Neovascular-targeted immunoconjugates
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Abstract
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.
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Citations
46 Claims
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1-20. -20. (canceled)
- 21. A method for treating a disease associated with neovascularization, which comprises administering to a patient having the disease an effective amount of an immunoconjugate protein having an effector domain which can induce a cytolytic immune response against a targeted cell, conjugated to a targeting domain comprising a mutant form of factor VII that binds to tissue factor and has reduced blood clotting activity relative to wild-type factor VII.
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29. A method for treating cancer in a patient, which comprises administering to the patient an effective amount of an immunoconjugate protein comprising the Fc region of a human IgG1 immunoglobulin conjugated to a targeting domain comprising a mutant form of human factor VII having a substitution selected from the group consisting of:
- a substitution of alanine for lysine-341;
a substitution of alanine for serine-344; and
a substitution of alanine for lysine-341 and for serine-344. - View Dependent Claims (30, 31, 36, 41, 42, 43)
- a substitution of alanine for lysine-341;
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32. A method for treating macular degeneration in a patient, which comprises administering to the patient an effective amount of an immunoconjugate protein comprising the Fc region of a human IgG1 immunoglobulin conjugated to a targeting domain comprising a mutant form of human factor VII having a substitution selected from the group consisting of:
- a substitution of alanine for lysine-341;
a substitution of alanine for serine-344; and
a substitution of alanine for lysine-341 and for serine-344. - View Dependent Claims (33, 34, 37, 44, 45, 46)
- a substitution of alanine for lysine-341;
Specification