Functional antagonists of hedgehog activity
AssigneeCuris, Inc.
InventorsKevin Williams, Paul Rayhorn, Ellen A. Garber, R. Blake Pepinsky
Life of this patent
Estimating the term…
Abstract
Variants of hedgehog protein that contain N-terminal modifications are described that can block hedgehog function; thus allowing these variants to serve as functional antagonists. These peptides have a primary amino acid sequence lacking the ability to elicit a hedgehog-dependent response in C3H 10T1/2 cells but having the ability to bind to the hedgehog receptor, patched-1. Methods for producing such functional antagonists and methods of using the functional antagonists are also described.
Claims41
A sterile pharmaceutical composition comprising:
- a.) an isolated, functional antagonist of a hedgehog polypeptide, wherein said antagonist can bind to a hedgehog receptor, but does not induce a hedgehog-dependent signaling response, wherein said antagonist is a polypeptide comprising an amino acid sequence represented in any of SEQ ID NOs:
- 1-8 or 11, and wherein a residue of said antagonist corresponding to Cys-1 of a mature hedgehog polypeptide is deleted;
- and
- b.) one or more pharmaceutically acceptable carriers.
A sterile pharmaceutical composition consisting of (i) a functional antagonist of a hedgehog polypeptide, wherein the antagonist can bind to a hedgehog-responsive receptor, but cannot induce a hedgehog-dependent signaling response, wherein said antagonist is a polypeptide consisting of an amino acid sequence represented in any of SEQ ID NO:s 1-8 or 11, and wherein a residue of said antagonist corresponding to Cys-1 of a mature hedgehog polypeptide is deleted;
- and (ii) one or more pharmaceutically acceptable carriers.
A sterile pharmaceutical composition consisting of (i) a functional antagonist of a hedgehog polypeptide, wherein said antagonist is a polypeptide consisting of an amino acid sequence selected from any of SEQ ID NOS:
- 5, 6, 7, 9 and 11;
- and (ii) one or more pharmaceutically acceptable carriers.
A sterile pharmaceutical composition comprising:
- a.) an isolated, functional antagonist of a hedgehog polypeptide, wherein said antagonist has the following properties:
- (i) the isolated antagonist binds a hedgehog receptor;
- and
- (ii) the isolated antagonist blocks alkaline phosphatase (AP) induction by mature hedgehog protein when tested in an AP assay,
- wherein said antagonist is a polypeptide comprising an amino acid sequence represented in any of SEQ ID NOs:
- 1-8 or 11, and wherein a residue of said antagonist corresponding to Cys-1 of a mature hedgehog polypeptide is deleted and
- b.) a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.