COMPOSITIONS FOR TREATING A DISEASE OR CONDITION ASSOCIATED WITH ABNORMAL ANGIOGENESIS

摘要

The present invention provides methods of treating (including preventing) a disease or condition associated with abnormal angiogenesis in a subject include administering a therapeutically effective amount of an AA targeting compound of the invention to the subject. The AA targeting compounds comprise AA targeting agent-linker conjugates which are linked to a combining site of an antibody.

主权项

1. A compound of the formula:
R1-[AA targeting agent]-R2 wherein R1 is CH3, C(O)CH3, C(O)CH3, C(O)CH2CH3, C(O)CH2CH2CH3, C(O)CH(CH3)CH3, C(O)CH2CH2CH2CH3, C(O)CH(CH3)CH2CH3, C(O)C6H5, C(O)CH2CH2(CH2CH2O)1-5Me, dichlorobenzoyl (DCB), difluorobenzoyl (DFB), pyridinyl carboxlate (PyC) or amido-2-PEG, an amino protecting group, a lipid fatty acid group or a carbohydrate; and R2 is OH, NH2, NH(CH3), NHCH2CH3, NHCH2CH2CH3, NHCH(CH3)CH3, NHCH2CH2CH2CH3, NHCH(CH3)CH2CH3, NHC6H5, NHCH2CH2OCH3, NHOCH3, NHOCH2CH3, a carboxy protecting group, a lipid fatty acid group or a carbohydrate, and wherein [AA targeting agent] comprises a peptide of the sequence:(SEQ ID NO: 193)R1-Q1x2Y3Q4x5L6D7x8x9D10x11x12x13x14x15x16F17x18x19Q20Q21G22-R2 wherein one of Q1, x8, x9, x11, x12, x15, x16, x18, x19 or G22 is a linking residue comprising a nucleophilic side chain covalently linkable to the combining site of an antibody directly or via an intermediate linker, the linking residue being selected from the group comprising K, R, Y, C, T, S, homologs of lysine, homocysteine, homoserine, Dap, and Dab, or the N-terminus or C-terminus, and x2 is selected from the group consisting of K, N, R, H, AcK, Nick, CbcK and the linking residue, and x5 is selected from the group consisting of P, hP, dhP, or BnHP, and x9 is selected from the group consisting of L, I, ThA, AcK and the linking residue, and x8 is selected from the group consisting of E and the linking residue, and x11 is selected from the group consisting of Q, N, C, K, AcK, Dab, Dap and the linking residue, and x12 is selected from the group consisting of L, HL, Nva, I, HchA, HF, ThA, and x13 is selected from the group consisting of L, HL, Nva, I, HchA, HF, ThA, and x14 is selected from the group consisting of aromatic residues and the linking residue, and x15 is selected from the group consisting of D and the linking residue, and x16 is selected from the group consisting of Q, N and the linking residue, and x18 is selected from the group consisting of M and the linking residue, and. x19 is selected from the group consisting of L, I and the linking residue.