DETAILED 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 18 December 2025 has been entered.
Application Status
This action is written in response to applicant’s correspondence received 18 December 2025. Claims 1 and 5-30 are currently pending. Claims 11-12 and 14-27 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1, 5-10, 13, and 28-30 are examined herein. The restriction requirement mailed 5 August 2021 is still deemed proper. Applicant's elected Group I, claims 1-10, without traverse in the reply filed 28 September 2021.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Japan on 4 April 2016. It is noted, however, that applicant has not filed a certified copy of the JP2016/001900 application as required by 37 CFR 1.55.
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.
Claim(s) 1, 5-10, 13, and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) in view of Simerska (Vaccine 32.37 (2014): 4743-4750) and Mekada (PG Pub No. US 2006/0288435 A1).
Regarding claim 1, Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid construct encoding an exosome that has a targeting moiety expressed on its surface, in the form of a fusion protein, such that the exosome can be loaded with exogenous genetic material and used in the delivery of nucleic acids for gene therapy and gene silencing (Col 2, lines 41-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36). Seow teaches that the targeting moiety may be short peptides that are heterologous to the exosome (Col. 7, lines 41-64). Seow does not teach or suggest that the nucleic acid construct comprises a sequence encoding a MHC.
Seow does not teach or suggest that the targeting moiety is a vaccine antigen (Claim 1). Seow does not teach or suggest that the CD81 exosome marker protein consists of the amino acids at position 1 to position 236 of the claimed SEQ ID NO: 12 (Claim 1).
However, one of ordinary skill in the art would have considered the teachings of Simerska and Mekada as both references are common fields of endeavor pertaining to the use of short peptides that can target heterologous proteins to induce immune responses and CD81 exosome marker proteins.
Simerska is directed towards a study concerned with ovalbumin lipid core peptide vaccines (Abstract). Simerska teaches that ovalbumin is a short peptide that can induce a CD8+ T cell response (pg. 4743-4744; see FIG. 1). Simerska teaches that targeting CD8+ cells with vaccines comprising ovalbumin peptides is important because CD8+ cells produce pro-inflammatory cytokines that help innate immune cells to eliminate numerous pathogens (pg. 4749).
Mekada is directed towards an invention concerned with the use of genes encoding for CD9 and CD81 genes in the generation of a non-human animal osteoporosis model animal (Abstract). Mekada teaches the use of a CD81 protein that has 100% sequence identity to the claimed SEQ ID NO: 12 ([0061]-[0062]; see SEQ ID NO: 11 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the targeting moiety and CD81 exosome marker protein of Seow for an ovalbumin targeting moiety, as described by Simerska, and a CD81 exosome marker protein having 100% identity to the claimed SEQ ID NO: 12, as described by Mekada. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a short heterologous targeting peptide that can be fused to a CD81 exosome while Simerska teaches that ovalbumin is a known short peptide sequence that can target specific cells and Mekada teaches that the claimed SEQ ID NO: 12 is a known CD81 amino acid sequence.
Regarding claim 5, Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36).
Regarding claim 6, it is noted that the specification teaches that “a vaccine antigen is an antigen with an ability to induce a response from the immune system when administered to a human or an animal. Such a response from the immune system can induce production of antibodies or activation of a certain type of cells (particularly 30 antigen presenting cells (e.g. , dendritic cells) , T lymphocytes, or B lymphocytes). In the present invention, examples thereof include, but are not limited to, cancer antigens for therapy targeting cancer. For example, an ovalbumin can be used as a model vaccine antigen.” (Instant specification; [0024]).
Simerska teaches that ovalbumin is a short peptide that can induce a CD8+ T cell response (pg. 4743-4744; see FIG. 1). Simerska teaches that CD8+ T cells are the principal effector cells for fighting cancer (pg. 4743).
Thus, the antigens of Simerska are directed towards cancer antigens as defined by the specification.
Regarding claim 7, Seow teaches that plasmid DNA may encode the fusion protein and be expressed within a target cell (Col. 11, lines 1-7).
Regarding claim 8, it is noted that the specification teaches that a DNA vaccine is plasmid DNA that is administered subcutaneously and can provide active immunity against a substance (Instant Specification; [0019]).
Seow teaches that the nucleic acid may be administered subcutaneously to a subject (Col. 12, lines 4-7). Simerska teaches that CD8+ T cells are the principal effector cells for fighting cancer (pg. 4743). Thus, the nucleic acid construct rendered obvious by Seow in view of Simerska and Mekada is directed towards a DNA vaccine that can provide active immunity against cancerous cells.
Regarding claim 9, Simerska teaches that ovalbumin is a short peptide that can induce a CD8+ T cell response (pg. 4743-4744; see FIG. 1). Simerska teaches that targeting CD8+ cells with vaccines comprising ovalbumin peptides is important because CD8+ cells produce pro-inflammatory cytokines that help innate immune cells to eliminate numerous pathogens (pg. 4749).
Regarding claim 10, Simerska teaches that CD8+ T cells are the principal effector cells for fighting cancer (i.e., the immunity is against cancer) (pg. 4743).
Regarding claim 13, Simerska teaches that ovalbumin is a short peptide that can induce a CD8+ T cell response (pg. 4743-4744; see FIG. 1). Simerska teaches that targeting CD8+ cells with vaccines comprising ovalbumin peptides is important because CD8+ cells produce pro-inflammatory cytokines that help innate immune cells to eliminate numerous pathogens (i.e., the antigen of Simerska is directed towards an immune response enhancer) (pg. 4749).
Regarding claim 28, the applicable teachings of Seow, Simerska, and Mekada are discussed above as applied to claim 1.
Seow teaches that the exosome marker protein may be CD9 (Col. 8, liens 23-30).
Mekada teaches the use of a CD9 exosome marker protein that comprises 100% identity to the claimed SEQ ID NO: 8 ([0061]-[0062]; see SEQ ID NO: 10 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the CD9 exosome marker protein of Seow for an exosome marker protein having 100% identity to the claimed SEQ ID NO: 8, as described by Mekada. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a CD9 exosome that can be fused to different targeting moieties while Mekada teaches that the claimed SEQ ID NO: 8 was a known CD9 exosome marker protein sequence.
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) in view of Simerska (Vaccine 32.37 (2014): 4743-4750) and Hisatomi (Photochemical & Photobiological Sciences 14.11 (2015): 1998-2006).
Regarding claim 29, Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid construct encoding an exosome that has a targeting moiety expressed on its surface, in the form of a fusion protein, such that the exosome can be loaded with exogenous genetic material and used in the delivery of nucleic acids for gene therapy and gene silencing (Col 2, lines 41-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36). Seow teaches that the nucleic acid can be used in immunization to express one or more antigens against which it is desired to produce an immune response (i.e., a vaccine antigen) (Col. 6, lines 47-54). Seow does not teach or suggest that the nucleic acid construct comprises a sequence encoding a MHC. Seow teaches that a glycine linker may be inserted between the exosome protein and targeting moiety (Col. 10, lines 48-60).
Seow does not teach or suggest that the targeting moiety is a vaccine antigen (Claim 29). Seow does not teach or suggest that the linker is a glycine hexamer (Claim 29).
However, one of ordinary skill in the art would have considered the teachings of Simerska and Hisatomi as both references are common fields of endeavor pertaining to the use of short peptides that can target heterologous proteins to induce immune responses and CD81 exosome marker proteins and glycine linkers.
Simerska is directed towards a study concerned with ovalbumin lipid core peptide vaccines (Abstract). Simerska teaches that ovalbumin is a short peptide that can induce a CD8+ T cell response (pg. 4743-4744; see FIG. 1). Simerska teaches that targeting CD8+ cells with vaccines comprising ovalbumin peptides is important because CD8+ cells produce pro-inflammatory cytokines that help innate immune cells to eliminate numerous pathogens (pg. 4749).
Hisatomi is drawn to a study concerned with the fusion of heterologous protein peptide sequences (Abstract). Hisatomi teaches that both YFP and mCh were able to be fused to heterologous proteins via the use of glycine hexamers (pg. 1999).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the targeting moiety and glycine linker of Seow for an ovalbumin targeting moiety, as described by Simerska, and a glycine hexamer, as described by Hisatomi. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a short heterologous targeting peptide that can be fused to a CD81 or CD9 exosome and have a glycine linker present between the peptide and exosome while Simerska teaches that ovalbumin is a known short peptide sequence that can target specific cells and Hisatomi teaches that the glycine hexamers were known in the art to be able to be linker sequences.
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) in view of Simerska (Vaccine 32.37 (2014): 4743-4750) and Mekada (PG Pub No. US 2006/0288435 A1), as applied to claims 1, 5-10, 13, and 28 above, further in view of Hisatomi (Photochemical & Photobiological Sciences 14.11 (2015): 1998-2006).
Regarding claim 30, Seow in view of Simerska and Mekada render obvious claims 1, 5-10, 13, and 28 as described above.
Seow in view of Simerska and Mekada does not teach or suggest the use of a glycine hexamer that is inserted as a linker between the exosome marker protein and vaccine antigen (Claim 30).
However, one of ordinary skill in the art would have considered the teachings of Hisatomi as both references are common fields of endeavor pertaining to the use of glycine linkers.
Hisatomi is drawn to a study concerned with the fusion of heterologous protein peptide sequences (Abstract). Hisatomi teaches that both YFP and mCh were able to be fused to heterologous proteins via the use of glycine hexamers (pg. 1999).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the glycine linker of Seow in view of Simerska and Mekada for a glycine hexamer, as described by Hisatomi. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow in view of Simerska and Mekada teaches the use of a short heterologous targeting peptide that can be fused to a CD81 or CD9 exosome and have a glycine linker present between the peptide and exosome while Hisatomi teaches that the glycine hexamers were known in the art to be able to be linker sequences.
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, 5-10, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-7 of US Patent No. 12,319,727 B2 in view of Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) in view of Simerska (Vaccine 32.37 (2014): 4743-4750) and Mekada (PG Pub No. US 2006/0288435 A1).
This is a provisional nonstatutory double patenting rejection.
Regarding instant claims 1, 5, and 9, patented claim 1 claims a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form. Patented claim 1 does not claim that the nucleic acid construct comprises a nucleic acid sequence encoding a MHC. Copending claim 5 claims that the exosome marker protein can be CD81 or CD9.
Patented claims 1 and 5 do not teach or suggest that the CD81 consists of the amino acids at position 1 to position 236 of SEQ ID NO:12 (Claim 1). Patented claims 1 and 5 do not teach or suggest that the DNA vaccine can induce Th1-type immunity that comprise an antigen-specific CD8+ T cell response (Claim 9).
However, one of ordinary skill in the art would have considered the teachings of Simerska and Mekada as the references are common fields of endeavor pertaining to the use of short peptides that can target heterologous proteins to induce immune responses and CD81 exosome marker proteins.
Simerska is directed towards a study concerned with ovalbumin lipid core peptide vaccines (Abstract). Simerska teaches that ovalbumin is a short peptide that can induce a CD8+ T cell response (pg. 4743-4744; see FIG. 1). Simerska teaches that targeting CD8+ cells with vaccines comprising ovalbumin peptides is important because CD8+ cells produce pro-inflammatory cytokines that help innate immune cells to eliminate numerous pathogens (i.e., ovalbumin peptide is a vaccine antigen) (pg. 4749).
Mekada is directed towards an invention concerned with the use of genes encoding for CD9 and CD81 genes in the generation of a non-human animal osteoporosis model animal (Abstract). Mekada teaches the use of a CD81 protein that has 100% sequence identity to the claimed SEQ ID NO: 12 ([0061]-[0062]; see SEQ ID NO: 11 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the copending CD81 exosome marker protein and vaccine antigen for the CD81 exosome marker protein of Mekada and the ovalbumin peptide of Simerska in order to induce Th1-type immunity that comprise an antigen-specific CD8+ T cell response, as further evidenced by Simerska. A person of ordinary skill in the art would have been motivated to do so in order to produce pro-inflammatory cytokines that help immune cells eliminate pathogens. A person of ordinary skill in the art would have had a reasonable expectation of success because both the patented claims and the references teach the use of functional CD81 exosome marker proteins and vaccine antigens.
Regarding instant claims 6, 10, and 13, patented claim 14 claims that the antigen is of a pathogen (i.e., the patented antigen can be a viral antigen that induces immunity against a viral disease).
Regarding instant claims 7-8, patented claim 7 claims that the nucleic acid construct is plasmid DNA (i.e., a DNA vaccine).
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 12,319,727 B2 in view of Mekada (PG Pub No. US 2006/0288435 A1).
Regarding instant claim 28, patented claim 1 claims a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form. Patented claim 4 claims that the exosome marker protein can be CD9.
Patented claims 1 and 4 do not teach or suggest that the exosome marker protein CD9 consists of amino acids at position 1 to 226 of SEQ ID NO: 8 (Claim 28).
However, one of ordinary skill in the art would have considered the teachings of Mekada as both references are common fields of endeavor pertaining to the use of CD9 exosome marker proteins.
Mekada is directed towards an invention concerned with the use of genes encoding for CD9 and CD81 genes in the generation of a non-human animal osteoporosis model animal (Abstract). Mekada teaches the use of a CD9 exosome marker protein that comprises 100% identity to the claimed SEQ ID NO: 8 ([0061]-[0062]; see SEQ ID NO: 10 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the CD9 exosome marker protein of patented claims 1 and 4 for an exosome marker protein having 100% identity to the claimed SEQ ID NO: 8, as described by Mekada. A person of ordinary skill in the art would have had a reasonable expectation of success because both the patented claims teach the use of CD9 exosome marker proteins that can be fused to different targeting moieties while Mekada teaches that the claimed SEQ ID NO: 8 was a known CD9 exosome marker protein sequence.
Claim 29 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 12,319,727 B2 in view of Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) and Hisatomi (Photochemical & Photobiological Sciences 14.11 (2015): 1998-2006).
Regarding instant claim 29, patented claim 1 claims a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form. Patented claim 1 does not claim that the nucleic acid construct comprises a nucleic acid sequence encoding a MHC. Patented claim 4 claims that the exosome marker protein can be CD81.
Patented claims 1 and 4 do not teach or suggest the use of a glycine hexamer that is inserted as a linker between the exosome marker protein and the vaccine antigen (Claim 29).
However, one of ordinary skill in the art would have considered the teachings of Seow and Mekada as both references are common fields of endeavor pertaining to the use of exosome marker proteins and the fusions of exosome marker proteins to a vaccine antigen.
Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid construct encoding an exosome that has a targeting moiety expressed on its surface, in the form of a fusion protein, such that the exosome can be loaded with exogenous genetic material and used in the delivery of nucleic acids for gene therapy and gene silencing (Col 2, lines 41-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36). Seow teaches that the nucleic acid can be used in immunization to express one or more antigens against which it is desired to produce an immune response (i.e., a vaccine antigen) (Col. 6, lines 47-54). Seow does not teach or suggest that the nucleic acid construct comprises a sequence encoding a MHC. Seow teaches that a glycine linker may be inserted between the exosome protein and targeting moiety (Col. 10, lines 48-60).
Hisatomi is drawn to a study concerned with the fusion of heterologous protein peptide sequences (Abstract). Hisatomi teaches that both YFP and mCh were able to be fused to heterologous proteins via the use of glycine hexamers (pg. 1999).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the exosome marker protein of patented claims 1 and 4 such that a glycine hexamer was inserted as a linker between the exosome marker protein and the vaccine antigen, as described by Seow and Hisatomi. A person of ordinary skill in the art would have been motivated to do so in order to utilize a linker that was known in the art to be able to link to heterologous peptide sequences to one another, as described by Seow. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a short heterologous targeting peptide that can be fused to a CD81 exosome and have a glycine linker present between the peptide and exosome while Hisatomi teaches that the glycine hexamers were known in the art to be able to be linker sequences between heterologous peptides.
Claim 30 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 12,319,727 B2 in view of Mekada (PG Pub No. US 2006/0288435 A1), as applied above to claim 28, further in view of Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) and Hisatomi (Photochemical & Photobiological Sciences 14.11 (2015): 1998-2006).
Regarding instant claim 30, patented claims 1 and 4 of US Patent No. 12,319,727 B2 in view of Mekada renders obvious claim 28.
Patented claims 1 and 4 in view of Mekada do not teach or suggest the use of a glycine hexamer that is inserted as a linker between the exosome marker protein and the vaccine antigen (Claim 30).
However, one of ordinary skill in the art would have considered the teachings of Seow and Mekada as both references are common fields of endeavor pertaining to the use of exosome marker proteins and the fusions of exosome marker proteins to a vaccine antigen.
Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid construct encoding an exosome that has a targeting moiety expressed on its surface, in the form of a fusion protein, such that the exosome can be loaded with exogenous genetic material and used in the delivery of nucleic acids for gene therapy and gene silencing (Col 2, lines 41-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36). Seow teaches that the nucleic acid can be used in immunization to express one or more antigens against which it is desired to produce an immune response (i.e., a vaccine antigen) (Col. 6, lines 47-54). Seow does not teach or suggest that the nucleic acid construct comprises a sequence encoding a MHC. Seow teaches that a glycine linker may be inserted between the exosome protein and targeting moiety (Col. 10, lines 48-60).
Hisatomi is drawn to a study concerned with the fusion of heterologous protein peptide sequences (Abstract). Hisatomi teaches that both YFP and mCh were able to be fused to heterologous proteins via the use of glycine hexamers (pg. 1999).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the exosome marker protein of patented claims 1 and 4 in view of Mekada such that a glycine hexamer was inserted as a linker between the exosome marker protein and the vaccine antigen, as described by Seow and Hisatomi. A person of ordinary skill in the art would have been motivated to do so in order to utilize a linker that was known in the art to be able to link to heterologous peptide sequences to one another, as described by Seow. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a short heterologous targeting peptide that can be fused to a CD9 exosome and have a glycine linker present between the peptide and exosome while Hisatomi teaches that the glycine hexamers were known in the art to be able to be linker sequences between heterologous peptides.
Claims 1, 6-10, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-8, and 14 of US Patent No. 12,209,115.
This is a provisional nonstatutory double patenting rejection.
Regarding instant claims 1 and 13, patented claim 1 claims a method of enhancing an immune response in a subject comprising administering to the subject an effective amount of a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form. Patented claim 4 claims that the exosome marker protein is CD31. Patented claim 1 does not claim that the nucleic acid construct comprises a nucleic acid sequence encoding a MHC.
Regarding instant claim 6, patented claim 6 claims identical limitations.
Regarding claim 7, patented claim 7 claims identical limitations.
Regarding instant claims 8, patented claim 7 claims that the nucleic acid construct is plasmid DNA (i.e., a DNA vaccine).
Regarding claim 9, patented claim 8 claims identical limitations.
Regarding claims 10, and 13, patented claim 14 claims that the antigen is of a pathogen (i.e., the patented antigen can be a viral antigen that induces immunity against a viral disease).
Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-8, and 14 of US Patent No. 12,209,115 B2, as applied to claims 1, 6-10, and 13 above, further in view of patented claim 4 and Mekada (PG Pub No. US 2006/0288435 A1).
This is a provisional nonstatutory double patenting rejection.
Regarding instant claim 5 patented claims 1, 6-8, and 14 anticipate claims 1, 6-10, and 13 as described above. Patented claim 4 further claims that the exosome marker protein may be CD81.
Patented claims 1, 4, 6-8, and 14 do not teach or suggest that the CD81 consists of the amino acids at position 1 to position 236 of SEQ ID NO:12 (Claim 1).
However, one of ordinary skill in the art would have considered the teachings of Mekada as both references are common fields of endeavor pertaining to the use of CD81 exosome marker proteins.
Mekada is directed towards an invention concerned with the use of genes encoding for CD9 and CD81 genes in the generation of a non-human animal osteoporosis model animal (Abstract). Mekada teaches the use of a CD81 protein that has 100% sequence identity to the claimed SEQ ID NO: 12 ([0061]-[0062]; see SEQ ID NO: 11 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the patented CD81 exosome marker protein for a CD81 exosome marker protein having 100% identity to the claimed SEQ ID NO: 12, as descried by Mekada. A person of ordinary skill in the art would have had a reasonable expectation of success because both the patented claims and the references teach the use of functional CD81 exosome marker proteins that can be fused to vaccine antigens.
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 12,209,115 B2 in view of Mekada (PG Pub No. US 2006/0288435 A1).
Regarding instant claim 28, patented claim 1 claims a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form. Patented claim 4 claims that the exosome marker protein can be CD9.
Patented claims 1 and 4 do not teach or suggest that the exosome marker protein CD9 consists of amino acids at position 1 to 226 of SEQ ID NO: 8 (Claim 28).
However, one of ordinary skill in the art would have considered the teachings of Mekada as both references are common fields of endeavor pertaining to the use of CD9 exosome marker proteins.
Mekada is directed towards an invention concerned with the use of genes encoding for CD9 and CD81 genes in the generation of a non-human animal osteoporosis model animal (Abstract). Mekada teaches the use of a CD9 exosome marker protein that comprises 100% identity to the claimed SEQ ID NO: 8 ([0061]-[0062]; see SEQ ID NO: 10 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the CD9 exosome marker protein of patented claims 1 and 4 for an exosome marker protein having 100% identity to the claimed SEQ ID NO: 8, as described by Mekada. A person of ordinary skill in the art would have had a reasonable expectation of success because both the patented claims teach the use of CD9 exosome marker proteins that can be fused to different targeting moieties while Mekada teaches that the claimed SEQ ID NO: 8 was a known CD9 exosome marker protein sequence.
Claim 29 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 12,209,115 B2 in view of Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) and Hisatomi (Photochemical & Photobiological Sciences 14.11 (2015): 1998-2006).
Regarding instant claim 29, patented claim 1 claims a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form. Patented claim 1 does not claim that the nucleic acid construct comprises a nucleic acid sequence encoding a MHC. Patented claim 4 claims that the exosome marker protein can be CD81.
Patented claims 1 and 4 do not teach or suggest the use of a glycine hexamer that is inserted as a linker between the exosome marker protein and the vaccine antigen (Claim 29).
However, one of ordinary skill in the art would have considered the teachings of Seow and Mekada as both references are common fields of endeavor pertaining to the use of exosome marker proteins and the fusions of exosome marker proteins to a vaccine antigen.
Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid construct encoding an exosome that has a targeting moiety expressed on its surface, in the form of a fusion protein, such that the exosome can be loaded with exogenous genetic material and used in the delivery of nucleic acids for gene therapy and gene silencing (Col 2, lines 41-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36). Seow teaches that the nucleic acid can be used in immunization to express one or more antigens against which it is desired to produce an immune response (i.e., a vaccine antigen) (Col. 6, lines 47-54). Seow does not teach or suggest that the nucleic acid construct comprises a sequence encoding a MHC. Seow teaches that a glycine linker may be inserted between the exosome protein and targeting moiety (Col. 10, lines 48-60).
Hisatomi is drawn to a study concerned with the fusion of heterologous protein peptide sequences (Abstract). Hisatomi teaches that both YFP and mCh were able to be fused to heterologous proteins via the use of glycine hexamers (pg. 1999).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the exosome marker protein of patented claims 1 and 4 such that a glycine hexamer was inserted as a linker between the exosome marker protein and the vaccine antigen, as described by Seow and Hisatomi. A person of ordinary skill in the art would have been motivated to do so in order to utilize a linker that was known in the art to be able to link to heterologous peptide sequences to one another, as described by Seow. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a short heterologous targeting peptide that can be fused to a CD81 exosome and have a glycine linker present between the peptide and exosome while Hisatomi teaches that the glycine hexamers were known in the art to be able to be linker sequences between heterologous peptides.
Claim 30 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of US Patent No. 12,209,115 B2 in view of Mekada (PG Pub No. US 2006/0288435 A1), as applied above to claim 28, further in view of Seow (US Patent No. 10,233,445 B2, filed 8 September 2015) and Hisatomi (Photochemical & Photobiological Sciences 14.11 (2015): 1998-2006).
Regarding instant claim 30, patented claims 1 and 4 of US Patent No. 12,209,115 B2 in view of Mekada renders obvious claim 28.
Patented claims 1 and 4 in view of Mekada do not teach or suggest the use of a glycine hexamer that is inserted as a linker between the exosome marker protein and the vaccine antigen (Claim 30).
However, one of ordinary skill in the art would have considered the teachings of Seow and Mekada as both references are common fields of endeavor pertaining to the use of exosome marker proteins and the fusions of exosome marker proteins to a vaccine antigen.
Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid construct encoding an exosome that has a targeting moiety expressed on its surface, in the form of a fusion protein, such that the exosome can be loaded with exogenous genetic material and used in the delivery of nucleic acids for gene therapy and gene silencing (Col 2, lines 41-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins) that include CD81 and tetraspanins (Col. 8, lines 17-36). Seow teaches that the nucleic acid can be used in immunization to express one or more antigens against which it is desired to produce an immune response (i.e., a vaccine antigen) (Col. 6, lines 47-54). Seow does not teach or suggest that the nucleic acid construct comprises a sequence encoding a MHC. Seow teaches that a glycine linker may be inserted between the exosome protein and targeting moiety (Col. 10, lines 48-60).
Hisatomi is drawn to a study concerned with the fusion of heterologous protein peptide sequences (Abstract). Hisatomi teaches that both YFP and mCh were able to be fused to heterologous proteins via the use of glycine hexamers (pg. 1999).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the exosome marker protein of patented claims 1 and 4 in view of Mekada such that a glycine hexamer was inserted as a linker between the exosome marker protein and the vaccine antigen, as described by Seow and Hisatomi. A person of ordinary skill in the art would have been motivated to do so in order to utilize a linker that was known in the art to be able to link to heterologous peptide sequences to one another, as described by Seow. A person of ordinary skill in the art would have had a reasonable expectation of success because Seow teaches the use of a short heterologous targeting peptide that can be fused to a CD9 exosome and have a glycine linker present between the peptide and exosome while Hisatomi teaches that the glycine hexamers were known in the art to be able to be linker sequences between heterologous peptides.
Response to Arguments
Insofar as Applicant’s arguments are directed towards the references utilized in the newly recited 35 USC 103 and double patenting rejections of record, the arguments have been fully considered but they are not persuasive.
Applicant’s arguments with respect to the previously utilized Ramos and Maecker references (see pg. 6-7) are not found persuasive because they are directed towards references that are not being relied upon in the current rejection.
Applicant alleges that Hisatomi is non-analogous art (see pg. 8).
This argument is not found persuasive because Seow in view of Simerska and Mekada that a glycine linker may be inserted between the exosome marker protein and the vaccine antigen. Hisatomi teaches that glycine hexamers are glycine linkers that can link heterologous peptide sequences to one another. Accordingly, Hisatomi and Seow in view of Simerska and Mekada are directed towards analogous art that utilize glycine linkers to link two heterologous peptide sequences to one another.
Conclusion
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636