Bi-specific antigen-binding polypeptides
The present invention provides antigen-binding polypeptides (e.g., bi-specific antigen-binding polypeptides) that specifically bind to a first and a second target antigen with high affinity. The present invention also provides novel antigen-binding polypeptides that specifically bind to HER2 and antagonize HER2 activation. The invention also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen binding polypeptides. Methods of using antigen-binding polypeptide of the invention to treat disease (e.g., cancer) are also encompassed by the invention.
1. An isolated antigen-binding polypeptide that specifically binds to human HER2, comprising a VH domain comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 15, and 16.
2. A pharmaceutical composition comprising the antigen-binding polypeptide of claim 1 and a pharmaceutically acceptable carrier.
3. An isolated bi-specific antigen-binding polypeptide that is capable of binding to human PDGFRβ and human HER2, comprising an antibody heavy chain comprising a first VH domain that specifically binds to human PDGFRβ, C-terminally linked to a second VH domain that specifically binds to human HER2,
wherein the first VH domain comprises the amino acid set forth in SEQ ID NO: 24, and
wherein the second VH domain comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 13-16.
4. The antigen-binding polypeptide of claim 3 , wherein the antibody heavy chain is genetically linked to the second VH domain through an amino acid linker.
5. The antigen-binding polypeptide of claim 4 , wherein the linker comprises the amino acid sequence set forth in SEQ ID NO: 23.
6. The antigen-binding polypeptide of claim 3 , further comprising an antibody light chain, the light chain comprising a VL domain that specifically binds to an antigen, wherein the heavy and light chains are naturally paired.
7. An antigen-binding polypeptide comprising a dimer of two antigen-binding polypeptides of claim 3 .
8. The antigen-binding polypeptide of claim 6 , wherein the VL domain comprises the amino acid sequence set forth in SEQ ID NO: 28.
9. A pharmaceutical composition comprising the antigen-binding polypeptide of claim 3 and a pharmaceutically acceptable carrier.