NOVEL ANTI-IGF-IR ANTIBODIES AND USES THEREOF

摘要

Isolated antibody (Ab) and its functional fragments, able to bind to the human receptor for insulin-like growth factor I (IGF-1R) and/or to inhibit specifically the tyrosine kinase activity of IGF-IR are new. Ab inhibits natural binding of the ligand (IGF1) to IGF-1R with IC50 less than 0.3, preferably 0.03, nM and also inhibits binding of IGF2 to the same receptor with IC50 less than 0.1, preferably 0.1, nM. Independent claims are also included for the following: (1) murine hybridoma that secretes Ab; (2) antibodies, and their fragments, produced by the hybridomas of (1); (3) isolated nucleic acid (NA) that is (a) DNA or RNA encoding Ab or its functional fragments; (b) complements of (a); (c) fragments of at least 18 nucleotides (nt) that hybridize under highly stringent conditions to any of Seq. (9)-(14) (reproduced) or with sequences having at least 80% identify after optimal alignment; or (d) fragments of at least 18 nt that hybridize under highly stringent conditions to light/heavy chain encoding sequences (Seq. (15) and (16)) or with sequences having at least 80% identity; (4) vector that contains NA; (5) host cell that contains the vector of (4); (6) non-human transgenic animal containing a cell transformed by the vector of (4); (7) method for producing Ab or its functional fragments; (8) in vitro diagnosis of diseases caused by under- or over-expression of IGF-1R by treating a test sample with optionally labeled Ab; (9) kit for method (8); (10) in vitro method for identifying a modulator of IGF-1R; (11) method for detecting a binding partner of Ab; and (12) method for purifying IGF-1R. ACTIVITY : Cytostatic; Antipsoriatic; Antiarteriosclerotic. Antibodies from hybridoma I-3499 were tested against the androgen-dependent prostate cancer DU145, injected subcutaneously into athymic, nude, female mice. The antibody was given in 0.2 mg doses 24 hours after cell implantation, then twice weekly. Tumor volumes were 60 and 130 mm 3> after 12 and 20 days, in untreated controls, but only 15 and 35 mm 3> in treated animals. MECHANISM OF ACTION : Modulating activity, especially tyrosine kinase activity, of insulin-like growth factor receptor.