TNF-α converting enzyme
AssigneeImmunex Corporation
InventorsRoy A. Black, Charles Rauch, Carl J. March, Douglas P. Cerretti
Life of this patent
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Abstract
A metalloprotease that converts TNF-α from the 26 kD cell form to the 17 kD form has been isolated and purified and the cDNA sequence known. In particular, the protease has a molecular weight of approximately 80 kD. The isolated and purified protease is useful for designing an inhibitor thereof, and may find use as a therapeutic agent. Assays for detecting the protease-inhibiting activity of a molecule are also an aspect of the invention.
Claims22
A method for inhibiting the cleavage of a substrate by an isolated and purified polypeptide comprising SEQ ID NO:9 and capable of converting TNF-α from the 26 kD form to the 17 kD form, the method comprising forming a mixture of said polypeptide, a substrate, and a compound, wherein the compound inhibits the cleavage of said substrate by said polypeptide.
A method for inhibiting the cleavage of a substrate by an isolated and purified polypeptide, the method comprising forming a mixture of said polypeptide, a substrate, and a compound, wherein the compound inhibits the cleavage of said substrate by said polypeptide, and wherein the polypeptide comprises an amino acid sequence selected from the group consisting of:
- (a) the amino acid sequence of SEQ ID NO:2;
- (b) the amino acid sequence of SEQ ID NO:2 from amino acid 215 to amino acid 477;
- (c) the amino acid sequence of SEQ ID NO:2 from amino acid 18 to amino acid 477;
- (d) the amino acid sequence of SEQ ID NO:2 from amino acid 18 to amino acid 671;
- (e) the amino acid sequence of SEQ ID NO:2 from amino acid 18 to amino acid 824;
- (f) the amino acid sequence of SEQ ID NO:2 from amino acid 18 to Xaa, wherein Xaa is an amino acid from 671 to 824;
- (g) a fragment of SEQ ID NO:2 such that a polypeptide with an amino acid sequence consisting of said fragment is capable of converting TNF-α from the 26 kD form to the 17 kD form;
- (h) SEQ ID NO:4;
- (i) a fragment of SEQ ID NO:4 such that a polypeptide with an amino acid sequence consisting of said fragment is capable of converting TNF-α from the 26 kD form to the 17 kD form;
- (j) an amino acid sequence that is at least 80% identical to the amino acid sequence of any of (a)-(i), such that a polypeptide consisting of said amino acid sequence is capable of converting TNF-α from the 26 kD form to the 17 kD form;
- and
- (k) an amino acid sequence that is at least 90% identical to the amino acid sequence of any of (a)-(i), such that a polypeptide consisting of said amino acid sequence is capable of converting TNF-α from the 26 kD form to the 17 kD form.
A method for inhibiting the cleavage of a substrate by an isolated and purified polypeptide, the method comprising forming a mixture of said polypeptide, a substrate, and a compound, wherein the compound inhibits the cleavage of said substrate by said polypeptide, and wherein the polypeptide comprises an amino acid sequence selected from the group consisting of:
- (a) the amino acid sequence of SEQ ID NO:2 from amino acid 215 to amino acid 477;
- (b) the amino acid sequence of SEQ ID NO:2 from amino acid 18 to Xaa, wherein Xaa is an amino acid from 671 to 824;
- (c) a fragment of SEQ ID NO:2 such that a polypeptide with an amino acid sequence consisting of said fragment is capable of converting TNF-α from the 26 kD form to the 17 kD form;
- (d) SEQ ID NO:4;
- and
- (e) a fragment of SEQ ID NO:4 such that a polypeptide with an amino acid sequence consisting of said fragment is capable of converting TNF-α from the 26 kD form to the 17 kD form.
Dependencies are inferred from the claim text.