Tissue factor compositions and methods
View Patent ↗Tissue Factor (natural or recombinant truncated) can be incorporated into stable, soluble nanoscale particles so that activity is maintained. These particles can be used as a reagent in prothrombin clotting time assays or they can be used in therapeutic compositions for use in humans or animals. Therapeutic settings can include supplementation in the case of a genetic deficiency, uncontrolled bleeding, surgical incisions or seepage, thrombocytopenia, soft tissue trauma or other trauma, to effect tumor regression or to inhibit tumor growth.
1. A method for controlling bleeding in a human or animal patient, said method comprising the step of administering, in an amount effective to control bleeding in said patient a composition comprising nanoscale particles comprising tissue factor or recombinant tissue factor, a membrane scaffold protein and phospholipid, wherein the phospholipid comprises a net-negatively charged phospholipid, and wherein said nanoscale particles are attached to a solid support, whereby bleeding in said patient is controlled.
2. The method of claim 1 , wherein the phospholipid comprises from 1 to 50% on a molar basis of net-negative charged phospholipid and from 50 to 99% net-neutral phospholipid.
3. The method of claim 1 , wherein the phospholipid consists essentially of phosphatidylserine and phosphatidylcholine or phosphatidylserine and phosphatidylethanolamine in a molar ratio of 20:80 or consists essentially of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine in a molar ratio of 20:40:40.
4. The method of claim 1 , wherein the human or animal patient has hemophilia, a thrombocytopenia or other bleeding diathesis.
5. The method of claim 1 , wherein the patient has a surgical, wound or soft tissue trauma resulting in bleeding.
6. The method of claim 1 , wherein the solid support is a collagen containing material.
7. The method of claim 1 , wherein the membrane scaffold protein comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4, SEQ ID NO:6, SEQ ID NO:8, amino acids 13-414 of SEQ ID NO:8, SEQ ID NO:10, amino acids 13-422 of SEQ ID NO:10, SEQ ID NO:12, amino acids 13-168 of SEQ ID NO:12, SEQ ID NO:14, amino acids 13-168 of SEQ ID NO:14, SEQ ID NO:16, amino acids 13-201 of SEQ ID NO:16, SEQ ID NO:17, amino acids 13-201 of SEQ ID NO:17, SEQ ID NO:18, amino acids 13-392 of SEQ ID NO:18, SEQ ID NO:50, amino acids 13-234 of SEQ ID NO:50, SEQ ID NO:51, amino acids 13-256 of SEQ ID NO:51, SEQ ID NO:52, amino acids 13-278 of SEQ ID NO:52, SEQ ID NO:53, amino acids 24-223 of SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, amino acids 24-212 of SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, amino acids 24-201 of SEQ ID NO:57, SEQ ID NO:58, amino acids 13-190 of SEQ ID NO:58, SEQ ID NO:59, amino acids 13-201 of SEQ ID NO:59, SEQ ID NO:60, amino acids 13-190 of SEQ ID NO:60, SEQ ID NO:61, amino acids 24-201 of SEQ ID NO:61, SEQ ID NO:62, amino acids 24-190 of SEQ ID NO:62, SEQ ID NO:63, amino acids 24-179 of SEQ ID NO:63, SEQ ID NO:64, amino acids 24-289 of SEQ ID NO:64, SEQ ID NO:65, amino acids 24-289 of SEQ ID NO:64, SEQ ID NO:65, amino acids 24-278 of SEQ ID NO:65, SEQ ID NO:66, amino acids 24-423 of SEQ ID NO:66, SEQ ID NO:67, amino acids 24-199 of SEQ ID NO:67, SEQ ID NO:68, amino acids 24-401 of SEQ ID NO:68, SEQ ID NO:69, amino acids 24-392 of SEQ ID NO:69, SEQ ID NO:81, amino acids 24-397 of SEQ ID NO:81, SEQ ID NO:83, amino acids 24-383 of SEQ ID NO:83, SEQ ID NO:85, amino acids 24-379 of SEQ ID NO:85, SEQ ID NO:87, amino acids 24-381 of SEQ ID NO:87, SEQ ID NO:89, amino acids 25-212 of SEQ ID NO:89, SEQ ID NO:91, amino acids 25-212 of SEQ ID NO:91, SEQ ID NO:93 and amino acids 13-212 of SEQ ID NO:93.
8. The method of claim 1 , wherein the tissue factor is a recombinant tissue factor consisting of amino acids 23 to 277 of SEQ ID NO:95.