Office Action 2: Final Rejection (2024-11-22)
Rejection types: Double Patenting

CLAIMS:
LISTING OF THE CLAIMS

Although no amendments are made herein, the following listing of the claims is provided for the Examiner's convenience.

Listing of Claims:

1.-16. (Canceled)215

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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: 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 21 January 2025. Claims 17-36 are pending. Accordingly, claims 17-36 are currently under examination.
Withdrawn Claim Rejections
Applicant’s terminal disclaimer filed 21 January 2025 has been fully considered and is
deemed persuasive. Accordingly, the double patenting rejection of record, filed 22 November
2024, has been withdrawn.
REASONS FOR ALLOWANCE
The following is an examiner’s statement of reasons for allowance: although DNA
vaccines were developed over 20 years ago, there are still concerns surrounding the efficacy of
their immunogenicity induction. Applicant has claimed a novel and non-obvious 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 (see Claim 17).
The closest prior art, Ramos (PG Pub No. US 2017/0274062 A1), is drawn to an
invention concerned with complexes of proteins termed “Exomyc complexes” ([0001]). Ramos
teaches that the polyproteins contain immunogenic regions derived from antigens P36, P46,
HSP, NrdF, P97, MHP271 and P216 of M. hyopneumoniae, such that the regions are fused to
segments of the carrier proteins Rrp4, Rrp41 and Rrp42 of exosomes of Pyrococcus abyssi
([0011]). Ramos teaches the use of a gene or plasmid encoding the nucleotide sequences of
segments of the exosomes and the immunogenic regions such that the exosomes and
immunogenic regions are expressed in a fused form (see Claim 6).
However, Ramos does not teach or suggest that the carrier proteins are extracellular microparticles that are not degraded in the cytoplasm (Claim 17, see paragraphs [0008] and [0025]). The Exomyc complexes of Ramos is drawn to a protein complex
consisting of three copies of three different proteins that play a central role related to RNA
processing in the nuclease and cytoplasm of a cell and degrade within the cell’s cytoplasm. Accordingly, the claimed method is both novel and non-obvious in view of the closest prior art.
Conclusion

CITED REFERENCE SUMMARIES: 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.