Medimmune Limited

Bayer Pharmaceutical Corporation

Julie Rinkenberger

Ian Nevin Foltz

Vahe Bedian

Simon Thomas Barry

Avril Alfred

Toshihiko Takeuchi

John E Murphy

Nathalie Dubois-Stringfellow

Targeted binding agents, such antibodies directed to the antigen &#x3b1;V&#x3b2;6 and uses of such agents are described. In particular, fully human monoclonal antibodies directed to the antigen &#x3b1;V&#x3b2;6 are disclosed. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3 are disclosed. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also disclosed.

Antibodies directed to &#x3b1;V&#x3b2;6 and uses thereof

The invention is composed of monoclonal human MN antibodies or MN antibody fragments that target the GEEDLP (SEQ ID NO: 118) repeat within the proteoglycan domain. The proteoglycan domain of the MN cell surface protein contains four of these identical GEEDLP (SEQ ID NO: 118) repeats. Binding to the desired epitope is verified by competition ELISA, where ELISA signal can be attenuated by co-incubation with a peptide containing this repeat (PGEEDLPGEEDLP (SEQ ID NO: 119)). This inhibition of binding can also be verified using Biacore assays, where binding of desired antibodies to immobilized MN or proteoglycan peptides can be inhibited by the peptide repeat. In addition to binding to the peptide repeat, human anti-MN antibodies can inhibit the cell adhesion of CGL-1 cells to MN coated plastic plates. Human anti-MN antibodies have been used to diagnose and quantify MN expression in cancer cells and tumors using FACS and immunohistochemical methods. An example is also provided where a human anti-MN IgG1 mediates tumor cell lysis though antibody-dependent cell-mediated cytotoxicity. Therefore, these antibodies will be useful for the treatment of cancers in which MN is upregulated or can be useful for the diagnosis of cancers in which MN is upregulated.

Human antibodies that have MN binding and cell adhesion-neutralizing activity

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Moraga, CA, United States of America

Julie Rinkenberger