Anti-alphavbeta3 recombinant human antibodies, nucleic acids encoding same and methods of use

A nucleic acid encoding a Vitaxin heavy chain polypeptide comprising substantially the same Vitaxin heavy chain variable region nucleotide sequences as that shown in FIG. 1A (SEQ ID NO:1) or a fragment thereof.

A nucleic acid encoding a Vitaxin light chain polypeptide comprising substantially the same Vitaxin light chain variable region nucleotide sequences as that shown in FIG. 1B (SEQ ID NO:3) or a fragment thereof.

A nucleic acid encoding a Vitaxin heavy chain polypeptide comprising a nucleotide sequence encoding substantially the same Vitaxin heavy chain variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) or fragment thereof.

A nucleic acid encoding a Vitaxin light chain polypeptide comprising a nucleotide sequence encoding substantially the same Vitaxin light chain variable region amino acid sequence as that shown in FIG. 1B (SEQ ID NO:4) or fragment thereof.

A Vitaxin heavy chain polypeptide comprising substantially the same variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) or functional fragment thereof.

A Vitaxin light chain polypeptide comprising substantially the same variable region amino acid sequence as that shown in FIG. 1B (SEQ ID NO:4) or a functional fragment thereof.

A LM609 grafted antibody exhibiting selective binding affinity to αvβ3 comprising at least one LM609 grafted heavy chain polypeptide comprising substantially the same variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) and at least one LM609 grafted light chain polypeptide comprising substantially the same variable region amino acid sequence as,.that shown in FIG. 7 (SEQ ID NO:32) or a functional fragment thereof.

A nucleic acid encoding a LM609 grafted heavy chain polypeptide comprising substantially the same LM609 grafted heavy chain variable region nucleotide sequences as that shown in FIG. 1A (SEQ ID NO:1) or a fragment thereof.

A nucleic acid encoding a LM609 grafted light chain polypeptide comprising substantially the same LM609 grafted light chain variable region nucleotide sequences as that shown in FIG. 7 (SEQ ID NO:31) or a fragment thereof.

A nucleic acid encoding a LM609 grafted antibody heavy chain polypeptide comprising a nucleotide sequence encoding substantially the same LM609 grafted heavy chain variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) or fragment thereof.

A nucleic acid encoding a LM609 grafted antibody light chain polypeptide comprising a nucleotide sequence encoding substantially the same LM609 grafted light chain variable region amino acid sequence as that shown in FIG. 7 (SEQ ID NO:32) or fragment thereof.

A LM609 grafted heavy chain polypeptide comprising substantially the same variable region amino acid sequence as that shown in FIG. 1A (SEQ ID NO:2) or functional fragment thereof.

A LM609 grafted light chain polypeptide comprising substantially the same variable region amino acid sequence as that shown in FIG. 7 (SEQ ID NO:32) or a functional fragment thereof.

A nucleic acid encoding a heavy chain polypeptide for monoclonal antibody LM609 comprising substantially the same heavy chain variable region nucleotide sequence as that shown in FIG. 2A (SEQ ID NO:5) or a fragment thereof.

A nucleic acid encoding a light chain polypeptide for monoclonal antibody LM609 comprising substantially the same light chain variable region nucleotide sequence as that shown in FIG. 2B (SEQ ID NO:7) or a fragment thereof.

A nucleic acid encoding a heavy chain polypeptide for monoclonal antibody LM609 comprising a nucleotide sequence encoding substantially the same heavy chain variable domain amino acid sequence of monoclonal antibody LM609 as that shown in FIG. 2A (SEQ ID NO:6) or fragment thereof.

A nucleic acid encoding a heavy chain polypeptide for monoclonal antibody LM609 comprising a nucleotide sequence encoding substantially the same light chain amino acid sequence of monoclonal antibody LM609 as that shown in FIG. 2B (SEQ ID NO:8) or fragment thereof.

A method of inhibiting a function of αvβ3 comprising contacting αvβ3 with Vitaxin or a functional fragment thereof under conditions which allow binding of Vitaxin to αvβ3.

A method of treating an αvβ3-mediated disease comprising administering an effective amount of Vitaxin or a functional fragment thereof under conditions which allow binding to αvβ3.

An enhanced LM609 grafted antibody exhibiting selective binding affinity to αvβ3 or a functional fragment thereof, comprising at least one amino acid substitution in one or more CDRs of a LM609 grafted heavy chain variable region polypeptide or a LM609 grafted light chain variable region polypeptide, wherein the αvβ3 binding affinity of said enhanced LM609 grafted antibody is maintained.

A high affinity LM609 grafted antibody exhibiting selective binding affinity to αvβ3, or a functional fragment thereof, comprising at least one amino acid substitution in one or more CDRs of a LM609 grafted heavy chain variable region polypeptide or a LM609 grafted light chain variable region polypeptide, wherein the αvβ3 binding affinity of said high affinity LM609 grafted antibody is enhanced.

A nucleic acid encoding an enhanced LM609 grafted antibody, or a functional fragment thereof, exhibiting selective binding affinity to αvβ3 comprising at least one amino acid substitution in one or more CDRs of a LM609 grafted heavy chain variable region polypeptide or a LM609 grafted light chain variable region polypeptide, wherein the αvβ3 binding affinity of said enhanced LM609 grafted antibody is maintained or enhanced.

A nucleic acid encoding a high affinity LM609 grafted antibody, or a functional fragment thereof, exhibiting selective binding affinity to αvβ3 comprising at least one amino acid substitution in one or more CDRs of a LM609 grafted heavy chain variable region polypeptide or a LM609 grafted light chain variable region polypeptide, wherein the αvβ3 binding affinity of said high affinity LM609 grafted antibody is enhanced.