Antigen binding protein against HER3
The invention provides an antigen-binding protein that specifically binds to a conformational epitope formed by domain III & IV of human epidermal growth factor receptor 3 (HER3) and antigen-binding proteins which compete therewith for binding, as well as fusion protein or conjugate comprising these. The invention also provides nucleic acid molecule comprising a sequence encoding said antigen binding proteins, vectors comprising the nucleic acid, and cells and pharmaceuticals comprising the antigen binding protein, the fusion protein, the nucleic acid, or the vector. The invention also provides the antigen binding protein, the fusion protein or conjugate, the nucleic acid, the vector, the cell, or the pharmaceutical for use as a medicament. The invention further provides a method of inhibiting tumor growth or treating cancer, comprising administering a therapeutically effective amount of the antigen binding protein, the fusion protein or conjugate, the nucleic acid, the vector, the cell, or the pharmaceutical.
1. An antigen binding protein comprising
(a) a CDRH1 comprising amino acids 32-37 according to SEQ ID NO: 2, a CDRH2 comprising amino acids 52-69 according to SEQ ID NO: 2, and a CDRH3 comprising amino acids 102-112 according to SEQ ID NO: 2, and
(b) a CDRL1 comprising amino acids 23-33 according to SEQ ID NO: 3, a CDRL2 comprising amino acids 49-55 according to SEQ ID NO: 3, and a CDRL3 comprising amino acids 88-98 according to SEQ ID NO: 3.
2. The antigen-binding protein of claim 1 , wherein the antigen-binding protein specifically binds to a conformational epitope formed by domain III and IV of human epidermal growth factor receptor 3 (HER3).
3. The antigen binding protein according to claim 2 , wherein the conformational epitope is formed by amino acids 329 to 531 of domain III of HER3 according to SEQ ID NO: 1 and by amino acids 532 to 587 of domain IV of HER3 according to SEQ ID NO: 1.
4. The antigen binding protein according to claim 2 , which:
(a) binds to HER3-expressing cells with an EC 50 value below 15 nM; and/or
(b) binds to a monomeric HER3 with a KD of below 100 nM; and/or
(c) inhibits heregulin-induced HER3 phosphorylation HER3 with an IC 50 value below 10 nM.
5. The antigen binding protein according to claim 2 , which inhibits (i) binding of HER3 to its ligand, (ii) receptor activation and/or signaling, (iii) induces HER3 internalization, (iv) inhibits cell proliferation, and/or (v) tumor growth.
6. The antigen-binding protein according to claim 1 , wherein the antigen binding protein is selected from the group consisting of
a) an antibody or an antigen-binding fragment thereof,
b) antibody-like protein, and
c) a peptidomimetic.
7. The antigen binding protein according to claim 1 , wherein the antigen-binding protein is monospecific, bispecific or multispecific.
8. A fusion protein comprising the antigen-binding protein according to claim 1 , further comprising at least one pharmaceutically active moiety.
9. A nucleic acid encoding the antigen binding protein according to claim 1 , or the fusion protein according to claim 8 .
10. A recombinant vector comprising the nucleic acid of claim 9 .
11. A recombinant host cell comprising the nucleic acid of claim 9 .
12. A pharmaceutical composition comprising the antigen binding protein according to claim 1 , and further comprising one or more pharmaceutically acceptable carriers, diluents, excipients, fillers, binders, lubricants, glidants, disintegrants, adsorbents, and/or preservatives.
13. A method comprising administering the antigen binding protein according to claim 1 to a subject.
14. A method of inhibiting HER3-positive tumor growth or treating HER3-positive cancer, comprising administering to a patient in need thereof a therapeutically effective amount of the antigen binding protein according to claim 1 to inhibit HER3-positive tumor growth or treat HER3-positive cancer.