Antibodies against platelet-derived growth factor (PDGF)
Binding proteins that bind one or more of VEGF, PDGF and/or their receptors, including antibodies, CDR-grafted antibodies, humanized antibodies, binding fragments, fusion proteins, and bispecific or multispecific proteins thereof are disclosed. Also disclosed are methods of making and using the binding proteins.
1. An antibody or antigen binding fragment thereof capable of binding platelet-derived growth factor (PDGF), wherein the antibody or antigen binding fragment comprises
CDRs 1-3 from SEQ ID NO: 15 and CDRs-1-3 from SEQ ID NO: 16.
2. The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment comprises
SEQ ID NO: 15 and SEQ ID NO: 16.
3. The antibody or antigen binding fragment of claim 1 , further comprising heavy and light chain constant domains selected from Table 3.
4. The antibody or antigen binding fragment of claim 1 , further comprising:
a) a heavy chain constant region on the first polypeptide chain comprising a human IgG1 heavy chain sequence modified by substitution of leucines at positions 234 and 235 with alanines, and optionally also comprises a substitution of histidine at position 435 with alanine, wherein the amino acid positions are numbered using EU index numbering; and
(b) a light chain constant region on the second polypeptide chain comprising a human kappa light chain constant region sequence.
5. An antibody or antigen binding fragment that competes with the antibody or antigen binding fragment of claim 1 for binding to PDGF.
6. An antibody or antigen binding fragment that binds to the same epitope of PDGF as the antibody or antigen binding fragment of claim 1 .
7. An antibody conjugate comprising the antibody or antigen binding fragment of claim 1 , the antibody conjugate further comprising an immunoadhesion molecule, an imaging agent, a therapeutic agent, or a cytotoxic agent, wherein the imaging agent is a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, or biotin, wherein the radiolabel is 3 H, 14 C, 35 S, 90 Y, 99 Tc, 111 In, 125 I, 131 I, 177 Lu, 166 Ho, or 153 Sm, and wherein the therapeutic or cytotoxic agent is an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, or an apoptotic agent.
8. A pharmaceutical composition comprising the antibody or antigen binding fragment of claim 1 , and a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , further comprising at least one additional therapeutic agent.