Uses of myostatin antagonists, combinations containing them and uses thereof

Abstract

The present invention relates to myostatin antagonists, for the treatment of cancer cachexia, and cancer cachexia due to chemotherapeutic treatment Especially, the myostatin antagonist bimagrumab was found to be beneficial in the treatment of cancer cachexia by reducing body weight loss. The present invention also relates to combinations and uses of a myostatin antagonist and an mTOR inhibitor for treating cancer cachexia by reducing, maintaining or increasing body weight loss or for use in treating age-related conditions.

1 . A combination comprising (a) ActRII receptor inhibitor and b) a chemotherapeutic agent. 
     
     
         2 . A combination according to  claim 1  for simultaneous, separate or sequential use. 
     
     
         3 . A combination according to  claim 1  or  2 , wherein the a) ActRII receptor inhibitor, and b) a chemotherapeutic agent are in separate form. 
     
     
         4 . A combination according to  claim 1 - 3  wherein a) is an anti-ActRII receptor antibody. 
     
     
         5 . A combination according to  claims 1 - 4  wherein said anti-ActRII antibody is bimagrumab 
     
     
         6 . A combination according to  claims 1 - 5  wherein b) is a platinum-containing anti-cancer agent. 
     
     
         7 . A combination according to any of the preceding claims for use as a medicament. 
     
     
         8 . A combination according to  claim 1 - 6  comprising (a) ActRII receptor inhibitor and b) a chemotherapeutic agent for use in the treatment of cancer cachexia. 
     
     
         9 . A combination according for use according to  claim 8  wherein the treatment of cancer cachexia is reduction of body weight loss. 
     
     
         10 . An ActRII receptor inhibitor for use in treating cancer cachexia. 
     
     
         11 . An ActRII receptor inhibitor for use according to  claim 10 , wherein cancer cachexia is due to treatment with a chemotherapeutic agent. 
     
     
         12 . An ActRII receptor inhibitor for use according to any  claim 10 - 11 , wherein the wherein treating cancer cachexia is reducing body weight loss. 
     
     
         13 . An ActRII receptor inhibitor for use according to  claims 10 - 12  in delaying time to progression of cancer in a patient. 
     
     
         14 . An ActRII receptor inhibitor for use according to  claims 10 - 12  in delaying time to progression of cancer cachexia. 
     
     
         15 . An ActRII receptor inhibitor for use according to  claims 10 - 12  in prolonging cancer survival. 
     
     
         16 . An ActRII receptor inhibitor for use according to  claims 10 - 15 , wherein the ActRII receptor inhibitor is an anti-ActRII receptor antibody. 
     
     
         17 . An ActRII receptor inhibitor for use according to  claim 16  wherein the anti-ActRII receptor antibody is bimagrumab 
     
     
         18 . An ActRII receptor inhibitor for use according to  claims 11 - 17 , wherein the chemotherapeutic agent is a platinum-containing anti-cancer agent. 
     
     
         19 . A combination comprising a) a myostatin antagonist and b) an mTOR inhibitor. 
     
     
         20 . A combination according to  claim 19  wherein the myostatin antagonist is an ActRII receptor inhibitor 
     
     
         21 . A combination according to  claim 20  wherein the ActRII receptor inhibitor is an anti-ActRII receptor antibody. 
     
     
         22 . A combination according to  claim 21  wherein the anti-ActRII receptor antibody is bimagrumab. 
     
     
         23 . A combination according to  claim 19 - 22  wherein the mTOR inhibitor is everolimus. 
     
     
         24 . A combination according to  claims 19 - 23  for use as a medicament. 
     
     
         25 . A combination according to  claims 19 - 23  for use in treating cancer cachexia. 
     
     
         26 . A combination according to  claims 19 - 23  wherein treating cancer cachexia is preventing body weight loss. 
     
     
         27 . A combination according to  claims 19 - 23  wherein treating cancer cachexia is maintaining body weight. 
     
     
         28 . A combination according to  claims 19 - 23  wherein treating cancer cachexia is increasing body weight. 
     
     
         29 . A combination according to  claims 1 - 9  or for use according to  claims 19 - 28  wherein the agents are in separate pharmaceutical compositions. 
     
     
         30 . A combination according to any one of  claims 19 - 23  for use in the treatment of an age related condition. 
     
     
         31 . A combination of  claim 30 , wherein the age related condition is selected from the group consisting of sarcopenia, skin atrophy, muscle wasting, brain atrophy, atherosclerosis, arteriosclerosis, pulmonary emphysema, osteoporosis, osteoarthritis, high blood pressure, erectile dysfunction, dementia, Huntington's disease, Alzheimer's disease, cataracts, age-related macular degeneration, prostate cancer, stroke, diminished life expectancy, impaired kidney function, and age-related hearing loss, aging-related mobility disability (e.g., frailty), cognitive decline, age related dementia, memory impairment, tendon stiffness, heart dysfunction such as cardiac hypertrophy and systolic and diastolic dysfunction, immunosenescence, cancer, obesity, and diabetes. 
     
     
         32 . A myostatin antagonist for use in improving progression-free survival in a cancer patient, wherein said patient is treated with a chemotherapeutic agent. 
     
     
         33 . A myostatin antagonist for use according to  claim 32 , wherein said chemotherapeutic agent is include platinum-containing anti-cancer drugs such as cisplatin or carboplatin, or a mTOR inhibitor such as everolimus. 
     
     
         34 . A myostatin antagonist for use according to  claims 32 - 33  wherein said myostatin antagonist is an ActRII receptor inhibitor. 
     
     
         35 . A myostatin antagonist for use according to  claim 34  wherein said ActRII receptor inhibitor is an anti-ActRII receptor antibody. 
     
     
         36 . A myostatin antagonist for use according to  claim 35  wherein said anti-ActRII receptor antibody is bimagrumab. 
     
     
         37 . A method of treating a subject having cancer cachexia which comprises administering to said subject an ActRII receptor inhibitor in quantity which is effective against said cancer cachexia. 
     
     
         38 . The method of  claim 37 , wherein cancer cachexia is due to treatment with a chemotherapeutic agent. 
     
     
         39 . The method of  claim 38 , wherein the chemotherapeutic agent is a platinum-containing anti-cancer agent. 
     
     
         40 . The method of any  claims 37 - 39 , wherein treating cancer cachexia is reducing body weight loss. 
     
     
         41 . A method of delaying time to progression of cancer in a subject having cancer which comprises administering to said subject an ActRII receptor inhibitor in quantity which is effective in delaying time to progression of cancer. 
     
     
         42 . A method of delaying time to progression of cancer in a subject having cancer cachexia which comprising administering to said subject an ActRII receptor inhibitor in quantity which is effective in delaying time to progression of cancer cachexia. 
     
     
         43 . A method of prolonging cancer survival in a subject which comprising administering to said subject an ActRII receptor inhibitor in quantity which is effective in prolonging cancer survival. 
     
     
         44 . The method according to  claims 37 - 44 , wherein the ActRII receptor inhibitor is an anti-ActRII receptor antibody. 
     
     
         45 . The method according to  claim 44 , wherein the anti-ActRII receptor antibody is bimagrumab. 
     
     
         46 . A method of treating a subject having cancer cachexia which comprises administering to said subject a myostatin antagonist and an mTOR inhibitor. 
     
     
         47 . A method of treating a subject having an age-related condition which comprises administering to said subject a myostatin antagonist and an mTOR inhibitor. 
     
     
         48 . The method of  claims 46 - 47 , wherein the myostatin antagonist is an ActRII receptor inhibitor 
     
     
         49 . The method according to  claim 48 , wherein the ActRII receptor inhibitor is an anti-ActRII receptor antibody. 
     
     
         50 . The method according to  claim 49 , wherein the anti-ActRII receptor antibody is bimagrumab. 
     
     
         51 . The method of  claims 46 - 50 , wherein said mTOR inhibitor is everolimus. 
     
     
         52 . The method of  claims 46 - 50 , wherein the age related condition is selected from the group consisting of sarcopenia, skin atrophy, muscle wasting, brain atrophy, atherosclerosis, arteriosclerosis, pulmonary emphysema, osteoporosis, osteoarthritis, high blood pressure, erectile dysfunction, dementia, Huntington's disease, Alzheimer's disease, cataracts, age-related macular degeneration, prostate cancer, stroke, diminished life expectancy, impaired kidney function, and age-related hearing loss, aging-related mobility disability (e.g., frailty), cognitive decline, age related dementia, memory impairment, tendon stiffness, heart dysfunction such as cardiac hypertrophy and systolic and diastolic dysfunction, immunosenescence, cancer, obesity, and diabetes. 
     
     
         53 . A method of treatment according to any preceding use or combination.