Granted Patent
B2
US 12,570,741 · App. 17/823,824 · Granted Mar 10, 2026
NOTCH3 agonist compositions and methods for treating small vessel diseases
Assignee:
Massachusetts Eye and Ear Infirmary
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Abstract
The present subject matter provides, inter alia, compositions, formulations, and methods for inhibiting, treating, and preventing small vessel diseases.
Claims (15)
1 . A method for treating a small vessel disease (SVD) in a subject, comprising administering to the subject an effective amount of a Neurogenic Locus Notch Homolog Protein 3 (NOTCH3) agonist polypeptide comprising a polypeptide comprising the extracellular domain of DELTA-LIKE4 (SEQ ID NO: 23) or a fragment thereof comprising a stretch of amino acids having the sequence CSDNYYGDNCSRLCKKR (SEQ ID NO:8).
2 . The method of claim 1 , wherein the SVD is cerebral SVD.
3 . The method of claim 2 , wherein the cerebral SVD is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), or cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
4 . The method of claim 1 , wherein the subject has a loss-of-function mutation in NOTCH3.
5 . The method of claim 1 , wherein the subject has diabetic retinopathy, age-related macular degeneration (AMD), nephropathy, microangiopathy, heart failure, Alagille syndrome, familial tetralogy of Fallot, patent ductus arteriosus, or a cerebral cavernous malformation.
6 . The method of claim 1 , wherein the subject comprises a level of collagen18α1, endostatin, NOTCH3, N3ECD, IGFBP-1, HTRA1, and/or NF-L protein or mRNA that is different than a normal control.
7 . The method of claim 1 , wherein the extracellular domain of DELTA-LIKE4 or fragment thereof comprises a stretch of amino acids having the sequence CSDNYYGDNCSRLCKKRNDHFGH (SEQ ID NO:9).
8 . The method of claim 7 , wherein the SVD is cerebral SVD.
9 . The method of claim 8 , wherein the cerebral SVD is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), or cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
10 . The method of claim 1 , wherein the agonist polypeptide consists of CSDNYYGDNCSRLCKKR (SEQ ID NO:8).
11 . The method of claim 10 , wherein the SVD is cerebral SVD.
12 . The method of claim 11 , wherein the cerebral SVD is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), or cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
13 . The method of claim 1 , wherein the agonist polypeptide consists of CSDNYYGDNCSRLCKKRNDHFGH (SEQ ID NO:9).
14 . The method of claim 13 , wherein the SVD is cerebral SVD.
15 . The method of claim 14 , wherein the cerebral SVD is cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), or cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 16, 2025
From: THE SCHEPENS EYE RESEARCH INSTITUTE, INC.
To: MASSACHUSETTS EYE AND EAR INFIRMARY
Reel/Frame 073235/0936 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 3, 2023
From: ARBOLEDA-VELASQUEZ, JOSEPH F.
To: THE SCHEPENS EYE RESEARCH INSTITUTE, INC.
Reel/Frame 062256/0557 →
Continuity (3)
Continuation
16499225
Provisional Application
62477289
· Mar 27, 2017
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