MÉTODOS PARA TRATAMENTO E/OU PREVENÇÃO DE UMA DOENÇA E DE UMA ALTERAÇÃO, MÉTODO PARA A INIBIÇÃO E/OU A PREVENÇÃO DO CRESCIMENTO DE CÉLULAS DE TUMOR NO OSSO E SINTOMAS RELACIONADOS COM O MESMO, POLIPEPTÍDEO SELETIVO PARA INTEGRINA ANB3, COMPOSIÇÃO FISIOLOGICAMENTE ACEITÁVEL, POLIPEPTÍDEO, MÉTODO PARA PREPARAR UM POLIPEPTÍDEO, E, POLINUCLEOTÍDEO

摘要

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin ±v²3 receptor-antagonist activity and substantially reduced integrin ±IIb²3 and/or ±5²1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin ±IIb²3 and/or ±5²1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of ±v²3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.