Alternatively spliced circulating tissue factor - Patents

Alternatively spliced circulating tissue factor
nited States Patent 7,045,350
Nemerson , et al.
May 16, 2006
Inventors: Nemerson; Yale (New York, NY); Bogdanov; Vladimir (New York, NY)
Assignee: Mount Sinai School of Medicine of New York University (New York, NY)
Appl. No.: 230839
Filed: August 29, 2002
Abstract
A new circulating form of soluble human tissue factor was identified. This new form of human tissue factor appears to be the result of alternative splicing and is therefore referred to as "alt-hTF." Alt-hTF mRNA was detected in a cell line, HL-60. The cDNA region encoding the entire open reading frame of alt-hTF was cloned. The sequence encoding the alt-hTF mature peptide was expressed in bacteria. alt-hTF consists of the first 166 amino acids of membrane bound TF, and a 40 amino acid C-terminal region unique to alt-hTF. Alt-hTF is likely to be a useful target for compounds to inhibit clotting and to treat disorders associated with elevated TF. It may also be useful as a target for antibodies selectively reactive with alt-hTF, to remove it from the circulation for treatment of clotting or other disorders associated with elevated or abnormal levels of TF, including thrombotic conditions, cardiovascular disorders, DVT, DIC, and possibly metastatic cancers.