Tissue Plasminogen Activator Antibodies and Methods of Use
AssigneeUniversity of Tennessee Research Foundation
InventorGuy Reed
Life of this patent
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Abstract
A molecule that binds specifically to a human tissue plasminogen activator (TPA) or a TPA mutant is provided. The molecule having sub-nanomolar affinity to inhibit fibrin-dependent plasminogen activation with an IC50<5 nM, to inhibit degradation of human fibron clots without affecting TPA amidolytic activity or non-fibrin-dependent activation, and the amino acid sequence of the TPA mutant is at least 65% identical to SEQ ID NO: 1 or SEQ ID NO: 2. Further provided is a method for treating systemic bleeding and brain hemorrhage after TPA treatment in a patient in need of such treatment. The method comprises administering to said patient an effective amount of the molecule, wherein the molecule selectively inhibits fibrin-augmented plasminogen activation in the patient.
Claims5
-37. (canceled)
A method for identifying molecules that can inhibit TPA-induced fibrinolysis of human clots, comprising:
- providing a monoclonal antibody that specifically binds to TPA and inhibits TPA-induced fibrinolysis of human clots, wherein the monoclonal antibody is a monoclonal antibody identified as TPAi-14 (ECACC accession number 18042001) or TPAi-23 (ECACC accession number 18042002);
- affixing said monoclonal antibody to a surface;
- providing TPA and introducing an agent to said TPA that blocks the non-specific binding regions of TPA;
- introducing a candidate molecule to said TPA;
- introducing said TPA to said monoclonal antibody;
- determining if said candidate molecule has bound to the epitope of the TPA where said monoclonal antibody had bound to the TPA;
- and
- identifying any candidate molecule binding to said epitope as a molecule that can inhibit TPA-induced fibrinolysis of human clots.
Dependencies are inferred from the claim text.