Patent EA-002353-B1 (EA)
Title: Leptin as an inhibitor of tumor cell proliferation
Inventor: BARKAN DALIT
IPC: A61K38/22
Filed: 1998-04-26
Abstract: 1. The use of an active agent selected from the group consisting of leptin, leptin fusion proteins, leptin muteins, leptin receptor agonists, active fragments or fractions of any one thereof, as an inhibitor of tumor cell proliferation. 2. The use of an active agent according to claim 1 as an inhibitor of cell proliferation for the treatment of malignancies in mammals. 3. The use of an active agent according to claim 1 or claim 2 as an inhibitor of growth-factor dependent tumors. 4. The use of an active agent according to any one of claims 1-3, as an inhibitor of human breast carcinoma cell proliferation. 5. The use of an active agent according to claim 1 or claim 3 as an inhibitor of the growth stimulatory effect of insulin on tumor cells, as mediated, at least partially, by the insulin receptor substrate-l (IRS-1)/growth factor receptor-associated binding protein-2 (GRB2) pathway. 6. The use of an active agent according to claim 1 or claim 3 as an inhibitor of the mitogenic responses in tumor cells to one or more receptor kinases, growth factors and cytokines of the group consisting of IGF-1, IL-4 and IL-9, for all of which IRS-1 is a substrate, for the treatment of tumors. 7. The use of an active agent according to any one of claims 1-6 as an inhibitor of basal and insulin-induced tumor cell proliferation for the treatment of human breast cancers. 8. The use of an active agent according to any one of claims 1-7, wherein said active ingredient is leptin. 9. The use of an active agent selected from the group consisting of leptin, leptin fusion proteins, leptin muteins, leptin receptor agonists, active fragments or fractions of any one thereof, active analogs or derivatives of any one thereof, salts of any one thereof, and mixtures of any thereof, for use in the preparation of a medicament for the inhibition of tumor cell proliferation. 10. The use according to claim 9 as an inhibitor of cell proliferation for the treatment of malignancies in mammals. 11. The use according to claim 9 or claim 10 as an inhibitor of growth-factor dependent tumors. 12. The use according to any one of claims 9-11, as an inhibitor of human breast carcinoma cell proliferation. 13. The use according to any of claims 9-12 for the inhibition of the growth stimulatory effect of insulin on tumor cells, as mediated, at least partially, by the IRS-1/GRB2 pathway. 14. The use according to 9 or 11 22 wherein the growth factor is selected from the group consisting of receptor kinases, growth factors and cytokines (IGF-1, IL-4 and IL-9) for all of which IRS-1 is a substrate. 15. The use according to any of claims 9-14 for the inhibition of basal and insulin-induced tumor cell proliferation, for the treatment of human breast cancers. 16. The use according to any one of claims 9-15, wherein said active agent is leptin. 17. A pharmaceutical composition for the inhibition of tumor cell proliferation comprising a agent as an active ingredient selected from the group consisting of leptin, leptin fusion proteins, leptin muteins, leptin receptor agonists, active fragments or fractions of any one thereof, and any mixtures thereof, and a pharmaceutical carrier, diluent or excipient. 18. The use of a pharmaceutical composition according to claim 17 for the treatment of malignancies in mammals. 19 The use of apharmaceutical composition according to claim 17 for the inhibition of growth-factor-dependent tumors. 20. The use of a pharmaceutical composition according to claim 17 for the inhibition of human breast carcinoma cell proliferation. 21. The use of a pharmaceutical composition according to claim 17 for treatment of human breast carcinoma. 22. The use according to claim 19 for the inhibition of the growth stimulatory effect of insulin on tumor cells, as mediated, at least partially, by the IRS- 1/GRB2 pathway. 23. The use according to claim 19 or claim 22 wherein the growth factor is selected from the group consisting of receptor kinases, growth factors and cytokines (IGF-1, IL-4 and IL-9) for all of which IRS-1 is a substrate. 24. The use according to any one of claims 17-23, wherein said active agent is leptin. 25. A method for treating tumors comprising administering to a patient a pharmaceutical composition according to claim 17 in a suitable dosage form and by a suitable route of administration. 26. A method for inhibiting tumor cell proliferation in mammals comprising administering to a patient a pharmaceutical composition according to claim 17 in a suitable dosage form and by a suitable route of administration.