American Diagnostica, Inc.

Quebepharma Recherche, Inc.

Robert Greenfield

Seong Soo A An

Clarke Slemon

Jean Vaugeois

Latchezar Trifonov

Enriqueta Guinto

Safi Ranzurmal

Hugh Fryer

The present invention relates generally to the field of diagnostic screening and diagnostic assays. In particular, the present invention provides an improved, rapid, and efficient method of screening for antiphospholipid antibodies, such as lupus anticoagulants (LA). The invention also relates to a kit for screening plasma levels for antiphospholipid antibodies in subjects in need thereof, such as those at risk for or suffering from, inter alia, antiphospholipid syndrome (APS) and systemic lupus erythromatosus (SLE).

Lupus anticoagulant testing

Provided are methods of screening compounds for any aspirin-related activity other than TAFI inhibition, and also for non-inhibition of TAFI. Compounds identified by the screening methods can be used to treat, prevent or manage in a patient pain, fever, colon cancer, pancreatic cancer or an inflammatory, platelet aggregation, fibrinolytic or hemorrhagic disease or disorder. Also provided is a method of evaluating test compounds for TAFI inhibitory activity wherein the TAFI inhibitory activity of these test compounds is compared to the TAFI inhibitory activity of aspirin or its derivatives or metabolites. Further provided is a method of treating, preventing or managing in a patient, a hemorrhagic or thrombotic disease or disorder with high dose aspirin or aspirin derivatives or metabolites. Also contemplated is a method of treating, preventing or managing in a patient, pain, fever, colon cancer, pancreatic cancer or an inflammatory, platelet aggregation, fibrinolytic or hemorrhagic disease or disorder comprising administering aspirin or a derivative thereof or any other therapeutic having at least one desired therapeutic or prophylactic activity of aspirin to a patient in need thereof and administering to the patient a factor that promotes TAFIa activity, e.g. stabilized TAFIa, to ameliorate one or more adverse side effects of the therapeutic. Compounds identified by the methods of the invention are also provided.

Methods of screening for compounds that modulate TAFIa activity, compounds, and methods of using the compounds

The invention relates to a diagnostic assay for selectively measuring levels of the 35kD form of thrombin-activatable fibrinolysis inhibitor (TAFIa or TAFIai), or a derivative or variant thereof, but not the TAFI proenzyme (TAFI) or the N-terminal activation peptide of TAFI.

Methods for detecting TAFIa or TAFIai

Provided are assays to detect ADAMTS13 activity using peptide substrates. These assays can be used for diagnostic applications and to evaluate treatment of thrombotic thrombocytopenic purpura (TTP). Also provided is a novel form of ADAMTS13 found on platelets.

Methods for measuring ADAMTS13 activity and protein on platelets and in plasma

Provided are methods of screening compounds for any aspirin-related activity other than TAFI inhibition, and also for non-inhibition of TAFI. Compounds identified by the screening methods can be used to treat, prevent or manage in a patient pain, fever, colon cancer, pancreatic cancer or an inflammatory, platelet aggregation, fibrinolytic or hemorrhagic disease or disorder. Also provided is a method of evaluating test compounds for TAFI inhibitory activity wherein the TAFI inhibitory activity of these test compounds is compared to the TAFI inhibitory activity of aspirin or its derivatives or metabolites. Further provided is a method of treating, preventing or managing in a patient, a hemorrhagic or thrombotic disease or disorder with high dose aspirin or aspirin derivatives or metabolites. Also contemplated is a method of treating, preventing or managing in a patient, pain, fever, colon cancer, pancreatic cancer or an inflammatory, platelet aggregation, fibrinolytic or hemorrhagic disease or disorder comprising administering aspirin or a derivative thereof or any other therapeutic having at least one desired therapeutic or prophylactic activity of aspirin to a patient in need thereof and administering to the patient a factor that promotes TAFIa activity, e.g. stablized TAFIa, to ameliorate one or more adverse side effects of the therapeutic. Compounds identified by the methods of the invention are also provided.

The invention is directed in part to a purified form of stabilized activated thrombin-activatable fibrinolysis inhibitor (TAFIa). The invention is further directed to a method of producing stabilized TAFIa. The invention is also directed to methods for therapeutic use of stabilized TAFIa such as in the treatment, prevention or management of diseases via an anti-coagulant effect. The invention is also directed to methods for therapeutic use of inhibitors of TAFIa such as in the treatment, prevention or management of diseases via a procoagulant effect. The invention is also directed to methods of diagnostic use of stabilized TAFIa such as a standard in a chromogenic or a fluorometric carboxypeptidase activity assay. The present invention is also directed to kits comprising stabilized TAFIa useful in measuring carboxypepetidase activity.

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Trumbull, CT, United States of America

Robert Greenfield