Methods of treating autoimmunity using specific anti-IL-6 antibodies
Methods of treating individuals with autoimmune conditions characterized by elevated IL-6 levels comprising the administration of anti-IL-6 antibodies or antibody fragments are provided.
1. A method of inhibiting or treating an autoimmune disease characterized by elevated levels of interleukin-6 (IL-6) in a subject in need thereof comprising administering to said subject an effective amount of an anti-human IL-6 antibody or antigen-binding fragment comprising a variable light polypeptide comprising the complementarity regions (CDR's) of SEQ ID NO:4, 5 and 6 and a variable heavy polypeptide comprising the complementarity regions (CDR's) of SEQ ID NO:7, 8 or 120 and 9, wherein said administered amount of anti-IL-6 antibody or antigen-binding fragment effectively treats said autoimmune disease characterized by elevated levels of IL-6 which method further comprises (i) monitoring IL-6 and hemoglobin levels after antibody treatment, and/or (ii) administering another drug or therapy for treating anemia.
2. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment is a human, humanized or chimeric anti-human IL-6 antibody or fragment thereof.
3. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment contains a human Fc region.
4. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment is of the IgG1, IgG2, IgG3 or IgG4 isotype.
5. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment is of the IgG1 isotype.
6. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment is aglyclosylated.
7. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment contains an Fc region that has been modified to alter effector function, half-life, proteolysis, and/or glycosylation.
8. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment binds to IL-6 with a dissociation constant (K D ) of less than or equal to 5×10 −7 M −1 , 10 −7 M −1 , 5×10 −8 M −1 , 10 −8 M −1 , 5×10 −9 M −1 , 10 −9 M− 1 , 5×10 −10 M −1 , 10 −10 M −1 , 5×10 −11 M −1 , 10 −11 M −1 , 5×10 −12 M −1 , 10 −12 M −1 , 5×10 −13 M −1 , or 10 −13 M −1 .
9. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment binds to IL-6 with a dissociation constant (K D ) of less than or equal to 5×10 −11 M −1 .
10. The method of claim 1 wherein said administered anti-human IL-6 antibody or fragment binds to IL-6 with a dissociation constant (K D ) of less than or equal to 5×10 −12 M −1 .
11. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment is a humanized antibody or antibody fragment.
12. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment is a Fab, F(ab')2, Fv or scFv, camelbody, nanobody, or an IgNAR.
13. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment binds to IL-6 with a dissociation constant of less than or equal to 5×10 −10 M −1 .
14. The method of claim 1 , wherein said administered anti-human IL-6 antibody or fragment binds to IL-6 with an off-rate (K off ) of less than or equal to 10 −4 S −1 , 5×10 −5 S −1 , 10 −5 S −1 , 5×10 −6 S −1 , 10 −6 S −1 , 5×10 −7 S −1 , or 10 −7 S −1 .
15. The method of claim 1 , wherein the anti-IL-6 antibody or antibody fragment comprising said CDRs contains a variable heavy chain polypeptide identical to the polypeptide in SEQ ID NO:657 and a variable light chain identical to the polypeptide in SEQ ID NO:20.
16. The method of claim 1 , wherein said antibody or antibody fragment further comprises the heavy constant and light constant sequences in SEQ ID NO:588 and SEQ ID NO:586.
17. The method of claim 1 wherein the anti-IL-6 antibody comprising said CDRs contains a light chain polypeptide identical to the polypeptide in SEQ ID NO:586 and a heavy chain identical to the polypeptide in SEQ ID NO:588.