IP Library › Granted Patent US 12,331,100
Granted Patent B2
US 12,331,100 · App. 18/049,999 · Granted Jun 17, 2025

Exosomes for immuno-oncology and anti-inflammatory therapy

Inventors: Nuruddeen D. Lewis (Andover, MA); Yu Zhou (Somerville, MA); Sriram Sathyanarayanan (Lexington, MA); John Kulman (Belmont, MA); Douglas E. Williams (Boston, MA); Leonid A. Gaydukov (Tewksbury, MA); Ke Xu (Belmont, MA); Shelly Martin (Stoneham, MA)
Assignee: LONZA SALES AG
C07K14/7151C07K14/4703C07K14/475C07K14/52C07K14/5418C07K14/5434C07K14/5443C07K14/57C07K14/70532C07K14/70575C07K14/70578C07K14/7155C07K16/2809C07K16/2818A61K2039/505A61K2039/6018A61K2039/627C07K2317/622C07K2317/76C07K2319/00C07K2319/02C07K2319/03C07K2319/31C07K2319/60
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Quick Facts
Patent No.
US 12,331,100
App. No.
18/049,999
Granted
Jun 17, 2025
Kind
B2
Abstract

Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Claims (20)

1. 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.

2. The exosome of claim 1 , wherein the PTGFRN comprises the full-length PTGFRN.

3. The exosome of claim 1 , 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.

4. A composition comprising the exosome of claim 1 , and a pharmaceutically acceptable carrier.

5. The exosome of claim 1 , wherein the cytokine comprises an interleukin-12 (IL-12) protein or an interleukin-15 (IL-15) protein.

6. The exosome of claim 5 , wherein the cytokine is fused to the N-terminus of the PTGFRN or functional fragment thereof.

7. The exosome of claim 5 , 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.

8. The exosome of claim 7 , 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.

9. The exosome of claim 8 , 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 costimulatory 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.

10. A composition comprising the exosome of claim 7 , and a pharmaceutically acceptable carrier.

11. The exosome of claim 5 , 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.

12. The exosome of claim 11 , 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.

13. A composition comprising the exosome of claim 11 , and a pharmaceutically acceptable carrier.

14. The exosome of claim 5 , which comprises one or more additional immunomodulating components.

15. The exosome of claim 14 , wherein the one or more additional immunomodulating components comprise a CD40L, a FLT3L, or both.

16. The exosome of claim 15 , 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).

17. The exosome of claim 16 , wherein the fusion protein comprising the CD40L comprises the amino acid sequence set forth in SEQ ID NO: 19 or SEQ ID NO: 20.

18. The exosome of claim 16 , wherein the fusion protein comprising the FLT3L comprises the amino acid sequence set forth in SEQ ID NO: 22.

19. A composition comprising the exosome of claim 14 , and a pharmaceutically acceptable carrier.

20. A composition comprising the exosome of claim 5 , and a pharmaceutically acceptable carrier.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 23, 2023
From: LEWIS, NURUDDEEN D.; ZHOU, YU; SATHYANARAYANAN, SRIRAM; KULMAN, JOHN D.; WILLIAMS, DOUGLAS E.; GAYDUKOV, LEONID A.; XU, KE; MARTIN, SHELLY
To: CODIAK BIOSCIENCES, INC.
Reel/Frame 064684/0437 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2023
From: CODIAK BIOSCIENCES, INC.
To: LONZA SALES AG
Reel/Frame 064251/0794 →
Continuity (5)
Division 16921351 · Jul 6, 2020
Continuation 16236246 · Dec 28, 2018
Provisional Application 62723267 · Aug 27, 2018
Provisional Application 62611140 · Dec 28, 2017
Related Publication 20240010705A1 · Jan 11, 2024
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