Angiopoietin 2, VEGF dual antagonists
The present disclosure relates to chimeric molecules which are fusion proteins comprising two components: an Ang-2 binding peptide linked to either a VEGF antibody or a VEGF receptor-Fc fusion protein. The Ang2 peptide, VEGF antibody, and VEGF receptor-Fc fusion proteins are each defined below with reference to percent identity to a reference sequence. The chimeric molecule is a fusion protein, dual antagonist of Ang2 and VEGF for treatment of cancers, proliferative retinopathies, neovascular glaucoma, macular edema, AMD, and rheumatoid arthritis.
1. A chimeric molecule which comprises an Ang2 binding peptide and an antibody which binds to VEGF, comprising:
a. a light chain comprising the amino acid sequence of SEQ ID NO: 3; and
b. a peptide-heavy chain fusion molecule comprising the amino acid sequence of SEQ ID NO:15 or SEQ ID NO:16.
2. A chimeric molecule which comprises an Ang2 binding peptide and an antibody which binds to VEGF,
wherein the Ang2 binding peptide is fused to the N-terminus of the light chain and wherein the fusion molecule comprises the amino acid sequence of SEQ ID NO: 14 and
wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO: 2.
3. A pharmaceutical composition comprising a chimeric molecule of claim 1 and a pharmaceutically acceptable carrier.
4. A chimeric molecule, which comprises an antibody and an Ang2 binding peptide, wherein the antibody comprises a light chain and a heavy chain,
wherein the light chain comprises the amino acid of SEQ ID NO: 3,
wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2,
wherein said peptide is fused to the C-terminus of the heavy chains of said antibody, optionally with a peptide linker,
wherein the Ang2 binding peptide consisting of the amino acid sequence of SEQ ID NO:9, and wherein said antibody binds to VEGF.
5. A pharmaceutical composition comprising the chimeric molecule of claim 4 and a pharmaceutically acceptable carrier.
6. A chimeric molecule, which comprises an antibody and an Ang2 binding peptide, wherein the antibody comprises a light chain and a heavy chain,
wherein the light chain comprises the amino acid of SEQ ID NO: 3,
wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2,
wherein the peptide is fused to the C-terminus of the heavy chains of the antibody, optionally with a peptide linker,
wherein the peptide consisting of the amino acid sequence of SEQ ID NO: 12, and
wherein said antibody binds to VEGF.
7. A pharmaceutical composition comprising the chimeric molecule of claim 6 and a pharmaceutically acceptable carrier.