Human C-FMS antigen binding proteins
Antigen binding proteins that bind to human c-fms protein are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of c-fms to CSF-1, reduce monocyte migration into tumors, and reduce the accumulation of tumor-associated macrophages.
1. An isolated antibody or fragment thereof that binds human c-fms, wherein the antibody or fragment comprises:
(A) a heavy chain variable domain comprising a CDRH1, a CDRH2 and a CDRH3, wherein the CDRH1 comprises the amino acid sequence of SEQ ID NO:147, the CDRH2 comprises the amino acid sequence of SEQ ID NO:163, and the CDRH3 comprises the amino acid sequence of SEQ ID NO:186; and
(B) a light chain variable domain comprising a CDRL1, a CDRL2 and a CDRL3, wherein the CDRL1 comprises the amino acid sequence of SEQ ID NO:193; the CDRL2 comprises the amino acid sequence of SEQ ID NO:214 and the CDRL3 comprises the amino acid sequence of SEQ ID NO:228.
2. The antibody or fragment of claim 1 that has one or more of the following characteristics:
(A) is a monoclonal antibody;
(B) is a chimeric, a humanized or a fully human antibody;
(C) is an antibody of the IgG1-, IgG2-, IgG3- or IgG4-type;
(D) is a Fab fragment, a Fab′ fragment, an F(ab′)2 fragment, or an Fv fragment;
(E) is labeled.
3. An isolated antibody or fragment thereof that binds human c-fms, wherein the antibody or fragment comprises:
(A) a heavy chain variable domain comprising the amino sequence of SEQ ID NO:77; and
(B) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:110.
4. The antibody or fragment thereof of claim 3 that has one or more of the following characteristics:
(A) is a monoclonal antibody;
(B) is a chimeric, a humanized or a fully human antibody;
(C) is an antibody of the IgG1-, IgG2-, IgG3- or IgG4-type;
(D) is a Fab fragment, a Fab′ fragment, an F(ab′)2 fragment, or an Fv fragment;
(E) is labeled.
5. An isolated, fully human, monoclonal antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:11 and the light chain comprises the amino acid sequence of SEQ ID NO:44.
6. An isolated antibody or antibody fragment that competes with the antibody or fragment of claim 3 for binding to the extracellular domain of human c-fms of SEQ ID NO:1.
7. A composition comprising the antibody or fragment of claim 1 and a pharmaceutically acceptable diluent or carrier.
8. A composition comprising the antibody or fragment of claim 3 and a pharmaceutically acceptable diluent or carrier.
9. A composition comprising the antibody of claim 5 and a pharmaceutically acceptable diluent or carrier.
10. A composition comprising the antibody or fragment of claim 6 and a pharmaceutically acceptable diluent or carrier.