IP Library › Granted Patent US 12,343,375
Granted Patent B2
US 12,343,375 · App. 17/650,386 · Granted Jul 1, 2025

Spray dried formulation of a cholera toxin B subunit variant

Inventors: Krystal Hamorsky (Owensboro, KY); Nobuyuki Matoba (Owensboro, KY)
Assignee: University of Louisville Research Foundation, Inc.
A61K38/164A61K9/0053A61K9/1623A61K9/1694
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Quick Facts
Patent No.
US 12,343,375
App. No.
17/650,386
Granted
Jul 1, 2025
Kind
B2
Abstract

Powder compositions and pharmaceutical compositions comprising a cholera toxin B subunit variant and a saccharide excipient are described. Methods of making the powder compositions and methods of treating a disease or enhancing wound healing using the pharmaceutical compositions are described. Liquid compositions comprising a cholera toxin B subunit variant and mannitol are described.

Claims (26)

1. A powder comprising a cholera toxin B subunit variant and mannitol, wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:3.6 and about 1:45.5.

2. The powder of claim 1 , wherein the cholera toxin B subunit variant comprises an amino acid sequence that has at least about 80% sequence identity to at least one sequence set forth in SEQ ID NOs:2, 4, 6, 8, 10, 12, 14, 16, 25-29 and 34.

3. The powder of claim 1 , wherein the cholera toxin B subunit variant comprises an endoplasmic reticulum (ER) retention sequence attached to its C-terminus.

4. The powder of claim 3 , wherein the ER retention sequence comprises SEKDEL (SEQ ID NO:30), KDEL (SEQ ID NO:31), SEHDEL (SEQ ID NO:32) or HDEL (SEQ ID NO:33).

5. The powder of claim 1 , wherein the cholera toxin B subunit variant comprises an amino acid sequence set forth in SEQ ID NO:4 or SEQ ID NO:34.

6. The powder of claim 1 , wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:3.6 and about 1:18.3.

7. The powder of claim 1 , wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:18.2 and about 1:45.5.

8. The powder of claim 1 , wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:18.2 and about 1:18.3.

9. The powder of claim 1 , further comprising KCl, KH 2 PO 4 , NaCl, and Na 2 HPO 4 .

10. The powder of claim 1 , wherein less than 10% of the cholera toxin B subunit variant is a monomer.

11. The powder of claim 1 , wherein less than 5% of the cholera toxin B subunit variant is a monomer.

12. A pharmaceutical composition comprising the powder of claim 1 , wherein the pharmaceutical composition is suitable for oral administration to a subject.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition is in a form of a capsule, and wherein the capsule comprises a polymer that degrades at about pH 6.8.

14. A powder comprising:

a) a cholera toxin B subunit variant comprising an amino acid sequence that has at least about 80% sequence identity to at least one sequence set forth in SEQ ID NOs:2, 4, 6, 8, 10, 12, 14, 16, 25-29 and 34, and

b) mannitol,

wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:3.6 and about 1:45.5.

15. The powder of claim 14 , wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:3.6 and about 1:18.3.

16. The powder of claim 14 , wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:18.2 and about 1:45.5.

17. The powder of claim 14 , wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:18.2 and about 1:18.3.

18. The powder of claim 14 , further comprising KCl, KH 2 PO 4 , NaCl, and Na 2 HPO 4 .

19. A powder comprising:

a) a cholera toxin B subunit variant comprising an amino acid sequence that has at least about 80% sequence identity to at least one sequence set forth in SEQ ID NO:4 or SEQ ID NO:34, and

b) mannitol, KCl, KH 2 PO 4 , NaCl, and Na 2 HPO 4 ,

wherein the cholera toxin B subunit variant and mannitol have a weight ratio of between about 1:3.6 and about 1:45.5.

20. A method of treating colitis, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 12 .

Assignments (2)
CONFIRMATORY LICENSE Recorded Jul 26, 2023
From: UNIVERSITY OF LOUISVILLE
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064389/0810 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 3, 2022
From: HAMORSKY, KRYSTAL; MATOBA, NOBUYUKI
To: UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION, INC.
Reel/Frame 061646/0022 →
Continuity (2)
Provisional Application 63147521 · Feb 9, 2021
Related Publication 20220249601A1 · Aug 11, 2022
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