IP Library › Granted Patent US 12,257,313
Granted Patent B2
US 12,257,313 · App. 18/050,005 · Granted Mar 25, 2025

Preparation of therapeutic exosomes using membrane proteins

Inventors: Kevin P. Dooley (Boston, MA); Rane A. Harrison (Belmont, MA); Russell E. McConnell (Brighton, MA); Ke Xu (Sudbury, MA); Damian J. Houde (Plymouth, MA); Nikki Ross (Cambridge, MA); Sonya Haupt (Cambridge, MA); John D. Kulman (Belmont, MA); Douglas E. Williams (Boston, MA)
Assignee: LONZA SALES AG
A61K47/6917C07K14/705C07K14/70503C07K14/70596C07K14/71C07K14/755C07K16/2803C07K16/2851A61K38/00C07K2317/55C07K2317/622C07K2319/00C07K2319/30C07K2319/43C07K2319/60
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Quick Facts
Patent No.
US 12,257,313
App. No.
18/050,005
Granted
Mar 25, 2025
Kind
B2
Abstract

The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Claims (21)

1. A pharmaceutical composition comprising:

a. an exosome comprising a target protein, wherein at least a part of the target protein is expressed from an exogenous sequence, and the target protein comprises Prostaglandin F2 Receptor Negative Regulator (PTGFRN) or a fragment thereof and:

b. an excipient.

2. The pharmaceutical composition of claim 1 , wherein the target protein comprises a polypeptide of SEQ ID NO: 1.

3. The pharmaceutical composition of claim 1 , wherein the target protein comprises a polypeptide of SEQ ID NO: 33.

4. The pharmaceutical composition of claim 1 , produced from a cell genetically modified to comprise the exogenous sequence.

5. The pharmaceutical composition of claim 4 , wherein the cell is an HEK293 cell.

6. The pharmaceutical composition of claim 4 , wherein the cell comprises a plasmid comprising the exogenous sequence.

7. The pharmaceutical composition of claim 4 , wherein the cell comprises the exogenous sequence inserted into a genome of the cell.

8. The pharmaceutical composition of claim 7 , wherein the exogenous sequence is inserted into a genomic site located 3′ or 5′ end of a genomic sequence encoding PTGFRN or a fragment thereof.

9. The pharmaceutical composition of claim 7 , wherein the exogenous sequence is inserted into a genomic sequence encoding PTGFRN.

10. The pharmaceutical composition of claim 4 , wherein the cell is modified to have a reduced expression of ADAM10.

11. The pharmaceutical composition of claim 1 , wherein the target protein is a fusion protein comprising PTGFRN or a fragment thereof, and a therapeutic peptide.

12. The pharmaceutical composition of claim 11 , wherein the therapeutic peptide is selected from the group consisting of a natural peptide, a recombinant peptide, a synthetic peptide, or a linker to a therapeutic compound.

13. The pharmaceutical composition of claim 11 , wherein the therapeutic compound is selected from the group consisting of nucleotides, amino acids, lipids, carbohydrates, and small molecules.

14. The pharmaceutical composition of claim 11 , wherein the therapeutic peptide is an antibody or a fragment thereof.

15. The pharmaceutical composition of claim 11 , wherein the therapeutic peptide is an enzyme, a ligand, a receptor, or a fragment thereof.

16. The pharmaceutical composition of claim 1 , wherein the target protein is a fusion protein comprising PTGFRN or a fragment thereof, and a targeting moiety.

17. The pharmaceutical composition of claim 16 , wherein the targeting moiety is specific to an organ, a tissue, or a cell.

18. The pharmaceutical composition of claim 1 , substantially free of macromolecules, wherein the macromolecules are selected from nucleic acids, contaminant proteins, lipids, carbohydrates, metabolites, and a combination thereof.

19. The pharmaceutical composition of claim 1 , wherein the exosome further comprises a second target protein, wherein the second target protein comprises PTGFRN, BSG, IGSF3, IGSF2, ITGB1, ITGA4, SLC3A2, ATP transporter, or a fragment thereof.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2023
From: DOOLEY, KEVIN P.; HARRISON, RANE A.; MCCONNELL, RUSSELL E.; XU, KE; HOUDE, DAMIAN J.; ROSS, NIKKI; HAUPT, SONYA; KULMAN, JOHN D.; WILLIAMS, DOUGLAS E.
To: CODIAK BIOSCIENCES, INC.
Reel/Frame 064790/0294 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2023
From: CODIAK BIOSCIENCES, INC.
To: LONZA SALES AG
Reel/Frame 064251/0794 →
Continuity (6)
Division 16722884 · Dec 20, 2019
Continuation 16231012 · Dec 21, 2018
Continuation 16112547 · Aug 24, 2018
Provisional Application 62656956 · Apr 12, 2018
Provisional Application 62550543 · Aug 25, 2017
Related Publication 20240009322A1 · Jan 11, 2024
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Cited By (1)
US 12,648,907