The General Hospital Corporation

Harvard College

Bristol-myers Squibb Compnay

Guy L Reed

Gary R Matsueda

Edgar Haber

Christophe Y Clement

Jurgen Bajorath

Linda Harris

Mei-Yin Hsu

Jiri Novotny

A substantially pure platelet activation polypeptide including a sequence at least 70% identical to SEQ ID NO:1, and a DNA encoding such a polypeptide.

Platelet activation protein

The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to &agr;2-antiplasmin crosslinked to fibrin (&agr;2AP-FX) which does not inhibit plasma &agr;2-antiplasmin (&agr;2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward &agr;2-antiplasmin crosslinked to fibrin which does not inhibit plasma &agr;2AP together with a thrombolytic agent.

Antibodies that bind to &agr;2-antiplasmin crosslinked to fibrin which do not inhibit plasma &agr;2-antiplasmin

The invention provides methods of detecting blood in vivo and methods of inhibiting clot formation and promoting therapeutic thrombolysis using alpha-2 antiplasmin (&agr;2AP) polypeptides.

Methods of inhibiting clot formation

A pharmaceutical composition in a preferred embodiment comprises an isolated bacterial protein that induces fibrin-dependent plasminogen activation, and methods for dissolving blood clots in a subject use such a composition. Embodiments also include a nucleic acid encoding such a bacterial protein, a nucleic acid encoding such a bacterial protein as a fusion to another protein, an expression vector with the nucleic acid, and a host cell transformed with the expression vector.

Bacterial fibrin-dependent plasminogen activator

The present invention relates to a novel alpha-2-antiplasmin-binding molecules and treatment for pulmonary embolism, myocardial infarction, thrombosis or stroke in a patient which comprises administering an alpha-2-antiplasmin-binding molecule capable of preventing inhibition of plasmin by endogenous alpha-2-antiplasmin. The invention also relates to a treatment for pulmonary embolism, myocardial infarction, thrombosis or stroke in a patient comprising coadministrating an alpha-2-antiplasmin-binding molecule of the invention together with a thrombolytic agent.

Composition and method for enhancing fibrinolysis

Disclosed is a novel protein designated platelet secretory transport protein (PSTP). PSTP occurs in platelets and binds to syntaxin. An isolated DNA encoding PSTP, vectors and cells containing the DNA, and PSTP specific antibodies are also disclosed. A PSTP antibody can be used to target a compound to an activated platelet in a mammal for diagnostic or therapeutic purposes. Also disclosed is an in vitro screening method for identifying a compound that inhibits PSTP-syntaxin binding, and an in vitro method for identifying a compound that inhibits PSTP gene expression.

Platelet secretory transport protein

The invention features modified streptokinase (SK) molecules which are resistant to plasmin cleavage including a recombinant fusion protein in which the amino terminus of SK was blocked with a peptide, a recombinant fusion protein in which an amino-terminal deleted SK was blocked with a peptide, and a mutated SK in which plasmin-cleavage sites were altered to render those sites resistant to enzymatic cleavage.

Plasmin-resistant streptokinase

The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to .alpha.2-antiplasmin crosslinked to fibrin (.alpha.2AP-FX) which does not inhibit plasma .alpha.2-antiplasmin (.alpha.2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward .alpha.2-antiplasmin crosslinked to fibrin which does not inhibit plasma .alpha.2AP together with a thrombolytic agent.

Antibodies that bind to .alpha.2-antiplasmin crosslinked to fibrin which

Display case for photographs and cards resembling a baseball bat

The present invention provides a thrombin-activated platelet protein (TAPP). The protein is selectively expressed on the surface of thrombin-activated platelets. Antibodies which selectively bind to the thrombin-activated platelet protein are also provided. These compositions find use in the detection and treatment of blood clots.

Activation-dependent protein expressed on the surface of activated

Methods of inhibiting the activation of Factor XIII

The present invention relates to a treatment for myocardial infarction and blood clots within a patient, and more specifically to a therapy which enhances clot lysis comprising administering to a patient an antibody directed to .alpha.2-antiplasmin crosslinked to fibrin (.alpha.2AP-Fx) which does not inhibit plasma .alpha.2-antiplasmin (.alpha.2AP). The invention also relates to a treatment for enhancing clot lysis comprising administering an antibody directed toward .alpha.2-antiplasmin crosslinked to fibrin which does not inhibit plasma .alpha.2AP together with a thrombolytic agent.

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Winchester, MA, United States of America

Guy L Reed