Patent FR-2873699-A1 (FR)
Title: New isolated antibody or its functional fragments that binds to human insulin-like growth factor I receptor and inhibits tyrosine kinase activity, for treating cancer, psoriasis or atherosclerosis
Inventor: GOETSCH LILIANE
IPC: A61P17/06
Filed: 2004-07-29
Abstract: An isolated antibody (I), or one of its functional fragments, being capable of binding to the human insulin-like growth factor I receptor (IGF-IR) and, if necessary, inhibiting the natural attachment of its ligands IGF1 and/or IGF2, and/or capable of specifically inhibiting the tyrosine kinase activity of IGF-IR, is new. An isolated antibody (I), or one of its functional fragments, being capable of binding to the human insulin-like growth factor I receptor (IGF-IR) and, if necessary, inhibiting the natural attachment of its ligands IGF1 and/or IGF2 and/or capable of specifically inhibiting the tyrosine kinase activity of IGF-IR, comprises: (i) a light chain comprising at least one complementary determining region (CDR) chosen from: (a) Arg-Ser-Ser-Gln-Thr-Ile-Ile-His-Ser-Asn-Gly-Asn-Thr-Tyr-Leu-Glu (SEQ ID No: 1), Lys-Val-Ser-Asn-Arg-Phe-Ser (SEQ ID No: 2) or Phe-Gln-Gly-Ser-His-Val-Pro-Tyr-Thr-Phe (SEQ ID No: 3); (b) Lys-Ala-Ser-Gln-Asn-Val-Val-Thr-Asn-Val-Ala (SEQ ID No: 7), Ser-Ala-Ser-Tyr-Arg-Tyr-Ser (SEQ ID No: 8) or His-Gln-Tyr-Asn-Asn-Phe-Pro-Leu-Thr (SEQ ID No: 9); and (c) Ile-Thr-Ser-Thr-Asp-Ile-Asp-Asp-Asp-Met-Asn (SEQ ID No: 13), Glu-Gly-Asn-Thr-Leu-Arg-Pro (SEQ ID No: 14) or Leu-Gln-Ser-Asp-Lys-Met-Pro-Leu-Thr (SEQ ID No: 15), or at least one CDR having a sequence at least 80% identity after optimum alignment with any one of the sequences from SEQ ID No: 1-3, 7-9 or 13-15; or (ii) a heavy chain comprising at least one CDR chosen from: (a') Asp-Tyr-Trp-Met-Asn (SEQ ID No: 4), Leu-Ile-His-Pro-Ser-Asp-Ser-Glu-Thr-Arg-Leu-Asp-Gln-Asn-Phe-Tyr (SEQ ID No: 5) or Ser-Val-Ile-Tyr-Tyr-Gly-Asn-Tyr-Arg-Trp-Tyr-Phe-Asp (SEQ ID No: 6); (b') Glu-Tyr-Gly-Val-Ser (SEQ ID No: 10), Val-Ile-Trp-Gly-Gly-Arg-Asp-Thr-Tyr-Tyr-His-Ser-Pro-Leu-Lys-Ser (SEQ ID No: 11) or His-Glu-Gly-Met-Asp-Tyr (SEQ ID No: 12); and (c') Asn-Tyr-Ala-Met-Ser (SEQ ID No: 16), Ser-Ile-Gly-Ser-Ala-Gly-Tyr-Ile-His-Tyr-Pro-Asp-Ser-Val-Lys-Gly (SEQ ID No: 17) or Glu-Gly-Gly-Leu-Val-Trp-Phe-Ala-Tyr (SEQ ID No: 18), or at least one CDR having at least 80% identity after optimum alignment with any one of the sequences from SEQ ID No: 4-6, 10-12 or 16-18. Independent claims are also included for the following: (1) a murine hybridoma (II) capable of secreting (I), and deposited at the CNCM under the number I-3249; (2) an antibody (III) or one of its functional fragments, being secreted by (II); and (3) a composition (IV) comprising (I) or (III). ACTIVITY : Cytostatic; Antipsoriatic; Antiarteriosclerotic. Two million DU145 cells in phosphate buffered saline were engrafted to Swiss nude mice. Test mice were treated subcutaneously with 200 mu g of 13F5 antibody (anti-IGF-1R antibody). The control group was treated with a murine isotype control (EC2) and the tumor volume was measured once a week. The results showed that the 13F5 antibody significantly inhibited the in vivo growth of DU145 cells compared to control group. MECHANISM OF ACTION : Inhibitor of tyrosine kinase activity of IGF-IR; Inhibitor of binding of ligands to IGF-IR.