New York Blood Center, Inc.

Bohdan J Kudryk

Gerd Grieninger

Yiping Fu

Yan Cao

Mohamad Zaher Ahadi

Alessandra Bini

Michael E Wiebe

Colvin M Redman

Roman Procyk

Jian-Zhong Zhang

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

An assay method that requires a soluble fibrin monomer or a soluble fibrin monomer reagent as one of the components of the assay. The reagent is a fibrin-like material having a solubility and stability similar to fibrinogen in that it remains soluble and stable at physiological conditions at a concentration employed in the assay in the absence of fibrin polymerization inhibitors or reagents for maintaining solubility.

Assays using a soluble fibrin-like monomer

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 monospecific antibodies which are specifically reactive with the .alpha.hd E subunit of fibrinogen or a fragment thereof, but not with other portions of the fibrinogen molecule. The invention also provides anti-.alpha..sub.E probes, including monospecific anti-.alpha..sub.E antibodies which have been detectably labeled. In addition, the invention provides methods of using the monospecific antibodies for detection of the .alpha..sub.E subunit and fragments thereof, as well as reagents and kits for performing the methods. Diagnostic methods for determining information associated with atherogenesis and/or thrombogenesis, as well as for determining information associated with pregnancy status or outcome. The invention further provides continuous cell lines which produce monospecific anti-.alpha..sub.E antibodies.

Monospecific antibodies against a subunit of fibrinogen

The invention provides monospecific antibodies which are specifically reactive with the .alpha..sub.E subunit of fibrinogen or a fragment thereof, but not with other portions of the fibrinogen molecule. The invention also provides anti-.alpha..sub.E probes, including monospecific anti-.alpha..sub.E antibodies which have been detectably labeled. In addition, the invention provides methods of using the monospecific antibodies for detection of the .alpha..sub.E subunit and fragments thereof, as well as reagents and kits for performing the methods. Diagnostic methods for determining information associated with atherogenesis and/or thrombogenesis, as well as for determining information associated with pregnancy status or outcome. The invention further provides continuous cell lines which produce monospecific anti-.alpha..sub.E antibodies.

The invention provides monospecific antibodies that are specifically reactive with fibrinopeptide B (FPB) and with fibrinogen and fragments thereof containing the amino acid sequence defined by SEQ ID NO:1. The invention also provides anti-FPB probes, including monospecific anti-FPB antibodies that have been detectably labeled. In addition, the invention provides methods of using the monospecific antibodies for detection of fibrinopeptide B, as well as reagents and kits for performing the methods. For example, the invention provides a method for detecting fibrinopeptide B with specificity in biological samples such as blood samples, by using the antibody to immunometrically bind to the fibrinopeptide B. Diagnostic methods for determining information associated with atherogenesis and/or thrombogenesis. The invention further provides continuous cell lines (hybridomas) that produce monospecific anti-FPB antibodies.

Monospecific antibody reactive with Fibrinogen and fibrinopeptide B

The invention provides nonspecific antibodies which are specifically reactive with the .alpha..sub.E subunit of fibrinogen or a fragment thereof, but not with other portions of the fibrinogen molecule. The invention also provides anti-.alpha..sub.E probes, including nonspecific anti-.alpha..sub.E antibodies which have been detectably labeled. In addition, the invention provides methods of using the nonspecific antibodies for detection of the .alpha..sub.E subunit and fragments thereof, as well as reagents and kits for performing the methods. Diagnostic methods for determining information associated with atherogenesis and/or thrombogenesis, as well as for determining information associated with pregnancy status or outcome. The invention further provides continuous cell lines which produce monospecific anti-.alpha..sub.E antibodies.

Hybridoma for production of monoclonal antibody to an antigen found on the peptide fragment of the B.beta. chain of human fibrinogen or fibrin I containing amino acid residues 1-42. The hybridoma is formed by fusing an animal myeloma cell, e.g., mouse myeloma cell, with a splenocyte from an animal, e.g., a mouse, immunized with an NH.sub.2 -terminal of human fibrinogen or fibrin I. Hybridoma for production of monoclonal antibody to an antigen found on the peptide fragment of the B.beta. chain of human fibrin II containing amino acid residues 15-42. The hybridoma is formed by fusing an animal, e.g., mouse myeloma cell with a splenocyte from an animal, e.g., mouse, immunized with a NH.sub.2 -terminal of human fibrin II. Diagnostic and therapeutic uses of the monoclonal antibodies are also disclosed.

Monoclonal antibodies specific to in vivo fragments derived from human

Hybridoma for production of monoclonal antibody to an antigen found on the peptide fragment of the B.beta. chain of human fibrinogen or fibrin I containing amino acid residues 1-42. The hybridoma is formed by fusing an animal myeloma cell, e.g., a mouse myeloma cell, with a splenocyte from an animal, e.g., a mouse, immunized with an NH.sub.2 -terminal of human fibrinogen or fibrin I. Hybridoma for production of monoclonal antibody to an antigen found on the peptide fragment of the B.beta. chain of human fibrin II containing amino acid residues 15-42. The hybridoma is formed by fusing an animal, e.g., mouse myeloma cell with a splenocyte from an animal, e.g., mouse, immunized with a NH.sub.2 -terminal of human fibrin II. Diagnostic and therapeutic uses of the monoclonal antibodies are also disclosed.

Growing community of inventors

Hillsdale, NJ, United States of America

Bohdan J Kudryk