ANTAGONISTS OF IL-6 TO PREVENT OR TREAT CACHEXIA, WEAKNESS, FATIGUE, AND/OR FEVER
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.