Compositions and methods for increasing muscle growth

Abstract

This disclosure is in the field of anti-Activin receptor IIB (ActRIIB) antibodies. In particular, it relates to the use of said antibodies for treating muscle disorders, such as muscle wasting due to disease or disuse.

1 . An anti-ActRIIB antibody or functional fragment thereof that binds to ActRIIB between amino acids 19-134 of SEQ ID NO: 181. 
     
     
         2 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , wherein said antibody or functional fragment thereof is of the IgG 1  isotype. 
     
     
         3 . The anti-ActRIIB antibody or functional fragment thereof according to  claim 1 , which has altered effector function through mutation of the Fc region. 
     
     
         4 . An isolated polynucleotide sequence encoding an antibody or functional fragment thereof according to  claim 1 . 
     
     
         5 . A cloning or expression vector comprising one or more isolated polynucleotide sequences according to  claim 4 . 
     
     
         6 . An isolated host cell comprising one or more vectors according to  claim 5 . 
     
     
         7 . A process for the production of an anti-ActRIIB antibody or functional fragment thereof that binds to ActRIIB between amino acids 19-134 of SEQ ID NO: 181, comprising culturing the host cell of  claim 6  and isolating said antibody or functional fragment thereof. 
     
     
         8 . A pharmaceutical composition comprising an anti-ActRIIB antibody or functional fragment thereof of  claim 1 . 
     
     
         9 . A pharmaceutical composition according to  claim 8 , further comprising a pharmaceutically acceptable diluent or carrier. 
     
     
         10 . A pharmaceutical composition according to  claim 8 , further comprising one or more additional active agents. 
     
     
         11 . A pharmaceutical composition according to  claim 10 , wherein said one or more additional active agents is selected from IGF-1, IGF-2, a variant of IGF-1 or IGF-2, an anti-myostatin antibody, a myostatin propeptide, a myostatin decoy protein that binds ActRIIB but does not activate it, a beta 2 agonist, a Ghrelin agonist, a SARM, GH agonists/mimetics and follistatin. 
     
     
         12 . A method of treatment of a musculoskeletal disease or disorder in an individual in need thereof, comprising the step of administering an effective dose of an antibody or functional fragment thereof according to  claim 1 . 
     
     
         13 . The method according to  claim 12 , wherein the musculoskeletal disease or disorder is muscle atrophy, myopathy, myotonia, a congential myopathy, nemalene myopathy, multi/minicore myopathy and myotubular (centronuclear) myopathy, mitochondrial myopathy, familial periodic paralysis, inflammatory myopathy, metabolic myopathy, a glycogen or lipid storage disease, dermatomyositisis, polymyositis, inclusion body myositis, myositis ossificans, rhabdomyolysis and myoglobinurias; a dystrophy, Duchenne, Becker, myotonic, fascioscapulohumeral, Emery-Dreifuss, oculopharyngeal, scapulohumeral, limb girdle, Fukuyama, or a congenital muscular dystrophy, or hereditary distal myopathy; osteoporosis; a bone fracture; short stature; dwarfism; prolonged bed rest; voluntary inactivity; and/or involuntary inactivity. 
     
     
         14 . The method according to  claim 13 , wherein the individual has been pre-treated with IGF-1, IGF-2 or variants of IGF-1 or IGF-2, an anti-myostatin antibody, a myostatin propeptide, a myostatin decoy protein that binds ActRIIB but does not activate it, a beta 2 agonist, a Ghrelin agonist, a SARM, GH agonists/mimetics or follistatin. 
     
     
         15 . The method according to  claim 13 , wherein the individual has previously been refractive to treatment with IGF-1, IGF-2 or variants of IGF-1 or IGF-2, an anti-myostatin antibody, a myostatin propeptide, a myostatin decoy protein that binds ActRIIB but does not activate it, a beta 2 agonist, a Ghrelin agonist, a SARM, GH agonists/mimetics or follistatin. 
     
     
         16 . The method according to  claim 13 , wherein the individual is elderly, has spent time in a zero gravity environment, or has undergone a period of inactivity. 
     
     
         17 . The method according to  claim 13 , wherein the individual has a fracture to a limb or joint. 
     
     
         18 . The method according to  claim 13 , wherein the individual has undergone or is about to undergo, hip or knee replacement surgery.