Office Action 1: Non-Final Rejection (2024-07-10)
Rejection types: Double Patenting

CLAIMS:
Amendments to the Claims

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

1-20. (Canceled) 219

21\. (New) An exosome comprising a fusion protein which is present on an exterior surface of the exosome, wherein the fusion protein comprises (i) an immunomodulating component and (ii) a prostaglandin F2 receptor negative regulator (PTGFRN) or a functional fragment thereof, and wherein the immunomodulating component comprises a cytokine.

22\. (New) The exosome of claim 21, wherein the cytokine comprises an interleukin-12 (IL-12) protein or an interleukin-15 (IL-15) protein.

23\. (New) The exosome of claim 22, wherein the cytokine is fused to the N-terminus of the PTGFRN or functional fragment thereof.

24\. (New) The exosome of claim 21, wherein the PTGFRN comprises the full-length PTGFRN.

25\. (New) The exosome of claim 21, wherein the functional fragment of the PTGFRN comprises the region before the C-terminal-most IgV domain, the transmembrane domain, and the intracellular domain of PTGFRN.

26\. (New) The exosome of claim 22, wherein the cytokine is an IL-12 protein and the fusion comprises the amino acid sequence set forth in SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO:
5, or SEQ ID NO: 6.

27\. (New) The exosome of claim 22, wherein the cytokine is an IL-15 protein and the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 16.

28\. (New) The exosome of claim 26, wherein the PTGFRN or functional fragment thereof comprises: (i) amino acid residues 561-1,418 of SEQ ID NO: 3; (ii) 564-1,421 of SEQ ID NO: 4; (iii) amino acid residues 561-753 of SEQ ID NO: 5; or (iv) amino acid residues 563-756 of SEQ ID NO: 6.

29\. (New) The exosome of claim 27, wherein the PTGFRN or functional fragment thereof comprises: (i) amino acid residues 561-1,418 of SEQ ID NO: 3; (ii) 564-1,421 of SEQ ID NO: 4; (iii) amino acid residues 561-753 of SEQ ID NO: 5; or (iv) amino acid residues 563-756 of SEQ ID NO: 6

30\. (New) The exosome of claim 22, which comprises one or more additional immunomodulating components.
31\. (New) The exosome of claim 28, wherein the one or more additional immunomodulating components comprise (i) an inhibitor for a negative checkpoint regulator or an inhibitor for a binding partner of a negative checkpoint regulator; (ii) an activator for a positive co- stimulatory molecule or an activator for a binding partner of a positive co-stimulatory molecule;
(iii) a cytokine or a binding partner of a cytokine; (iv) a T-cell receptor (TCR), a T-cell co-receptor, a major histocompatibility complex (MHC), a human leukocyte antigen (HLA), or a derivative thereof; (v) an activator of a T-cell receptor or co-receptor; (vi) a tumor antigen; (vii) an agonist or an antagonist; (viii) an antibody or an antigen-binding fragment; (ix) a polynucleotide; (x) a protein, a peptide, a glycolipid, or a glycoprotein; or (xi) combinations thereof.
32\. (New) The exosome of claim 30, wherein the one or more additional immunomodulating components comprise a CD40L, a FLT3L, or both.

33\. (New) The exosome of claim 32, wherein (a) the CD40L is present on the exterior surface of the exosome as a fusion protein, (b) the FLT3L is present on the exterior surface of the exosome as a fusion protein, or (c) both (a) and (b).

34\. (New) The exosome of claim 33, wherein the fusion protein comprising the CD40L comprises the amino acid sequence set forth in SEQ ID NO: 19 or SEQ ID NO: 20.

35\. (New) The exosome of claim 33, wherein the fusion protein comprising the FLT3L comprises the amino acid sequence set forth in SEQ ID NO: 22.

36\. (New) A composition comprising the exosome of claim 21, and a pharmaceutically- acceptable carrier.

37\. (New) A composition comprising the exosome of claim 22, and a pharmaceutically acceptable carrier.

38\. (New) A composition comprising the exosome of claim 26, and a pharmaceutically acceptable carrier.

39\. (New) A composition comprising the exosome of claim 27, and a pharmaceutically acceptable carrier.

40\. (New) A composition comprising the exosome of claim 30, and a pharmaceutically acceptable carrier.
Atty. Dkt. No. 4000.0180005/C-K/DKC Atty. Dkt. No. 4000.0180005/C-K/DKC

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 .
The preliminary amendments of 01/06/2023 have been entered in full. Claims 21-40 are pending and under consideration.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 21-24, 30, 32, 33, 36, 37, and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 10-17 of U.S. Patent No. 12030924. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims encompass overlapping subject matter as follows.
Both sets of claims encompass an exosome comprising a fusion protein, wherein the fusion protein comprises (i) an immunomodulating component and (ii) a prostaglandin F2 receptor negative regulator (PTGFRN) or a functional fragment thereof (patented claims 1 and 4, pending claim 21). Both sets encompass embodiments comprising more than one immunomodulating component (patented claims 5-7, 10-12). Both sets encompass embodiments wherein the fusion protein is present on the exterior surface of the microsome (patented claim 7, pending claims 21 and 33). In both sets, the immunomodulating component may be IL-15 (patented claim 3, pending claim 22). Both sets encompass embodiments wherein an immunomodulating component may be an activator for a positive co- stimulatory molecule or an activator for a binding partner of a positive co-stimulatory molecule (patented claim 2, pending claims 32 and 33). Pending claims 36, 37, and 40 recite that the composition comprising the claimed exosome comprises a pharmaceutically acceptable carrier, which is both implicit and obvious in view of patented claims 13-17, which recite methods of treating disease comprising administering the claimed exosome.
Claims 21, 22, 24, 25, 36, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5-7, 9, 10, 17, and 18 of U.S. Patent No. 10723782. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims encompass overlapping subject matter as follows.
Both sets of claims encompass an exosome comprising a fusion protein, wherein the fusion protein comprises (i) an immunomodulating component and (ii) a prostaglandin F2 receptor negative regulator (PTGFRN) or a functional fragment thereof, wherein the an immunomodulating component comprises a cytokine (patented claims 1,2, and 7, pending claim 21). In both sets, the immunomodulating component may be IL-15 (patented claims 5 and 6, pending claim 22). Both sets encompass embodiments comprising full-length PTGFRN or a functional fragment comprising the region before the C-terminal-most IgV domain, the transmembrane domain, and the intracellular domain of PTGFRN (patented claims 17 and 18, pending claims 24 and 25). Both sets of claims encompass a composition comprising the claimed exosome of and a pharmaceutically- acceptable carrier (patented claim 9, pending claims 36 and 37).
Conclusion
Claims 21-25, 30, 32, 33, 36, 37, and 40 are rejected.
Claims 26-29, 31, 34, 35, and 39 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.

APPLICANT REBUTTAL: REMARKS
Reconsideration of this Application is respectfully requested. Claims 21-40 are pending in the application. No new amendments are made; the listing of claims is included for convenience.
Based on the following remarks, Applicant respectfully requests that the Examiner reconsider all outstanding objections and rejections and that they be withdrawn.
Rejection of claims 21-25, 30, 32, 33, 36, 37, and 40 due to alleged nonstatutory double patenting
The Office rejects claims 21-24, 30, 32, 33, 36, 37 and 40 due to alleged nonstatutory double patenting over claims 1-8 and 10-17 of U.S. Patent No. 12,030,924. The Office also rejected claims 21, 22, 24, 25, 36, and 37 over claims 1, 2, 5-7, 9, 10, 17, and 18 of U.S. Patent No. 10,723,782.
Solely to advance prosecution of this application to allowance and without acquiescence to the double patenting rejections, Applicant files along with this reply a terminal disclaimer over the cited patents. In view of this terminal disclaimer, the Applicant respectfully requests withdrawal of the double patenting rejections.
CONCLUSION

NEXT OFFICE ACTION: DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 21-40 are pending.
Terminal Disclaimer
The terminal disclaimer filed on 10/09/2024 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Patent Nos. 10723782 and 12030924 has been reviewed and is accepted.  The terminal disclaimer has been recorded.
The following is an examiner’s statement of reasons for allowance: The approved terminal disclaimer noted above is effective to overcome the rejections previously applied.  Rejections and/or objections not reiterated from previous Office actions are hereby withdrawn.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”

CITED REFERENCE SUMMARIES: Ref US12030924: Claims:
1. A composition comprising:
an extracellular vesicle comprising a fusion protein comprising a prostaglandin F2 receptor negative regulator (PTGFRN) or a fragment thereof sharing at least 90% sequence identity with either SEQ ID NO. 1 or SEQ ID NO. 2, fused to an immunomodulating component.
2. The composition of claim 1, wherein the immunomodulating component is (i) an inhibitor for a negative checkpoint regulator or an inhibitor for a binding partner of a negative checkpoint regulator; (ii) an activator for a positive co-stimulatory molecule or an activator for a binding partner of a positive co-stimulatory molecule; (iii) a cytokine or a binding partner of a cytokine; (iv) a T-cell receptor (TCR), a T-cell co-receptor, a major histocompatibility complex (MHC), a human leukocyte antigen (HLA), or a derivative thereof; (v) an activator of a T-cell receptor or co-receptor; (vi) a tumor antigen; (vii) an agonist or an antagonist; (viii) an antibody or an antigen-binding fragment; (ix) a polynucleotide; (x) a peptide, a glycolipid, or a glycoprotein; or (xi) combinations thereof.
3. The composition of claim 2, wherein the cytokine or a binding partner of a cytokine is selected from the group consisting of IL-2, IL-7, IL-10, IL-12 and IL-15.
4. The composition of claim 1, wherein the extracellular vesicle is an exosome.
5. The composition of claim 1, wherein the extracellular vesicle comprises a second immunomodulating component.
6. The composition of claim 5, wherein the second immunomodulating component is (i) an inhibitor for a negative checkpoint regulator or an inhibitor for a binding partner of a negative checkpoint regulator; (ii) an activator for a positive co-stimulatory molecule or an activator for a binding partner of a positive co-stimulatory molecule; (iii) a cytokine or a binding partner of a cytokine; (iv) a T-cell receptor (TCR), a T-cell co-receptor, a major histocompatibility complex (MHC), a human leukocyte antigen (HLA), or a derivative thereof (v) an activator of a T-cell receptor or co-receptor; (vi) a tumor antigen; (vii) an agonist or an antagonist; (viii) an antibody or an antigen-binding fragment; (ix) a polynucleotide; (x) a peptide, a glycolipid, or a glycoprotein; or (xi) combinations thereof.
7. The composition of claim 5, wherein the second immunomodulating component is a cytokine expressed as a fusion protein displayed on a surface of the extracellular vesicle.
8. The composition of claim 7, wherein the cytokine expressed as a fusion protein comprises a tetraspanin, EWI protein/immunoglobulin superfamily member, integrin, ATP transporter protein, SLC3A2, BSG, CD98hc, or a fragment or variant thereof.
9. The composition of claim 8, wherein (i) the tetraspanin comprises CD63, CD81, CD9, or combinations thereof; (ii) the EWI protein/immunoglobulin superfamily member comprises PTGFRN, IGSF8, IGSF3, or combinations thereof (iii) the integrin comprises ITGB1, ITGA4, or both; or (iv) the ATP transporter protein comprises ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B3, ATP2B1, ATP2B2, ATP2B3, ATP2B4, or combinations thereof.
10. The composition of claim 5, wherein the second immunomodulating component is different from the first immunomodulating component.
11. The composition of claim 5, wherein the extracellular vesicle comprises a third immunomodulating component.
12. The composition of claim 11, wherein the third immunomodulating component is different from the first immunomodulating component and/or the second immunomodulating component.
13. A method of treating a disease in a subject in need thereof, comprising administering to the subject the composition of claim 1.
14. The method of claim 13, wherein the disease is a cancer.
15. A method of treating a graft-versus-host disease (GvHD) in a subject in need thereof, comprising administering to the subject the composition of claim 1.
16. A method of treating an autoimmune disease in a subject in need thereof, comprising administering to the subject the composition of claim 1.
17. A method of up-regulating or down-regulating an immune response in a subject in need thereof, comprising administering to the subject the composition of claim 1.
18. A method of producing an extracellular vesicle comprising:
(a) prostaglandin F2 receptor negative regulator (PTGFRN) or a fragment thereof sharing at least 90% sequence identity with either SEQ ID NO. 1 or SEQ ID NO. 2 fused to a cytokine,
(b) a second immunomodulating component, and/or
(c) a third immunomodulating component;
the method comprising:
(i) modifying a producer cell with the first cytokine, second, and/or third immunomodulating component wherein the first cytokine comprises IL-2, IL-7, IL-10,
IL-12, or IL-15 and
(ii) obtaining the extracellular vesicle from the producer cell.
Ref US10723782: Claims:
1. A composition comprising:
an extracellular vesicle comprising a cell membrane bounding an enclosed volume, wherein the extracellular vesicle comprises a fusion protein comprising a prostaglandin F2 receptor negative regulator (PTGFRN) or a fragment thereof fused to an immunomodulating component.
2. The composition of claim 1, wherein the immunomodulating component comprises a cytokine.
3. The composition of claim 2, wherein the cytokine is IL-7.
4. The composition of claim 2, wherein the cytokine is IL-12.
5. The composition of claim 2, wherein the cytokine is IL-15.
6. The composition of claim 2, wherein the cytokine is IL-2, IL-7, IL-10, IL-12, or IL-15.
7. The composition of claim 1, wherein the extracellular vesicle is an exosome.
8. The composition of claim 1, wherein the extracellular vesicle is a nanovesicle.
9. The composition of claim 1, further comprising a pharmaceutically-acceptable carrier.
10. The composition of claim 1, wherein the immunomodulating component is an activator for a positive co-stimulatory molecule or an activator for a binding partner of a positive co-stimulatory molecule.
11. The composition of claim 10, wherein the immunomodulating component comprises a TNF receptor superfamily member.
12. The composition of claim 11, wherein the TNF receptor superfamily member comprises CD120a, CD120b, CD18, OX40, CD40, Fas receptor, M68, CD27, CD30, 4-1BB, TRAILR1, TRAILR2, TRAILR3, TRAILR4, RANK, OCIF, TWEAK receptor, TACI, BAFF receptor, ATAR, CD271, CD269, GITR, TROY, CD358, TRAMP, or XEDAR.
13. The composition of claim 1, wherein the immunomodulating component comprises a TNF superfamily member.
14. The composition of claim 13, wherein the TNF superfamily member comprises TNFα, TNF-C, OX40L, CD40L, FasL, LIGHT, TL1A, CD27L, Siva, CD153, 4-1BB ligand, TRAIL, RANKL, TWEAK, APRIL, BAFF, CAMLG, NGF, BDNF, NT-3, NT-4, GITR ligand, or EDA-2.
15. The composition of claim 14, wherein the TNF superfamily member is CD40L.
16. The composition of claim 1, wherein the immunomodulating component comprises IFNγ.
17. The composition of claim 1, wherein the fragment of the PTGFRN comprises the region before the C-terminal-most IgV domain, the transmembrane domain, and the intracellular domain of PTGFRN.
18. The composition of claim 1, wherein the PTGFRN comprises the full-length PTGFRN.
19. The composition of claim 1, wherein the immunomodulating component comprises an inhibitor of cytotoxic T-lymphocyte-associate protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), lymphocyte-activated gene 3 (LAG3), T-cell immunoglobulin mucin-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), T cell immunoreceptor with Ig and ITIM domains (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), adenosine A2a receptor (A2aR), killer cell immunoglobulin like receptor (KIR), indoleamine 2,3-dioxygenase (IDO), CD20, CD39, or CD73.