Neovascular-targeted immunoconjugates
Immunoconjugates for treating diseases associated with neovascularization such as cancer, rheumatoid arthritis, the exudative form of macular degeneration, and atherosclerosis are described. The immunoconjugates typically consist of the Fc region of a human IgG1 immunoglobulin including the hinge, or other effector domain or domains that can elicit, when administered to a patient, a cytolytic immune response or cytotoxic effect against a targeted cell. The effector domain is conjugated to a targeting domain which comprises a factor VII mutant that binds with high affinity and specificity to tissue factor but does not initiate blood clotting such as factor VII having a substitution of alanine for lysine-341 or of alanine for serine-344.
1. A method for inhibiting neovascularization in the eye of a patient having wet form of macular degeneration, which comprises administering to the patient a conjugate protein having as an effector domain a human IgG1 immunoglobulin Fc domain, said effector domain conjugated to a targeting domain comprising a mutant form of human factor VII comprising the amino acid sequence encoded by the nucleotide sequence at positions 202-1419 of SEQ ID NO: 12, wherein neovascularization in the eye is inhibited.
2. A method for inhibiting neovascularization that occurs in the eye of a patient having wet form of macular degeneration, which comprises administering to the patient an immunoconjugate protein comprising the Fc domain of a human IgG1 immunoglobulin conjugated to a targeting domain comprising a mutant form of human factor VII comprising the amino acid sequence encoded by the nucleotide sequence at positions 202-1419 of SEQ ID NO: 12.