New York Blood Center, Inc.

New York Blood, Inc.

Alessandra Bini

Bohdan J Kudryk

The invention provides monoclonal antibodies which are reactive with fibrin(ogen) degradation products (FDPS) generated by matrix metalloproteinases (MMPs), such as MMP-3, MMP-7, and membrane-type 1, MT1-MMP proteolysis of fibrinogen and cross-linked fibrin (and not plasmin or other proteases). Monoclonal antibodies of the invention include, but are not limited to, H5, F2, 90/2, 90/5, B4, 13, C6, A6, G6, E6, 197-1 and 197-2. This invention also provides methods of using monoclonal antibodies for detection of FDPs generated by proteolysis of fibrin(ogen) by MMPs, such as MMP-3, MMP-7, and MT1-MMP. In addition, the present invention provides methods for diagnosing rheumatoid arthritis, osteoarthritis, and synovitides, as well as angiogenesis, atherosclerosis, renal diseases, malignancy and inflammation. The present invention also provides methods for diagnosing fibrin formation and degradation in physiological processes such as in wound healing deficiencies and abnormalities, and in development of human placenta and in pregnancy diseases.

Monoclonal antibodies reactive with fibrin (ogen) degradation products generated by matrix metalloproteinases

The invention provides a monospecific antibody that is specifically reactive with enzymatically mediated degradation products of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances). The monospecific antibody of the invention is specifically reactive with an epitope defined by an amino acid sequence SEQ ID NO:1. The invention further provides compositions containing a monospecific antibody, optionally detectably labeled, for the performance of fibrinolytic or thrombolytic analyses. The invention further provides continuous cell lines (hybridomas) that produce monospecific antibodies as described.

Monospecific antibody reactive with matrix metalloproteinase cleavage

The invention provides a method of causing the degradation of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances) by means of a fibrinolytic matrix metalloproteinase, preferably an MMP-3 or MMP-7. The method of the invention can be performed in vitro to provide diagnostic information characterizing fibrin(ogen) and fibrinolytic physiology. The method can also be performed in vivo as a method of thrombolytic therapy in which a fibrinolytic matrix metalloproteinase is administered to a subject to degrade thrombus in situ. The fibrinolytic matrix metalloproteinase can be administered in conjunction with other active agents, preferably with agents having thrombolytic activity to improve thrombolytic and fibrinolytic therapy. The invention further provides compositions containing a fibrinolytic matrix metalloproteinase for the performance of fibrinolytic or thrombolytic procedures. Also provided are kits that include a fibrinolytic matrix metalloproteinase for performing fibrinolytic or thrombolytic procedures.

Inhibition of thrombus formation by medical related apparatus comprising

The invention provides a method of causing degradation of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances) by means of a fibrinolytic metalloproteinase, preferably an endogenous metalloproteinase such as MMP-3. The method of the invention can be performed in vitro to provide diagnostic information characterizing fibrin(ogen) and fibrinolytic physiology. The method can also be performed in vivo as a method of thrombolytic therapy in which a fibrinolytic metalloproteinase is administered to a subject to degrade thrombus in situ. The endogenous fibrinolytic metalloproteinase can be administered in conjunction with other active agents, preferably with agents having thrombolytic activity to improve thrombolytic and fibrinolytic therapy. The invention further provides compositions containing a fibrinolytic metalloproteinase for the performance of fibrinolytic or thrombolytic procedures. Also provided are kits which include a fibrinolytic metalloproteinase for performing fibrinolytic or thrombolytic procedures.

Fibrin(ogen) degradation and clot lysis by fibrinolytic matrix

The invention provides a method of causing the degradation of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances) by means of a fibrinolytic metalloproteinase, such as MMP-3. The method of the invention may be performed in vitro to provide diagnostic information characterizing fibrin(ogen) and the fibrinolytic physiology. The method may also be performed in vivo as a method of thrombolytic therapy in which a fibrinolytic metalloproteinase is administered to a subject to degrade thrombus in situ. The invention further provides compositions containing a fibrinolytic metalloproteinase for the performance of fibrinolytic or thrombolytic procedures. Also provided are kits which include a fibrinolytic metalloproteinase for performing fibrinolytic or thrombolytic procedures.

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New York, NY, United States of America

Alessandra Bini