Anti-ErbB3 antibodies
Monoclonal antibodies that bind and inhibit activation of epidermal growth factor receptor related member ErbB3/HER3 are disclosed. The antibodies can be used to treat cell proliferative diseases and disorders, including certain forms of cancer, associated with activation of ErbB3/HER3.
1. An isolated antibody that binds human ErbB3 comprising
(i) an immunoglobulin heavy chain variable region comprising a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 57 and SEQ ID NO: 75, a CDR H2 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 58 and SEQ ID NO: 148, and a CDR H3 comprising the amino acid sequence of SEQ ID NO: 59; and
(ii) an immunoglobulin light chain variable region comprising a CDR L1 comprising the amino acid sequence of SEQ ID NO: 60, a CDR L2 comprising the amino acid sequence of SEQ ID NO: 61, and a CDR L3 comprising the amino acid sequence of SEQ ID NO: 62.
2. The antibody of claim 1 , wherein the immunoglobulin heavy chain variable region comprises a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 57 and SEQ ID NO: 75, a CDR H2 comprising the amino acid sequence of SEQ ID NO: 148, and a CDR H3 comprising the amino acid sequence of SEQ ID NO: 59; and
wherein the immunoglobulin light chain variable region comprises a CDR L1 comprising the amino acid sequence of SEQ ID NO: 60, a CDR L2 comprising the amino acid sequence of SEQ ID NO: 61, and a CDR L3 comprising the amino acid sequence of SEQ ID NO: 62.
3. The antibody of claim 1 , wherein the CDR sequences are interposed between human or humanized framework sequences.
4. The antibody of claim 2 , wherein the immunoglobulin heavy chain variable region and the immunoglobulin light chain variable region are selected from the group consisting of:
(a) an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 154 and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 168 and
(b) an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 154 and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 166.
5. The antibody of claim 4 , wherein the immunoglobulin heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 154 and the immunoglobulin light chain variable region comprises the amino acid sequence of SEQ ID NO: 168.
6. The antibody of claim 2 , wherein the antibody comprises an immunoglobulin heavy chain and an immunoglobulin light chain selected from the group consisting of:
(a) an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 190 and an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 206; and
(b) an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 190 and an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 204.
7. The antibody of claim 6 , wherein the immunoglobulin heavy chain comprises the amino acid sequence of SEQ ID NO: 190 and the immunoglobulin light chain comprises the amino acid sequence of SEQ ID NO: 206.
8. The antibody of claim 4 or 6 , wherein the antibody is a monoclonal antibody or an antigen binding fragment thereof.
9. The antibody of claim 1 , wherein the antibody has a K D of 200 pM or lower as measured by surface plasmon resonance.
10. The antibody of claim 1 , wherein the immunoglobulin heavy chain variable region comprises a CDR H1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 57 and SEQ ID NO: 75, a CDR H2 comprising the amino acid sequence of SEQ ID NO: 58, and a CDR H3 comprising the amino acid sequence of SEQ ID NO: 59; and
wherein the immunoglobulin light chain variable region comprises a CDR L1 comprising the amino acid sequence of SEQ ID NO: 60, a CDR L2 comprising the amino acid sequence of SEQ ID NO: 61, and a CDR L3 comprising the amino acid sequence of SEQ ID NO: 62.
11. The antibody of claim 10 , wherein the immunoglobulin heavy chain variable region and the immunoglobulin light chain variable region are selected from the group consisting of:
(a) an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 152 and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 168 and
(b) an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 152 and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 166.
12. The antibody of claim 10 , wherein the antibody comprises an immunoglobulin heavy chain and an immunoglobulin light chain selected from the group consisting of:
(a) an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 188 and an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 206 and
(b) an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 188 and an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 204.