcher and ii. an antigen fused to a SpyTag, the claims of Pat. 800 do not teach administering the nucleotides to the subject directly or the tags linked via an isopeptide bond in a cell.
Pedersen, Zakeri and Verbeke teach instant claims 74-77 and 82-87 as set forth above. Particularly, Pedersen teaches that the SpyTag and SpyCatcher interact via spontaneous isopeptide bond formation, and the isopeptide bond ensures consistent orientation of the antigens this displayed on the VLP (page 4, para. 3). Pedersen teaches that VLPs (e.g. SpyTag-AP205) can display a variety of antigens (e.g. SpyCatcher-antigen), see Table 5 on pages 79-81. Zakeri teaches that SpyTag and SpyCatcher can react inside cells (page E693, col. 1, para. 1; and Fig. 4A). Verbeke teaches that mRNA offers a valuable and safe alternative to plasmid DNA. Indeed, as the mRNA molecules only have to reach the cytosol in order to be translated at the ribosomes, they avert the risk of being integrated into the host genome (page 2, col. 1, para. 1). mRNA represents a versatile and promising platform for vaccination (page 14, col. 1, para. 2).
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of the claims of Pat. 800, Pedersen, Zakeri and Berbeke, to develop a mRNA vaccine in lipid nanoparticle formulation wherein the mRNA encoding (i) a VLP (e.g. SpyTag-AP205) and (ii) an antigen (e.g. SpyCatcher-HER2, the elected antigen) for treating and/or HER2 associated conditions (e.g. cancers) by administering the mRNA vaccine to a subject. One of ordinary skill in the art would have a reasonable expectation of success because 1) the SpyTag-VLPs and SpyCatcher-antigen can efficiently display antigen and induce antigen-specific antibody in vivo (taught by Pedersen); 2) the SpyTag and Spycatcher can form isopeptide bond quickly in cells (taught by Zakeri); 3) mRNA is a versatile and promising platform for vaccination and mRNA-LNP formulation provides several advantages (taught by Verbeke); and 4) mRNA-LNP formulation are well-known in the art and have been widely used in clinical filed. The motivation would have been to expand the options for vaccines and to develop a more versatile process for vaccination.
Claims 74-77, and 82-87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-50 of copending Application No. 17/968,115 (hereinafter, Appl. 115) in view of Pedersen (Pedersen et al., WO 2016/112921 A1, Publication Date: 07/21/2016, in IDS of 09/05/2023), Zakeri (Zakeri, et al., PNAS, E690-E697, Publication Date: 02/24/2012, in IDS of 09/05/2023) and Verbeke (Verbeke et al., Nano Today 28 (2019), 100766, Publication Date: 08/23/2019).
The claims of Appl. 115 teach an immunogenic composition comprising: a) a virus capsid protein comprising a first peptide tag, wherein the virus capsid protein comprises an AP205 capsid protein, and b) an antigen fused to a second peptide tag, wherein the antigen is HER2 or an antigenic fragment thereof, wherein the antigen and virus capsid protein are linked via an isopeptide bond between the first and second peptide tag, wherein a)-b) form a particle displaying said antigen (claim 47).
The claims of Appl. 115 teach a method for the prophylaxis and/or treatment of a disease in a subject in need thereof, comprising administering to the subject the composition of claim 47, wherein the disease is a cancer,… (claim 48).
The claims of Appl. 115 teach a vaccine comprising a) a virus capsid protein comprising a first peptide tag, and b) HER-2 or an antigenic fragment thereof fused to a second peptide tag, wherein the antigen and virus capsid protein are linked via an isopeptide bond between the first and second peptide tag, and wherein a)-b) form a virus-like particle displaying HER2 or the antigenic fragment thereof (claim 50).
Thus, the claims of Appl. 115 are drawn to polypeptide-based vaccine and method of using the vaccine to treat and/or prevent diseases. The claims of Appl. 115 do not teach using the polynucleotide encoding the polypeptide-based vaccine directly for treating or preventing diseases, or the tags linked via an isopeptide bond in a cell.
Pedersen, Zakeri and Verbeke teach instant claims 74-77 and 82-87 as set forth above. Particularly, Pedersen teaches that the SpyTag and SpyCatcher interact via spontaneous isopeptide bond formation, and the isopeptide bond ensures consistent orientation of the antigens this displayed on the VLP (page 4, para. 3). Pedersen teaches that VLPs (e.g. SpyTag-AP205) can display a variety of antigens (e.g. SpyCatcher-antigen), see Table 5 on pages 79-81. Zakeri teaches that SpyTag and SpyCatcher can react inside cells (page E693, col. 1, para. 1; and Fig. 4A). Verbeke teaches that mRNA offers a valuable and safe alternative to plasmid DNA. Indeed, as the mRNA molecules only have to reach the cytosol in order to be translated at the ribosomes, they avert the risk of being integrated into the host genome (page 2, col. 1, para. 1). mRNA represents a versatile and promising platform for vaccination (page 14, col. 1, para. 2).
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine the teachings of the claims of Appl. 115, Pedersen, Zakeri and Berbeke, to develop a mRNA vaccine in lipid nanoparticle formulation wherein the mRNA encoding (i) a VLP (e.g. SpyTag-AP205) and (ii) an antigen (e.g. SpyCatcher-HER2, the elected antigen) for treating and/or HER2 associated conditions (e.g. cancers) by administering the mRNA vaccine to a subject. One of ordinary skill in the art would have a reasonable expectation of success because 1) the SpyTag-VLPs and SpyCatcher-antigen can efficiently display antigen and induce antigen-specific antibody in vivo (taught by Pedersen); 2) the SpyTag and SpyCatcher can form isopeptide bond quickly in cells (taught by Zakeri); 3) mRNA is a versatile and promising platform for vaccination and mRNA-LNP formulation provides several advantages (taught by Verbeke); and 4) mRNA-LNP formulation are well-known in the art and have been widely used in clinical filed. The motivation would have been to expand the options for vaccines and to develop a more versatile process for vaccination.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/ Supervisory Patent Examiner, Art Unit 1642
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