IP Library › Granted Patent US 12,622,876
Granted Patent B2
US 12,622,876 · App. 16/327,282 · Granted May 12, 2026

Methods of suppressing delivery of exosomes to liver and spleen

Inventors: Douglas E. Williams (Woburn, MA); John D. Kulman (Woburn, MA)
Assignee: LONZA SALES AG
A61K9/5068A61K9/0019A61K9/0029A61K31/713A61K48/00A61K49/0097A61K49/1896A61K51/1203C12N15/113C12N2310/14C12N2310/141C12N2320/32C12N2320/35
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Quick Facts
Patent No.
US 12,622,876
App. No.
16/327,282
Granted
May 12, 2026
Kind
B2
Abstract

The instant application describes improved methods and compositions for the systemic delivery of therapeutic exosomes to a subject in need thereof. In certain embodiments, the current invention reduces the amount of exosomes delivered to liver, spleen and combinations thereof to allow greater distribution to other areas of the body such as, but not limited to, the brain, pancreas, lung, kidney, muscle. In certain embodiments, the methods involve the injection of one or multiple doses of non-therapeutic exosomes prior to the injection of a suitable therapeutic dose of exosomes with a therapeutic payload. Also included are methods to improve immune clearance of exosomes in subjects by inhibiting phagocytosis.

Claims (29)

1 . A method of blocking the uptake of therapeutic exosomes in the liver and/or spleen of a subject, the method comprising:

intravenously administering to the subject a first dose comprising non-therapeutic exosomes;

and intravenously administering to the subject a second dose comprising therapeutic exosomes,

wherein the intravenous administration of the first dose comprising the non-therapeutic exosomes causes reduced delivery of the therapeutic exosomes to an organ selected from the group consisting of the liver, spleen, and combinations thereof, and causes increased delivery of the therapeutic exosomes to an organ selected from the group consisting of the lung, small intestine, large intestine, stomach, pancreas, and combinations thereof, compared to delivery of the therapeutic exosomes intravenously administered at the same dose, but without prior intravenous administration of the first dose comprising non-therapeutic exosomes,

wherein the second dose comprises an exosome quantity of at least about 10 10 exosomes/g by weight of the subject and the first dose is intravenously administered as a bolus dose comprising an exosome quantity that is at least 5 times greater than the second dose,

wherein the therapeutic exosomes harbor at least one therapeutic payload or have been modified to have a desired therapeutic effect as compared to non-therapeutic exosomes,

wherein the non-therapeutic exosomes do not harbor at least one therapeutic payload as compared to a therapeutic exosome, and

wherein the therapeutic and non-therapeutic exosomes are derived from a HEK293 producer cell.

2 . The method according to claim 1 , wherein the therapeutic exosomes comprise a receiver.

3 . The method of claim 1 , wherein the second dose is intravenously administered at a period of time which is 15 minutes or greater after intravenous administration of the first dose.

4 . The method of claim 1 , wherein the non-therapeutic exosomes, the therapeutic exosomes or both the non-therapeutic and therapeutic exosomes comprise an imaging agent.

5 . The method of claim 1 , wherein the therapeutic exosomes comprise:

(i) an RNA,

(ii) a DNA,

(iii) a polypeptide,

(iv) a polysaccharide,

(v) a lipid,

(vi) a toxin, or

(vii) any combination thereof.

6 . The method of claim 1 , wherein the therapeutic exosomes comprise a microRNA (miRNA), an siRNA, or an shRNA.

7 . The method of claim 1 , wherein the therapeutic exosomes comprise more than one distinct payload selected from the group consisting of: a peptide, a protein, a DNA, an siRNA, an miRNA, an shRNA, a polysaccharide, a lipid, a toxin, doxorubicin, daunorubicin, docetaxel, irinotecan, a taxane, a topoisomerase inhibitor, cyclophosphamide, a vinca alkaloid, cisplatin, a retinoid, a nucleotide analog, a kinase inhibitor, and a combination thereof.

8 . The method of claim 1 , wherein the exosomes are contacted with sialyltransferase prior to intravenous administration.

9 . A kit, comprising:

(i) a first pharmaceutical composition comprising non-therapeutic exosomes;

(ii) a second pharmaceutical composition comprising therapeutic exosomes and

(iii) instructions for use according to the method of claim 1 .

10 . The method of claim 1 , wherein the therapeutic exosomes comprise doxorubicin, daunorubicin, docetaxel, irinotecan, a taxane, a topoisomerase inhibitor, cyclophosphamide, vinca alkaloid, cisplatin, a retinoid, a nucleotide analog, a kinase inhibitor, or any combination thereof.

11 . The method of claim 1 , wherein the second dose is intravenously administered as a continuous infusion.

12 . The method of claim 1 , wherein the second dose is intravenously administered in a plurality of administration steps.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 11, 2023
From: CODIAK BIOSCIENCES, INC.
To: LONZA SALES AG
Reel/Frame 064251/0794 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2020
From: WILLIAMS, DOUGLAS E.; KULMAN, JOHN D.
To: CODIAK BIOSCIENCES, INC.
Reel/Frame 053296/0547 →
Continuity (2)
Provisional Application 62378122 · Aug 22, 2016
Related Publication 20210290556A1 · Sep 23, 2021
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