Antibodies that specifically bind hedgehog-derived polypeptides
AssigneesThe Johns Hopkins University School of Medicine, University of Washington
InventorsPhilip A. Beachy, Jeffrey A. Porter, Randall T. Moon
Life of this patent
Estimating the term…
Abstract
The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G′CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.
Claims15
An isolated antibody fragment which binds specifically to:
- a) an N-terminal fragment of a vertebrate hedgehog polypeptide or a fragment thereof, wherein the N-terminal fragment or the fragment thereof, has a Glycine reside at its carboxy terminus, resulting from specific cleavage of a G↓CF cleavage site specifically recognized by a proteolytic activity of the carboxy terminal fragment of a native hedgehog polypeptide;
- or
- b) a C-terminal fragment of a vertebrate hedgehog polypeptide or a fragment thereof, wherein the C-terminal fragment or the fragment thereof, has Cys Phe residues at its amino terminus, resulting from specific cleavage of a G↓CF cleavage site contained within the hedgehog polypeptide.
A method of generating an antibody fragment which binds specifically to:
- al an N-terminal fragment of a vertebrate hedgehog polypeptide or a fragment thereof, wherein the N-terminal fragment or the fragment thereof, has a Glycine reside at its carboxy terminus, resulting from specific cleavage of a G↓CF cleavage site specifically recognized by a proteolytic activity of the carboxy terminal fragment of a native hedgehog polypeptide;
- or
- b) a C-terminal fragment of a vertebrate hedgehog polypeptide or a fragment thereof, wherein the C-terminal fragment or the fragment thereof, has Cys Phe residues at its amino terminus, resulting from specific cleavage of a G↓CF cleavage site contained within the hedgehog polypeptide,
- comprising immunizing a mammalian subject with the N-terminal fragment or the fragment thereof, or the C-terminal fragment or the fragment thereof.
Dependencies are inferred from the claim text.