Office Action 1: Non-Final Rejection (2024-07-29)
Rejection types: 102 - Lack of Novelty, 103 - Obviousness, Double Patenting

CLAIMS:
AMENDMENTS TO THE CLAIMS

This listing of claims will replace all prior versions and listings of claims in the application.

Listing of Claims:

1-16. Canceled215

17\. (New) 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.

18\. (New) The nucleic acid construct of claim 17, wherein the exosome marker protein is a protein that is present in a membrane of an exosome.

19\. (New) The nucleic acid construct of claim 17, wherein the exosome marker protein belongs to the tetraspanin family.

20\. (New) The nucleic acid construct of claim 17, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.

21\. (New) The nucleic acid construct of claim 17, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.

22\. (New) The nucleic acid construct of claim 17, wherein the antigen is of a pathogen.

23\. (New) The nucleic acid construct of claim 17, wherein the nucleic acid construct is a plasmid DNA.

24\. (New) The nucleic acid construct of claim 17, wherein the expressed protein is present in an exosome.

25\. (New) A protein in a form of a vaccine antigen protein fused with an exosome marker protein.

26\. (New) The protein of claim 25, wherein the exosome marker protein is a protein that is present in a membrane of an exosome.

27\. (New) The protein of claim 25, wherein the exosome marker protein belongs to the tetraspanin family.

28\. (New) The protein of claim 25, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.

29\. (New) The protein of claim 25, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.

30\. (New) The protein of claim 25, wherein the antigen is of a pathogen.

31\. (New) An exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.

32\. (New) The exosome of claim 31, wherein the exosome marker protein is a protein that is present in a membrane of an exosome.

33\. (New) The exosome of claim 31, wherein the exosome marker protein belongs to the tetraspanin family.

34\. (New) The exosome of claim 31, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.

35\. (New) The exosome of claim 31, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.

36\. (New) The exosome of claim 31, wherein the antigen is of a pathogen.

OFFICE ACTION:
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 .
Application Status
This action is written in response to applicant’s correspondence received 30 January 2024. Claims 17-36 are pending. Accordingly, claims 17-36 are currently under examination.
Information Disclosure Statement
The information disclosure statements filed 11 August 2023 and 30 January 2024 have been considered.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 17, 22-25, 30-31, and 36 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ramos (PG Pub No. US 2017/0274062 A1, filed 8 May 2015).
Regarding claims 17, 22-25, 30-31, and 36, Ramos is drawn to an invention concerned with complexes of proteins termed “Exomyc complexes” ([0001]). Ramos teaches that the polyproteins contain immunogenic regions (i.e., vaccine antigens) derived from antigens P36, P46, HSP, NrdF, P97, MHP271 and P216 of M. hyopneumoniae (i.e., pathogenic antigens), such that the regions are fused to segments of the exosome carrier proteins Rrp4, Rrp41 and Rrp42 of Pyrococcus abyssi (i.e., exosome marker proteins) ([0011]). Ramos teaches the use of a gene (i.e., a nucleic acid construct) or plasmid encoding the nucleotide sequences of segments of the exosomes (i.e., a first nucleic acid sequence encoding an exosome marker protein) and the immunogenic regions (i.e. a second nucleic acid sequence encoding a vaccine antigen) such that the exosomes and immunogenic regions are expressed in a fused form and are present within exosomes ([0016], [0026]; see Fig. 9).
Ramos discloses each and every limitation of claims 17, 22-25, 30-31, and 36, and therefore Ramos anticipates claims 17, 22-25, 30-31, and 36.
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 18-21, 26-29, and 32-35 are rejected under 35 U.S.C. 103 as being unpatentable over Ramos (PG Pub No. US 2017/0274062 A1, filed 8 May 2015) in view of Seow (US Patent No. 10,233,445 B2, filed 8 September 2015), as evidenced by Maecker (BMC immunology 4.1 (2003): 1-14).
Regarding claims 18-21, 26-29, and 32-35, Ramos anticipates claims 17, 22-25, 30-31, and 36 as described above.
Ramos does not teach or suggest that the exosome marker protein is a protein that is present within a membrane of an exosome (Claims 18, 26, and 32). Ramos does not teach or suggest that the exosome marker protein belongs to the tetraspanin family (Claims 19, 27, and 33). Ramos does not teach or suggest that the exosome marker protein is CD81 (Claims 20-21, 28-29, and 34-35).
However, one of ordinary skill in the art would have considered the teachings of Seow and Maecker both references are analogous prior art pertaining to the study and use of exosomes.
Seow is drawn to an invention concerned with exosomes utilized for the delivery of genetic material (Abstract). Seow teaches the use of nucleic acid constructs that encode exosomes having a targeting moiety expressed on their surface (Col. 2, lines 49-58). Seow teaches that the exosomes of the disclose comprise exosome transmembrane proteins (i.e., exosome marker proteins present in a membrane of an exosome) that include CD81 and tetraspanins (Col. 8, lines 17-36).
Maecker is drawn to a study concerned with CD81 and teaches that CD81 directly enhances Th1 cell activation (pg. 1; see “Results”). Maecker teaches that CD81 is part of the tetraspanin superfamily (pg. 1; see “Abstract”).
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 nucleic acid encoding an exosome, as described by Ramos, with a nucleic acid encoding an exosome comprising a CD81 exosome marker protein within its membrane that is capable of inducing a Th1-type immune response, as described and evidenced by Seow and Maecker. A person of ordinary skill in the art would have had a reasonable expectation of success because simple substitution of one known element for another is known in the art. Therefore, substituting the nucleic acid encoding an exosome, as described by Ramos, for a nucleic acid encoding an exosome comprising CD81, as described and evidenced by Seow and Maecker, would have resulted in the predicable outcome of utilizing a transmembrane CD81 exosome marker protein that induces a Th1-type immune response within the “exomyc complex” of Ramos.
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 17-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 17/587,925.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claims 1-7 anticipate instant claims 17-36.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claims 17, 24-26, and 31, copending claim 1 recites a method of enhancing an immune response in a subject, comprising administering to the subject an effective amount of a composition that comprises at least one of: (a) a nucleic acid construct comprising a first nucleic acid sequence encoding an exosome marker protein and a second nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form; (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein so that the fused protein is present in an exosome; and (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
Therefore, the claims are not deemed to be patentably distinct.
Regarding instant claims 18 and 32, copending claim 2 recites that the exosome marker protein is present in the membrane of an exosome.
Regarding instant claims 19, 27, and 33, copending claim 3 recites that the exosome marker protein belongs to the tetraspanin family.
Regarding instant claims 20, 28, and 24, copending claim 4 recites that the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.
Regarding instant claims 21, 29, and 35, copending claim 5 recites that the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
Regarding instant claims 22, 30, and 36, copending claim 6 recites that the antigen is selected from a cancer antigen and a viral antigen.
Regarding instant claim 23, copending claim 7 recites that the nucleic acid construct is a plasmid DNA.
Claims 17-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11, 21-23, and 25-27 of copending Application No. 16/091,073.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claims 11, 21-23, and 25-27 anticipate instant claims 17-36.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claims 17, 25, and 31, copending claim 11 recites a protein in a form of a vaccine antigen protein fused with an exosome marker protein.
Therefore, the claims are not deemed to be patentably distinct.
Regarding instant claims 18, 24, and 32, copending claims 21-22 recite that the exosome marker protein is a protein that is present in a membrane of an exosome.
Regarding instant claims 19, 27, and 33, copending claim 23 recites that the exosome marker protein belongs to the tetraspanin family.
Regarding instant claims 20-21, 28-29, and 34-35, copending claim 25 recites that the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
Regarding instant claims 22, 30, and 36, copending claim 26 recites that the antigen is a viral antigen.
Regarding instant claims 23, 26, and 32, copending claim 27 recites that the vaccine DNA (i.e., the nucleic acid construct) is plasmid DNA.
Conclusion

APPLICANT REBUTTAL: Reply to Office Action dated July 29, 2024
REMARKS
Applicant respectfully requests reconsideration of this application in view of the above amendments and the following remarks. Claims 17-36 are pending.
Rej
ections Under 35 U.S.C.
Q
Claims 17, 22-25, 30, 31, and 36 are rejected under 35 U.S.C. § 102 as anticipated by Ramos (U.S. Publication No. 2017/0274062, D1).
Applicant respectfully traverses this rejection. The term "exosome" recited in the instant claims is different from the exosome complex disclosed in D1. In the present application, this term refers to
extracellular
microparticle, which is a membrane vesicle secreted from a cell (see e.g., paragraphs [0008] and [0025] of the present application). The "exosome complex" disclosed in D1 is a protein complex consisting of three copies of three different proteins (see paragraph [0107] of D1). D1 further cites Navarro M V et al., J Biol Chem. 283: 14120-31, 2008 as disclosing that the structural characterization of the complex. Id. Navarro (enclosed) describes exosome complex plays a central role related to RNA processing and degradation both in the
nucleus
and in the
cytoplasm
(see left column on page 14120). See also Belostotsk, Current Opinion in Cell Biology 21: 352-8, 2009 (enclosed) (see 1st sentence in Abstract); Evguenieva-Hackenberg and Klug, Progress in Molecular Biology and Translational Science 85: 275-317, 2009 (see e.g., Fig. 4 on page 304). Thus, the exosome of the present application is different from the exosome complex of D1. Further support for the terms "exosome" and "exosome complex" being different may be found, for example, in van Niel et al., Nature Reviews 19:213-228, 2018 (enclosed) (see 1st sentence in paragraph bridging left and right columns on page 213, stating "[t]he term exosome (which should not be confused with the exosome complex, which is involved in RNA degradation)...") (emphasis added). Accordingly, D1 fails to disclose a fusion protein that comprises a vaccine antigen and an exosome marker protein or a nucleic acid construct encoding such a fusion protein.
In view of the above remarks, Applicant submits that this rejection has been overcome. Withdrawal of this rejection is respectfully requested.
Reply to Office Action dated July 29, 2024
Rej
ections Under 35 U.S.C.
Q
Claims 18-21, 26-29, and 32-35 are rejected under 35 U.S.C. § 103 as unpatentable over Ramos (U.S. Publication No. 2017/0274062, D1) in view of Seow (U.S. Patent No. 10,233,445, D2) as evidenced by Maecker et al. (BMC Immunology 4.1:1-14, 2003, D3).
Applicant respectfully traverses this rejection. As discussed above, D1 fails to disclose a fusion protein that comprises a vaccine antigen and an exosome marker protein or a nucleic acid construct encoding such a fusion protein. Such a deficiency has not been remedied by either D2 or D3. D2 is cited in the Office Action as relating to using exosomes for delivering genetic materials. D3 is cited in the Office Action as using CD81, a member of the tetraspanin superfamily, to enhance Th1 cell activation.
In view of the above remarks, Applicant submits that this rejection has been overcome. Withdrawal of this rejection is respectfully requested.
Double Patenting
Claims 17-37 are provisionally rejected on the ground of nonstatutory double patenting as unpatentable over claims 1-7 of copending Application No. 17/587,925.
Claims 17-36 are provisionally rejected on the ground of nonstatutory double patenting as unpatentable over claims 11, 21-23, and 25-27 of copending Application No. 16/091,073.
Application No. 18/448,713 Reply to Office Action dated July 29, 2024
Applicant will file a terminal disclaimer or otherwise overcome these provisional
rejections once the present application or the copending applications become otherwise
allowable.
Respectfully submitted,

NEXT OFFICE 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 .
Application Status
This action is written in response to applicant’s correspondence received 20 September 2024. Claims 17-36 are pending. Claims 1-16 are canceled. Accordingly, claims 17-36 are currently under examination.
Any objection or rejection of record in the previous Office Action, mailed 29 July 2024, which is not addressed in this action has been withdrawn in light of applicant’s amendments and/or arguments. This action is FINAL.
Withdrawn Claim Rejections
Applicant’s arguments and amendments, filed 20 September 2024, have been fully considered and are deemed persuasive. Accordingly, the previous USC § 102 and 103 rejections of record are withdrawn.
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 17-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 17/587,925. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claims 1-7 anticipate instant claims 17-36.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claims 17, 24-26, and 31, copending claim 1 recites a method of enhancing an immune response in a subject, comprising administering to the subject an effective amount of a composition that comprises at least one of: (a) a nucleic acid construct comprising a first nucleic acid sequence encoding an exosome marker protein and a second nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form; (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein so that the fused protein is present in an exosome; and (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
Therefore, the claims are not deemed to be patentably distinct.
Regarding instant claims 18 and 32, copending claim 2 recites that the exosome marker protein is present in the membrane of an exosome.
Regarding instant claims 19, 27, and 33, copending claim 3 recites that the exosome marker protein belongs to the tetraspanin family.
Regarding instant claims 20, 28, and 24, copending claim 4 recites that the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.
Regarding instant claims 21, 29, and 35, copending claim 5 recites that the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
Regarding instant claims 22, 30, and 36, copending claim 6 recites that the antigen is selected from a cancer antigen and a viral antigen.
Regarding instant claim 23, copending claim 7 recites that the nucleic acid construct is a plasmid DNA.
Claims 17-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11, 21-23, and 25-27 of copending Application No. 16/091,073. This rejection is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claims 11, 21-23, and 25-27 anticipate instant claims 17-36.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claims 17, 25, and 31, copending claim 11 recites a protein in a form of a vaccine antigen protein fused with an exosome marker protein.
Therefore, the claims are not deemed to be patentably distinct.
Regarding instant claims 18, 24, and 32, copending claims 21-22 recite that the exosome marker protein is a protein that is present in a membrane of an exosome.
Regarding instant claims 19, 27, and 33, copending claim 23 recites that the exosome marker protein belongs to the tetraspanin family.
Regarding instant claims 20-21, 28-29, and 34-35, copending claim 25 recites that the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
Regarding instant claims 22, 30, and 36, copending claim 26 recites that the antigen is a viral antigen.
Regarding instant claims 23, 26, and 32, copending claim 27 recites that the vaccine DNA (i.e., the nucleic acid construct) is plasmid DNA.
Response to Arguments
Applicant’s arguments, field 20 September 2024, have been fully considered and are deemed persuasive. Accordingly, the previous 35 USC § 102 and 103 rejections of record, filed 29 July 2024, have been withdrawn.
Insofar as Applicant’s arguments are applicable to the currently pending nonstatutory double patenting rejections of record, Applicant may file a terminal disclaimer over copending Application No. 17/587,925 and 16/091,073 in order to overcome the currently pending nonstatutory double patenting rejections of record.
Conclusion
THIS ACTION IS MADE FINAL.  Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action.  In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action.  In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.

CITED REFERENCE SUMMARIES: Ref US20170274062A1: Claims:
A complex of immunogenic polyproteins of M. hyopneumoniae comprising immunogenic and stable segments derived from P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae, fused to segments of P. abyssi exosome, wherein the major segments of amino acids derived from M. hyopneumoniae antigens are directly linked to proteins of said P. abyssi exosome, while smaller segments are at the C-terminal extreme of the fusions.
A complex of immunogenic polyproteins according to claim 1 , wherein the proteins of P. abyssi exosome selected for fusion with the immunogenic and stable segments derived from P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae are Rrp4, Rrp41 and Rrp42, wherein the stability of the complex is reached by interaction of said proteins, thus maintaining all antigens in a single proteic complex.
A complex of immunogenic polyproteins of M. hyopneumoniae according to claim 1 , comprising an amino acids sequence selected from: (a) SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28; (b) conservatively modified variants having at least 85% of identity in relation to amino acids sequences of the sequences SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28, and having substantially the same immunogenic activity thereof; (c) fragments of sequences SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28, said fragments comprising immunogenic and stable regions of P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens; and (d) a fusion protein encoded by nucleotide sequence of SEQ ID NO: 25, a conservatively modified variant of said fusion protein or a fragment of said fusion protein having the same immunogenic activity.
(a) SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28;
(b) conservatively modified variants having at least 85% of identity in relation to amino acids sequences of the sequences SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28, and having substantially the same immunogenic activity thereof;
(c) fragments of sequences SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28, said fragments comprising immunogenic and stable regions of P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens; and
(d) a fusion protein encoded by nucleotide sequence of SEQ ID NO: 25, a conservatively modified variant of said fusion protein or a fragment of said fusion protein having the same immunogenic activity.
A complex of immunogenic polyproteins according to claim 3 , comprising the amino acids sequences of SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28.
A complex of immunogenic polyproteins according to claim 3 , comprising a fusion protein encoded by nucleotide sequence of SEQ ID NO:25.
A gene encoding a complex of immunogenic polyproteins of M. hyopneumoniae comprising nucleotide sequences encoding immunogenic and stable segments derived from P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae, and encoding nucleotide sequences of segments of P. abyssi exosome, forming a fusion protein of said immunogenic and stable segments with said segments of P. abyssi exosome so that the encoding nucleotide sequences of greater segments of amino acid derived from M. hyopneumoniae antigens are directly linked to nucleotide sequences encoding the proteins of said P. abyssi exosome, while the nucleotide sequences encoding said minor segments of amino acids derived from M. hyopneumoniae antigens are in the C-terminal extreme of the fusion protein.
A gene according to claim 6 , wherein the encoding nucleotide sequences of proteins of P. abyssi exosome selected for fusion with the immunogenic and stable segments specific of P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae are the encoding nucleotide sequences of Rrp4, Rrp41 and Rrp42 proteins of P. abyssi.
A gene encoding a complex of immunogenic polyproteins of M. hyopneumoniae according to claim 6 , comprising a nucleotide sequence selected from group consisting of: (a) SEQ ID NO:25; and (b) a nucleotide sequence having at least 75% of identity related to SEQ ID NO:25.
(a) SEQ ID NO:25; and
(b) a nucleotide sequence having at least 75% of identity related to SEQ ID NO:25.
A gene according to claim 8 , wherein said nucleotide sequence encodes the polyproteins comprising the sequences SEQ ID NO:26 SEQ ID NO:27 and SEQ ID NO:28.
A process for obtaining a complex of immunogenic polyproteins, comprising the steps of: (i) preparation of an expression system comprising: (a) a gene encoding a complex of polyproteins of M. hyopneumoniae comprising nucleotide sequences encoding immunogenic and stable segments derived from P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae and encoding nucleotide sequences of segments of P. abyssi exosome, forming a fusion protein of said immunogenic and stable segments with said segments of P. abyssi exosome so that the encoding nucleotide sequences of greater segments of amino acid derived from M. hyopneumoniae antigens are directly linked to nucleotide sequences encoding the proteins of said P. abyssi exosome, while the nucleotide sequences encoding said minor segments of amino acids derived from M. hyopneumoniae antigens are in the C-terminal extreme of the fusion protein; (b) an expression system, optionally selected from Escherichia coli strain BL21 (DE3) or Rosetta (DE3), and (c) an expression vector containing the phage promoter T7; (ii) innoculation of host cells with the expression system prepared in step (i); (iii) lysing the cells to obtain said complex of immunogenic polyproteins of M. hyopneumoniae; and (iv) purification of said complex obtained in step (iii).
(i) preparation of an expression system comprising: (a) a gene encoding a complex of polyproteins of M. hyopneumoniae comprising nucleotide sequences encoding immunogenic and stable segments derived from P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae and encoding nucleotide sequences of segments of P. abyssi exosome, forming a fusion protein of said immunogenic and stable segments with said segments of P. abyssi exosome so that the encoding nucleotide sequences of greater segments of amino acid derived from M. hyopneumoniae antigens are directly linked to nucleotide sequences encoding the proteins of said P. abyssi exosome, while the nucleotide sequences encoding said minor segments of amino acids derived from M. hyopneumoniae antigens are in the C-terminal extreme of the fusion protein; (b) an expression system, optionally selected from Escherichia coli strain BL21 (DE3) or Rosetta (DE3), and (c) an expression vector containing the phage promoter T7;
(a) a gene encoding a complex of polyproteins of M. hyopneumoniae comprising nucleotide sequences encoding immunogenic and stable segments derived from P36, P46, HSP (P42), NrdF, P97, MHP271 and P216 antigens of M. hyopneumoniae and encoding nucleotide sequences of segments of P. abyssi exosome, forming a fusion protein of said immunogenic and stable segments with said segments of P. abyssi exosome so that the encoding nucleotide sequences of greater segments of amino acid derived from M. hyopneumoniae antigens are directly linked to nucleotide sequences encoding the proteins of said P. abyssi exosome, while the nucleotide sequences encoding said minor segments of amino acids derived from M. hyopneumoniae antigens are in the C-terminal extreme of the fusion protein;
(b) an expression system, optionally selected from Escherichia coli strain BL21 (DE3) or Rosetta (DE3), and
(c) an expression vector containing the phage promoter T7;
(ii) innoculation of host cells with the expression system prepared in step (i);
(iii) lysing the cells to obtain said complex of immunogenic polyproteins of M. hyopneumoniae; and
(iv) purification of said complex obtained in step (iii).
The process according to claim 10 , wherein the encoding gene of step (i) (a) is formed by DNA amplification of primer sequences: SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO: 31 , SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35 and SEQ ID NO:36.
The process according to claim 10 , wherein said expression vector containing the phage promoter T7 of step (i) (c) is selected from the group consisting of plasmid of pET series and the pMRK plasmid.
The process according to claim 12 , wherein said plasmid of pET series is pRSET.
The process according to claim 12 , wherein said plasmid is pMRK.
An antigenic composition, comprising: (a) complex of immunogenic polyproteins of M. hyopneumoniae of claim 1 ; (b) optionally, an adjuvant; and (c) a pharmaceutically acceptable vehicle.
(a) complex of immunogenic polyproteins of M. hyopneumoniae of claim 1 ;
(b) optionally, an adjuvant; and
(c) a pharmaceutically acceptable vehicle.
The antigenic composition according to claim 15 , wherein said adjuvant is selected from group consisting of: incomplete Freund's adjuvant, the complete Freund's adjuvant, polydisperse acetylated mannan Î²-(1,4) linked, adjuvants of copolymer of polyoxiethylene-polyoxipropylene, modified lipid adjuvants, adjuvants derived from saponine, dextran sulfate, aluminum hydroxide and aluminum phosphate.
The antigenic composition according to claim 15 , wherein said pharmaceutically acceptable vehicle includes preservatives, diluents, emulsifiers, stabilizers and other pharmaceutically acceptable ingredients.
A method of treatment of infection caused by Mycoplasma hyopneumoniae, the method comprising administration of the complex of immunogenic polyproteins of M. hyopneumoniae as defined in claim 1 to a patient in need of treatment.
A method of prophylaxis of infections caused by Mycoplasma hyopneumoniae, the method comprising administration of the complex of immunogenic polyproteins of M. hyopneumoniae as defined in claim 1 to a patient in need of prophylaxis.
The process of claim 10 , wherein the gene encoding a of complex of polyproteins comprises the sequences SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28.
Ref US10233445B2: Claims:
What is claimed is: 1. A method of targeting an exosome to a selected tissue or cell type, comprising expressing a targeting moiety as a fusion protein between the targeting moiety and an exosomal transmembrane protein on the surface of the exosome, wherein the targeting moiety is a peptide of from 5 to 100 amino acids in length, and binds a cell surface moiety expressed on the surface of the selected tissue or cell type, wherein the exosomal transmembrane protein is selected from Lamp-1, Lamp-2, CD13, Flotillin, Syntaxin-3, CD44, ICAM-1, Integrin alpha4, L1CAM, LFA-1, Vti-1A and B, CD9, CD37, CD53, CD63, CD81, CD82 and tetraspanins. 2. The method according to claim 1, wherein the targeting moiety targets the exosome to tissue or cells selected from muscle, brain, liver pancreas and/or lung. 3. The method according to claim 1, wherein the targeting moiety targets the exosome to diseased tissue or diseased cells. 4. The method according to claim 1, wherein the targeting moiety is separated from the transmembrane protein by a spacer or linker sequence. 5. The method according to claim 4, wherein the spacer or linker sequence is a peptide of from 1 to 5 amino acids. 6. The method according to claim 5, wherein the spacer or linker comprises alanine, arginine, serine and/or glycine residues. 7. The method according to claim 1, wherein the exosome is loaded with exogenous genetic material. 8. The method according to claim 3, wherein the diseased tissue is a tumour tissue, or the diseased cell is a tumour cell.
A method of targeting an exosome to a selected tissue or cell type, comprising expressing a targeting moiety as a fusion protein between the targeting moiety and an exosomal transmembrane protein on the surface of the exosome, wherein the targeting moiety is a peptide of from 5 to 100 amino acids in length, and binds a cell surface moiety expressed on the surface of the selected tissue or cell type, wherein the exosomal transmembrane protein is selected from Lamp-1, Lamp-2, CD13, Flotillin, Syntaxin-3, CD44, ICAM-1, Integrin alpha4, L1CAM, LFA-1, Vti-1A and B, CD9, CD37, CD53, CD63, CD81, CD82 and tetraspanins.
The method according to claim 1, wherein the targeting moiety targets the exosome to tissue or cells selected from muscle, brain, liver pancreas and/or lung.
The method according to claim 1, wherein the targeting moiety targets the exosome to diseased tissue or diseased cells.
The method according to claim 1, wherein the targeting moiety is separated from the transmembrane protein by a spacer or linker sequence.
The method according to claim 4, wherein the spacer or linker sequence is a peptide of from 1 to 5 amino acids.
The method according to claim 5, wherein the spacer or linker comprises alanine, arginine, serine and/or glycine residues.
The method according to claim 1, wherein the exosome is loaded with exogenous genetic material.
The method according to claim 3, wherein the diseased tissue is a tumour tissue, or the diseased cell is a tumour cell.
Ref APP-17_587925: Claims:
A method of enhancing an immune response in a subject, comprising administering to the subject an effective amount of a composition that comprises at least one selected from the group of: (a) a nucleic acid construct comprising a first nucleic acid sequence encoding an exosome marker protein and a second nucleic acid sequence encoding a vaccine antigen, wherein the exosome marker protein and the vaccine antigen are expressed in a fused form; (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein so that the fused protein is present in an exosome; and (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form, wherein the exosome is an extracellular membrane vesicle.
The method of claim 1, wherein the exosome marker protein is a protein that is present in a membrane of an exosome.
The method of claim 1, wherein the exosome marker protein belongs to the tetraspanin family.
The method of claim 1, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.
The method of claim 1, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
The method of claim 1, wherein the antigen is selected from a cancer antigen and a viral antigen.
The method of claim 1, wherein the nucleic acid construct is a plasmid DNA.
The method of claim 1, wherein the immune response is Th1-type immunity induction.
The method of claim 1, wherein the composition comprises (a) the nucleic acid construct comprising the first nucleic acid sequence encoding the exosome marker protein and the second nucleic acid sequence encoding a vaccine antigen.
The method of claim 1, wherein the composition comprises (b) the protein in the form of the vaccine antigen protein fused with the exosome marker protein.
The method of claim 1, wherein the composition comprises (c) the exosome comprising the vaccine antigen protein and the exosome marker protein in the fused form.
Ref APP-16_091073: Claims:
A nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen.
The nucleic acid construct of claim 1, wherein the exosome marker protein is a protein that is present in a membrane of an exosome.
The nucleic acid construct of claim 1, wherein the exosome marker protein belongs to the tetraspanin family.
The nucleic acid construct of claim 1, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.
The nucleic acid construct of claim 1, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
The nucleic acid construct of claim 1, wherein the antigen is selected from a cancer antigen and a viral antigen.
The nucleic acid construct of claim 1, which is a plasmid DNA.
A DNA vaccine comprising the nucleic acid construct of claim 1.
The DNA vaccine of claim 8 for improving Th1-type immunity induction.
The DNA vaccine of claim 9, characterized in targeting cancer or a viral disease.
A protein in a form of a vaccine antigen protein fused with an exosome marker protein.
An exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
An immune response enhancer comprising the nucleic acid construct of claim 1.
A composition for enhancing a T cell response comprising the protein of claim 11.
A cytotoxic agent comprising the exosome of claim 12.
A medicament comprising one of: (a) a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen; (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein; or (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
A medicament for treating or preventing cancer, comprising the medicament of claim 16.
A method of enhancing an immune response in a subject, comprising administering to the subject an effective amount of a composition that comprises at least one of: (a) a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen; (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein; and (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
A method of enhancing a T cell response, comprising administering to a subject an effective amount of a composition that comprises at least one of: (a) a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen: (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein; and (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
A method of treating or preventing cancer, comprising administering to a subject an effective amount of a composition that comprises at least one of: (a) a nucleic acid construct comprising a nucleic acid sequence encoding an exosome marker protein and a nucleic acid sequence encoding a vaccine antigen: (b) a protein in a form of a vaccine antigen protein fused with an exosome marker protein; and (c) an exosome comprising a vaccine antigen protein and an exosome marker protein in a fused form.
A composition for improving immunogenicity of a vaccine DNA, comprising a nucleic acid sequence encoding an exosome marker protein.
The composition of claim 21, wherein the exosome marker protein is a protein that is present in a membrane of an exosome.
The composition of claim 21, wherein the exosome marker protein belongs to the tetraspanin family.
The composition of claim 21, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, CD9, CD31, HLA-G, TSG101, Rab5b, and ALIX.
The composition of claim 21, wherein the exosome marker protein is selected from the group consisting of CD63, CD81, and CD9.
The composition of claim 21, wherein an antigen contained in the vaccine DNA is selected from a cancer antigen and a viral antigen.
The composition of claim 21, wherein the vaccine DNA is a plasmid DNA.