Granted Patent
B2
US 12,576,130 · App. 16/757,254 · Granted Mar 17, 2026
Dominant negative SARM1 molecules comprising a substitution at position 189, 190, 193, 194, 570 and/or 685 of SARM1
Inventors:
Aaron DiAntonio (St. Louis, MO); Jeffrey D. Milbrandt (St. Louis, MO); Daniel Summers (St. Louis, MO); Stefanie Geisler (St. Louis, MO); Xianrong Mao (St. Louis, MO)
Assignee:
Washington University
A61K38/1709A61K35/76A61K38/1761A61K38/18A61P25/00C07K14/435C07K14/47C07K14/475C07K14/71C12N15/00C12N15/86A61K38/00
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Abstract
The present invention provides compositions useful as inhibitors of SARM1 activity, pharmaceutical compositions thereof, and methods of using the same. The present invention provides dominant negative SARM1 molecules useful for treating a neurodegenerative or neurological disease or disorder, pharmaceutical compositions thereof, and methods of using the same.
Claims (15)
1 . A mutant human sterile alpha and TIR motif containing protein 1 (SARM1) polypeptide, comprising the amino acid sequence of SEQ ID NO:1 and having
an amino acid substitution selected from K193A, K193E, K193M, K193Q, and K193R relative to SEQ ID NO:1;
an amino acid substitution selected from H685Y and H685A relative to SEQ ID NO: 1;
amino acid substitutions K193R and H685A relative to SEQ ID NO:1;
amino acid substitutions K193R, H194A, and H685A relative to SEQ ID NO:1;
an amino acid substitution E189K relative to SEQ ID NO:1; an amino acid substitution R570A relative to SEQ ID NO: 1; or
an amino acid substitution H190A relative to SEQ ID NO:1.
2 . The polypeptide of claim 1 , having the amino acid substitution selected from K193A, K193E, K193M, K193Q, and K193R.
3 . The polypeptide of claim 1 , having the amino acid substitution R570A.
4 . The polypeptide of claim 1 , having the amino acid substitutions K193R and H685A.
5 . The polypeptide of claim 1 , having the amino acid substitution selected from H685A and H685Y.
6 . The polypeptide of claim 1 , having the amino acid substitutions K193R, H194A, and H685A.
7 . The polypeptide of claim 1 , having the amino acid substitution E189K.
8 . The polypeptide of claim 1 , having the amino acid substitution H190A.
9 . A composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable excipient.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 11, 2020
From: DIANTONIO, AARON; MILBRANDT, JEFFREY D.; SUMMERS, DANIEL; GEISLER, STEFANIE; MAO, XIANRONG
To: WASHINGTON UNIVERSITY
Reel/Frame 053454/0618 →
CONFIRMATORY LICENSE
Recorded Jun 4, 2020
From: WASHINGTON UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 052833/0871 →
Continuity (3)
Provisional Application
62644090
· Mar 16, 2018
Provisional Application
62573967
· Oct 18, 2017
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