IP Library Granted Patent US 11,701,366
Granted Patent B2
US 11,701,366 · App. 17/114,335 · Granted Jul 18, 2023

Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors

Inventors: Kenneth M. Rosen (Milton, MA); Steven Wayne Riesinger (Boston, MA); Lisa McKerracher (Boston, MA); Lisa Bond Moritz (Burtonsville, MD)
Assignee: BioAxone BioSciences, Inc.
A61K31/551A61K9/0053A61K31/4545A61K31/4725A61K45/06
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Quick Facts
Patent No.
US 11,701,366
App. No.
17/114,335
Granted
Jul 18, 2023
Kind
B2
Abstract

Provided are methods of treating a cerebral cavernous malformation (CCM) and methods of treating cerebral aneurysm in a mammal with certain rho kinase inhibitors.

Claims (10)

1. A method for treating a patient having a neurological condition, the method comprising:

orally administering a pharmaceutical formulation comprising therapeutically effective amount of a rho kinase inhibitor to the patient, wherein the rho kinase inhibitor is Compound 1, having the structure:

or a pharmaceutically acceptable salt thereof, wherein administering the pharmaceutical formulation to the patient results in a reduction of one or more symptoms of the neurological condition, and

wherein the neurological condition is any of cerebral cavernous malformation, cavernous angioma, stroke, cerebral aneurysm, vasospasm, subarachnoid hemorrhage, cavernoma, a mutation in CCM1, a mutation in CCM2, a mutation in CCM3, or combinations thereof.

2. The method of claim 1 , wherein the neurological condition is cavernous angioma.

3. The method of claim 1 , wherein the symptom of the neurological condition is any of symptomatic hemorrhage, hemorrhagic stroke, epilepsy, seizures, neurological deficits, headache, previous instance of cavernous angioma, overactivation of rho signaling in endothelial cells, impaired angiogenesis, defects in vessel-like tube formations, loss of endothelial cell invasion of the extra-cellular matrix, disruption in endothelial barrier integrity, increased intracellular actin stress fibers, decreased intra-endothelial junctions, vascular leakage, increased permeability at intra-endothelial junctions, cavernoma, or combinations thereof.

4. The method of claim 1 , wherein Compound 1 is in the form of a pharmaceutically acceptable salt comprising a pharmaceutically acceptable counterion.

5. The method of claim 1 , wherein the pharmaceutical formulation further comprises a pharmaceutically acceptable carrier.

6. The method of claim 1 , wherein administering a therapeutically effective amount of a pharmaceutical formulation comprising a rho kinase inhibitor to a patient further results in an improvement of one or more conditions of the patient.

7. The method of claim 6 , wherein the condition of the patient is any of reduction in number of cerebral cavernous malformation lesions, reduction in size of CCM lesions, reduction in maturation of simple CCM lesions into clinically significant lesions, reduction in number of cerebral aneurysms, reduction in size of cerebral aneurysms, reduction in maturation of simple cerebral aneurysms into clinically significant cerebral aneurysms, reduction in size of existing saccular aneurysms, reduction in number of cavernoma, reduction in size of cavernoma, or combinations thereof.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Nov 14, 2024
From: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
To: NEURELIS, INC.; AEGIS THERAPEUTICS, LLC
Reel/Frame 069359/0921 →
SECURITY INTEREST Recorded Aug 6, 2021
From: NEURELIS, INC.; AEGIS THERAPEUTICS, LLC
To: ORBIMED ROYALTY & CREDIT OPPORTUNITIES III, LP
Reel/Frame 057111/0242 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2021
From: ROSEN, KENNETH M.; RIESINGER, STEVEN WAYNE; MCKERRACHER, LISA; BOND MORITZ, LISA
To: BIOAXONE BIOSCIENCES, INC.
Reel/Frame 056773/0985 →
Continuity (7)
Continuation 16214973 · Dec 10, 2018
Continuation 15590815 · May 9, 2017
Continuation In Part 15006314 · Jan 26, 2016
Provisional Application 62286607 · Jan 25, 2016
Provisional Application 62185857 · Jun 29, 2015
Provisional Application 62107571 · Jan 26, 2015
Related Publication 20210290635A1 · Sep 23, 2021