IP Library › Granted Patent US 12708661
Granted Patent B2
US 12708661 · App. 18/261,402 · Granted Aug 18, 2026

Treatment of brain damage

Inventor: Mikhail Kalinichev (Wrexham, GB)
Assignee: Ipsen Biopharm Limited
A61K38/4893C12Y304/24069
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Quick Facts
Patent No.
US 12708661
App. No.
18/261,402
Granted
Aug 18, 2026
Kind
B2
Abstract

The present invention provides a clostridial neurotoxin for use in a method of treating a brain disorder in a patient by promoting a neuroimmune response.

Claims (20)

1 . A method for increasing microglial cell density in a patient in need thereof, the method comprising administering a clostridial neurotoxin to the patient, wherein the clostridial neurotoxin comprises botulinum neurotoxin A (BoNT/A).

2 . The method of claim 1 , wherein the clostridial neurotoxin is administered subcutaneously.

3 . The method of claim 1 , wherein the clostridial neurotoxin is administered by intracranial injection.

4 . The method of claim 1 , wherein the clostridial neurotoxin is administered at a site of brain tissue damage.

5 . The method of claim 1 , wherein the clostridial neurotoxin is administered within 4 days before brain tissue damage occurs.

6 . The method of claim 1 , wherein the clostridial neurotoxin is administered between 1-3 days before brain tissue damage occurs.

7 . The method of claim 1 , wherein the clostridial neurotoxin is administered within 24 hours following the occurrence of brain tissue damage.

8 . The method of claim 1 , wherein the clostridial neurotoxin is administered within 2 hours following the occurrence of brain tissue damage.

9 . The method of claim 1 , wherein the clostridial neurotoxin is administered within 10 minutes following the occurrence of brain tissue damage.

10 . The method of claim 4 , wherein the brain tissue damage is caused by infectious disease.

11 . The method of claim 10 , wherein the infectious disease is selected from encephalitis, meningitis, and a brain abscess.

12 . The method of claim 1 , wherein the clostridial neurotoxin is administered intrathecally or intranasally.

13 . The method of claim 1 , wherein the clostridial neurotoxin is a chimeric neurotoxin.

14 . The method of claim 1 , wherein the clostridial neurotoxin is administered in a flat dose of 100 ng.

15 . The method of claim 1 , wherein the clostridial neurotoxin is an unmodified botulinum A (BoNT/A) neurotoxin.

16 . The method of claim 1 , wherein the clostridial neurotoxin comprises a LH N domain corresponding to amino acid residues 1 to 872 of SEQ ID NO: 62.

17 . The method of claim 16 , wherein the clostridial neurotoxin comprises a H C domain corresponding to amino acid residues 860 to 1291 of SEQ ID NO: 52.

18 . The method of claim 17 , wherein the H C domain comprises an amino acid substitution selected from the group consisting of: V1118M; Y1183M; E1191M; E11911; E1191Q; E1191T; S1199Y; S1199F; S1199L; S1201V; E1191C; E1191V, E1191L; E1191Y; S1199W; S1199E; S1199H; W1178Y; W1178Q; W1178A; W1178S; Y1183C; and Y1183P.

19 . The method of claim 17 , wherein the H C domain comprises two amino acid substitutions selected from the group consisting of: E1191M and $1199L; E1191M and $1199Y; E1191M and S1199F; E1191Q and S1199L; E1191Q and S1199Y; E1191Q and S1199F; E1191M and S1199W; E1191M and W1178Q; E1191C and S1199W; E1191C and S1199Y; E1191C and W1178Q; E1191Q and S1199W; E1191V and S1199W; E1191V and $1199Y; and E1191V and W1178Q.

20 . The method of claim 1 , wherein the clostridial neurotoxin comprises a di-chain form of SEQ ID NO: 44, SEQ ID NO: 63, or SEQ ID NO: 64.