Antagonists of il-6 to prevent or treat cachexia, weakness, fatigue, and/or fever

Abstract

The present invention is directed to therapeutic methods and compositions, especially subcutaneous and intravenous composition using antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat cachexia, fever, weakness and/or fatigue in a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level. In another preferred embodiment, the patient's survivability or quality of life will preferably be improved.

1 - 101 . (canceled) 
     
     
         102 . A method for treating an allergic disorder or for alleviating an allergic response in a patient comprising a condition associated with elevated IL-6 (interleukin-6) comprising administering to the patient an anti-IL-6 antibody or an IL-6 binding antibody fragment comprising the variable light (V L ) chain CDR1 of SEQ ID NO:4, CDR2 of SEQ ID NO:5 and CDR3 of SEQ ID NO:6, and the variable heavy (V H ) chain CDR1 of SEQ ID NO:7, CDR2 of SEQ ID NO:8 or 120, and CDR3 of SEQ ID NO:9. 
     
     
         103 . The method of  claim 102 , wherein the anti-IL-6 antibody or an IL-6 binding antibody fragment comprises the variable light (V L ) chain CDR1 of SEQ ID NO:4, CDR2 of SEQ ID NO:5 and CDR3 of SEQ ID NO:6, and the variable heavy (V H ) chain CDR1 of SEQ ID NO:7, CDR2 of SEQ ID NO:120, and CDR3 of SEQ ID NO:9. 
     
     
         104 . A method for inhibiting an acute phase response in a patient comprising a condition associated with elevated IL-6 (interleukin-6) comprising administering to the patient an anti-IL-6 antibody or an IL-6 binding antibody fragment comprising the variable light (V L ) chain CDR1 of SEQ ID NO:4, CDR2 of SEQ ID NO:5 and CDR3 of SEQ ID NO:6, and the variable heavy (V H ) chain CDR1 of SEQ ID NO:7, CDR2 of SEQ ID NO:8 or 120, and CDR3 of SEQ ID NO:9. 
     
     
         105 . The method of  claim 104 , wherein the anti-IL-6 antibody or an IL-6 binding antibody fragment comprises the variable light (V L ) chain CDR1 of SEQ ID NO:4, CDR2 of SEQ ID NO:5 and CDR3 of SEQ ID NO:6, and the variable heavy (V H ) chain CDR1 of SEQ ID NO:7, CDR2 of SEQ ID NO:120, and CDR3 of SEQ ID NO:9. 
     
     
         106 . The method of  claim 102 , further comprising administration of an antagonist of a cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor. 
     
     
         107 . The method of  claim 104 , further comprising administration of an antagonist of a cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor. 
     
     
         108 . The method of  claim 106 , wherein the cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor is selected from tumor necrosis factor-α, Interferon γ, Interleukin 1α, Interleukin 1β, Interleukin 6, proteolysis inducing factor, leukemia-inhibitory factor, or any combination thereof or is selected from cannabis, dronabinol (Marinol®), nabilone (Cesamet), cannabidiol, cannabichromene, tetrahydrocannabinol, Sativex, megestrol acetate, or any combination thereof. 
     
     
         109 . The method of  claim 107 , wherein the cachexia-associated factor, weakness-associated factor, fatigue-associated factor, and/or fever-associated factor is selected from tumor necrosis factor-α, Interferon β, Interleukin 1α, Interleukin 1β, Interleukin 6, proteolysis inducing factor, leukemia-inhibitory factor, or any combination thereof or is selected from cannabis, dronabinol (Marinol®), nabilone (Cesamet), cannabidiol, cannabichromene, tetrahydrocannabinol, Sativex, megestrol acetate, or any combination thereof. 
     
     
         110 . The method of  claim 102 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment is aglycosylated and/or contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation. 
     
     
         111 . The method of  claim 104 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment is aglycosylated and/or contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation. 
     
     
         112 . The method of  claim 102 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment is human, humanized, single chain or chimeric. 
     
     
         113 . The method of  claim 104 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment is human, humanized, single chain or chimeric. 
     
     
         114 . The method of  claim 102 , wherein said anti anti-IL-6 antibody or IL-6 binding antibody fragment is administered to the patient with a frequency of about once every four weeks or eight weeks. 
     
     
         115 . The method of  claim 104 , wherein said anti anti-IL-6 antibody or IL-6 binding antibody fragment is administered to the patient with a frequency of about once every four weeks or eight weeks. 
     
     
         116 . The method of  claim 102 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment comprises a human Fc derived from IgG1, IgG2, IgG3, or IgG4. 
     
     
         117 . The method of  claim 104 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment comprises a human Fc derived from IgG1, IgG2, IgG3, or IgG4. 
     
     
         118 . The method of  claim 102 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment comprises a V H  chain having at least 98% identity with the V H  chain of SEQ ID NO:18 or 19, and a V L  chain having at least 98% identity with the V L  chain of SEQ ID NO:20. 
     
     
         119 . The method of  claim 104 , wherein said anti-IL-6 antibody or IL-6 binding antibody fragment comprises a V H  chain having at least 98% identity with the V H  chain of SEQ ID NO:18 or 19, and a V L  chain having at least 98% identity with the V L  chain of SEQ ID NO:20. 
     
     
         120 . The method of  claim 102 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises a V H  chain having at least 95% identity with the V H  chain of SEQ ID NO:18 or 19, and a V L  chain having at least 95% identity with the V L  chain of SEQ ID NO:20. 
     
     
         121 . The method of  claim 102 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises the V H  chain of SEQ ID NO:18 or 19, and the V L  chain of SEQ ID NO:20. 
     
     
         122 . The method of  claim 104 , wherein the anti-IL-6 antibody or IL-6 binding antibody fragment comprises the V H  chain of SEQ ID NO:18 or 19, and the V L  chain of SEQ ID NO:20. 
     
     
         123 . The method of  claim 102 , wherein the patient is administered the anti-IL-6 antibody or IL-6 binding antibody subcutaneously or intravenously. 
     
     
         124 . The method of  claim 104 , wherein the patient is administered the anti-IL-6 antibody or IL-6 binding antibody subcutaneously or intravenously.