Anti-NGF antibodies for the treatment of various disorders

Abstract

The present invention relates generally to methods of using anti-NGF antibodies in the treatment of various NGF-related disorders, including asthma, arthritis and psoriasis. The methods are effective in treating these disorder in a patient without having a significant adverse effect on the immune system of the patient.

1 . A method of controlling a Nerve Growth Factor-related (NGF-related) disorder in a human patient, comprising administering to said patient an effective amount of an anti-human NGF (anti-hNGF) monoclonal antibody capable of binding hNGF with an affinity in the nanomolar or subnanomolar range, and inhibiting the binding of hNGF to human TrkA (hTrkA) in vivo, wherein said antibody has no significant adverse effect on the immune system of said patient. 
     
     
         2 . The method of  claim 1  wherein the binding affinity of said antibody to hNGF is about 0.10 to about 0.80 nM. 
     
     
         3 . The method of  claim 1  wherein said anti-hNGF monoclonal antibody recognizes an hNGF epitope selected from the group consisting of
 a) an epitope comprising the overlapping NGF-TrkA and p75 binding region β-turn A′-A″ (V-1) and the dominant TrkA binding region in β-sheet C; 
 b) an epitope comprising i) residues K32, K34 and E35 of hNGF; ii) residues Y79 and T81 of hNGF; iii) residues H84 and K88 of hNGF; iv) residue R103 of hNGF; v) residue E11 of hNGF; vi) residue Y52 of hNGF; and vii) residues L112 and S113 of hNGF; and 
 c) a sterically overlapping epitope of a) or b). 
 
     
     
         4 . The method of  claim 1  wherein the NGF-related disorder is selected from pain, thermal hyperalgesia, and airway hyperreactivity. 
     
     
         5 . The method of  claim 4  wherein said pain is chronic pain. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1  wherein said antibody is also able to bind murine NGF (muNGF). 
     
     
         8 . The method of  claim 1  wherein said antibody is an antibody fragment. 
     
     
         9 . The method of  claim 8  wherein said antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2 , Fv fragments, diabodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1  wherein said antibody is a chimeric, humanized, human, or bispecific antibody. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The method of  claim 11  wherein said bispecific antibody has an anti-IgE specificity.) 
     
     
         16 . The method of  claim 1  wherein said NGF-related disorder is other than a disorder associated with the effect of NGF on the neuronal system. 
     
     
         17 . The method of  claim 16  wherein said NGF-related disorder is an inflammatory condition. 
     
     
         18 . The method of  claim 17  wherein said inflammatory condition is selected from the group consisting of asthma, multiple sclerosis, arthritis, lupus erythematosus, and psoriasis. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 18  wherein said arthritis is rheumatoid arthritis. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 17  wherein said antibody is administered in combination with another therapeutic agent for the treatment of said inflammatory condition. 
     
     
         24 . The method of  claim 18  wherein said antibody is administered in combination with a corticosteroid, an anti-IgE antibody, or a therapeutic agent for the treatment of rheumatoid arthritis. 
     
     
         25 . The method of  claim 24  wherein said corticosteroid is bectomethasone diproprionate (BDP). 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 24  wherein said anti-IgE antibody is rhuMAb-E25 or rhuMAb-E26. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 24  wherein said other therapeutic agent for the treatment of rheumatoid arthritis is an anti-Tumor Necrosis Factor (anti-TNF) antibody or an antibody or immunoadhesin specifically binding a TNF receptor. 
     
     
         30 . A pharmaceutical composition comprising a chimeric, humanized or human anti-human NGF (anti-hNGF) monoclonal antibody capable of binding hNGF with an affinity in the nanomolar or subnanomolar range, and inhibiting the binding of hNGF to human TrkA (hTrkA) in vivo, wherein said antibody has no significant adverse effect on the immune system of a patient, in combination with a pharmaceutically acceptable carrier. 
     
     
         31 . The pharmaceutical composition of  claim 30  wherein said antibody is an antibody fragment. 
     
     
         32 . The pharmaceutical composition of  claim 31  wherein said-antibody fragment is selected from the group consisting of Fab, Fab′, F(ab′) 2 , Fv fragments, diabodies, single-chain antibody molecules, and multispecific antibodies formed from antibody fragments. 
     
     
         33 . The pharmaceutical composition of  claim 30  wherein said antibody is a chimeric, humanized, human, or bispecific antibody. 
     
     
         34 . The pharmaceutical composition of  claim 33  wherein said bispecific antibody is capable of specific binding to native human IgE, native human tumor necrosis factor (TNF), or a native human TNF receptor. 
     
     
         35 . The pharmaceutical composition of  claim 30  wherein said anti-hNGF monoclonal antibody recognizes an hNGF epitope selected from the group consisting of
 a) an epitope comprising the overlapping NGF-TrkA and p75 binding region β-turn A′-A″ (V-1) and the dominant TrkA binding region in β-sheet C; 
 b) an epitope comprising i) residues K32, K34 and E35 of hNGF; ii) residues Y79 and T81 of hNGF; iii) residues H84 and K88 of hNGF; iv) residue R103 of hNGF; v) residue E11 of hNGF; vi) residue Y52 of hNGF; and vii) residues L112 and S113 of hNGF; and 
 c) a sterically overlapping epitope of a) or b). 
 
     
     
         36 . The pharmaceutical composition of  claim 30  further comprising another pharmaceutically active ingredient. 
     
     
         37 . The pharmaceutical composition of  claim 36  wherein said other pharmaceutically active ingredient is suitable for the treatment of an inflammatory condition. 
     
     
         38 . The pharmaceutical composition of  claim 37  wherein said inflammatory condition is selected from the group consisting of asthma, multiple sclerosis, arthritis, lupus erythematosus and psoriasis. 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . The pharmaceutical composition of  claim 38  wherein said arthritis is rheumatoid arthritis. 
     
     
         42 . (canceled) 
     
     
         43 . An article of manufacture comprising: a container; a pharmaceutical composition of  claim 30 ; and instructions for using the composition of matter to control an NGF-related disorder in a human patient. 
     
     
         44 . The article of manufacture of  claim 43  further comprising a second pharmaceutically active ingredient. 
     
     
         45 . The article of manufacture of  claim 44  wherein said second pharmaceutically active ingredient is suitable for the treatment of an inflammatory condition. 
     
     
         46 . The article of manufacture of  claim 45  wherein said inflammatory condition is selected from the group consisting of asthma, multiple sclerosis, arthritis, lupus erythematosus and psoriasis. 
     
     
         47 . The article of manufacture of  claim 43  further comprising a second container with a composition contained therein, wherein the composition comprises a second antibody which binds an NGF receptor and blocks ligand activation of said NGF receptor when bound.