David M Crawford

US Patent:

54478510, Sep 5, 1995

Filed:

Apr 2, 1992

Appl. No.:

7/862495

Inventors:

Bruce A. Beutler - Dallas TX
Karsten Peppel - Dallas TX
David F. Crawford - Irving TX

Assignee:

Board of Regents, The University of Texas System - Austin TX

International Classification:

C12P 2106
C12N 1500
C07H 1700
C07K 1400

US Classification:

435 697

Abstract:

The invention relates generally to DNA sequences encoding chimeric polypeptides comprising extracellular portions of cytokine receptor polypeptides attached to a sequence encoding portions of IgG polypeptides. The invention relates generally, as well, to DNA sequences encoding chimeric polypeptides comprising extracellular portions of cytokine receptor polypeptides attached through oligomers encoding specifically cleavable peptide linkers to a sequence encoding portions of IgG heavy chain polypeptides More specifically, the invention relates to a construction in which a cDNA sequence encoding the extracellular domain of the human 55 kD TNF receptor is attached through an oligomer encoding a thrombin-sensitive peptide linker to a sequence encoding the F. sub. c portion and hinge region of a mouse IgGl heavy chain. The invention relates as well to uses of the chimeric polypeptide, including: use as a reagent for the antagonism and assay of TNF and lymphotoxin from diverse species; use as a means of determining the mechanism by which TNF, or analogs thereof, interacts with the TNF receptor; use as an antitumor reagent, particularly against placental tumors; and, use as a reagent capable of controlling birth.