Monoclonal antibody that binds human notch2 and notch3
The present invention relates to Notch-binding agents and Notch antagonists and methods of using the agents and/or antagonists for treating diseases such as cancer. The present invention provides antibodies that specifically bind to a non-ligand binding region of the extracellular domain of one or more human Notch receptor, such as Notch2 and/or Notch3, and inhibit tumor growth. The present invention further provides methods of treating cancer, the methods comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.
1. An isolated monoclonal antibody that specifically binds epidermal growth factor (EGF) repeat 10 of human NOTCH2 and EGF repeat 9 of human NOTCH3.
2. The antibody of claim 1 , which binds at least part of the sequence HKGAL (SEQ ID NO:28) within EGF repeat 10 of human NOTCH2.
3. The antibody of claim 2 , which binds at least part of the sequence HEDAI (SEQ ID NO:29) within EGF repeat 9 of human NOTCH3.
4. The antibody of claim 1 , which binds at least part of the sequence HEDAI (SEQ ID NO:29) within EGF repeat 9 of human NOTCH3.
5. The antibody of claim 1 , which binds human NOTCH2 with a K D of about 1 nM or less.
6. The antibody of claim 5 , which binds human NOTCH3 with a K D of about 1 nM or less.
7. The antibody of claim 1 , which binds human NOTCH3 with a K D of about 1 nM or less.
8. The antibody of claim 1 , which is a recombinant antibody, a chimeric antibody, a humanized antibody, a human antibody, a bispecific antibody, a monospecific antibody, an antibody fragment, an IgG1 antibody, or an IgG2 antibody.
9. The antibody of claim 8 , which is a human antibody.
10. The antibody of claim 8 , which is a humanized antibody.
11. The antibody of claim 8 , which is an IgG1 antibody.
12. The antibody of claim 8 , which is an IgG2 antibody.
13. The antibody of claim 1 , which is an antagonist of human NOTCH2 and/or human NOTCH3.
14. The antibody of claim 1 , which inhibits binding of a ligand to human NOTCH2 and/or human NOTCH3.
15. The antibody of claim 1 , which inhibits human NOTCH2 and/or human NOTCH3 signaling.
16. The antibody of claim 1 , which inhibits tumor growth.