Binding proteins specific for human matriptase

Inventors

Foltz, Ian • King, Chadwick • Ling, Peter Koon Bong • Kang, Jaspal Singh • Manchulenko, Kathy • Chen, Francine • Scatena, Caroline Darne • Keyt, Bruce A. • Madison, Edwin • Godfrey, Wayne R. • Morkowski, Stanislaw K. • Richardson, Jennifer H.

Assignees

Amgen Fremont Inc • Dendreon Pharmaceuticals LLC

Abstract

Binding proteins, such as fully human monoclonal antibodies and fragments thereof, directed to the antigen Matriptase and uses of such binding proteins are disclosed. Nucleotide sequences encoding, and amino acid sequences comprising heavy and light chain immunoglobulin molecules capable of binding to Matriptase are also disclosed. The invention also discloses cell lines expressing such immunoglobulin molecules and monoclonal antibodies to Matriptase. The antibodies can be used to detect, prevent, and treat diseases such as cancer.

Core Innovation

The invention provides fully human high-affinity neutralizing binding proteins specific for human Matriptase (MT-SP1; Tumor-Associated differentially expressed Gene-15). The binding proteins include monoclonal antibodies and antibody fragments that specifically bind to and neutralize the Matriptase catalytic domain.

The monoclonal antibodies comprise defined heavy chain and light chain polypeptides using sequence sets set forth in SEQ ID NO:4 and SEQ ID NO:6 or in SEQ ID NO:8 and SEQ ID NO:10. The disclosure further includes encoded nucleic acids, expressing cell lines, and binding and neutralization behavior directed to the Matriptase catalytic domain.

The stated functional activities include inhibiting Matriptase-dependent cell migration and neutralizing Matriptase enzymatic activity. The disclosed antibodies are characterized by low or non-measurable immunogenicity, including reduced human anti-human antibody (HAHA) response, and include cross-reactivity described to a rhesus ortholog and measurements of affinity and inhibition.

Claims Coverage

The document contains one independent claim directed to a Matriptase-neutralizing monoclonal antibody that specifically binds and neutralizes the Matriptase catalytic domain using defined heavy- and light-chain sequence sets, with dependent claims further covering alternative binding-fragment formats, nucleic acids, assay kit detection, and an immune-response constraint. The inventive features in the independent claim focus on catalytic-domain specificity and neutralization using the stated sequence sets, while dependents expand scope to additional molecular formats and use as a detection kit.

Overall claim coverage centers on monoclonal antibodies or binding fragments that specifically bind and neutralize the Matriptase catalytic domain using the stated heavy- and light-chain sequence sets (SEQ ID NO:4/SEQ ID NO:6 or SEQ ID NO:8/SEQ ID NO:10). Dependent claims additionally cover binding-fragment formats, nucleic acids encoding the chains, an assay kit for Matriptase detection in mammalian tissues or cells using the antibody, and an immune-response constraint based on lack of detectable HAHA immune response.

Stated Advantages

Documented Applications