Anti-il-6 antibodies for the treatment of oral mucositis

Abstract

The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat mucositis (e.g., oral mucositis) including persons on a treatment regimen with a drug or chemotherapy and/or radiation for cancer (e.g., head and neck cancer) that is associated with increased risk of mucositis, including oral mucositis.

1 - 481 . (canceled) 
     
     
         482 . Compositions for use in therapy comprising
 (i) a first composition comprising hematopoietic stem cells for transplant (“HSCT”) in a subject in need thereof; and   (ii) a second composition comprising an effective amount of an anti-interleukin 6 (IL-6) antibody or antibody fragment thereof that binds IL-6, wherein said antibody or fragment thereof comprises the variable light (VL) complementarity determining regions (CDRs) in SEQ ID NO:4, 5 and 6, and the variable heavy (VH) CDRs in SEQ ID NO:7, 8 or 120, and 9, respectively;   
       wherein the combined use of said compositions in a subject in need thereof reduces mucositis and/or diarrhea as compared to when said composition comprising hematopoietic stem cells is administered alone. 
     
     
         483 . Compositions for use in therapy comprising
 (i) a first composition comprising bone marrow cells for transplant in a subject in need thereof; and   (ii) a second composition comprising an effective amount of an anti-interleukin 6 (IL-6) antibody or antibody fragment thereof that binds IL-6, wherein said antibody or fragment thereof comprises the variable light (VL) complementarity determining regions (CDRs) in SEQ ID NO:4, 5 and 6, and the variable heavy (VH) CDRs in SEQ ID NO:7, 8 or 120, and 9, respectively;   
       wherein the combined use of said compositions in a subject in need thereof reduces mucositis and/or diarrhea as compared to when said composition comprising bone marrow is administered alone. 
     
     
         484 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition is suitable for subcutaneous administration. 
     
     
         485 . The compositions of  claim 483 , wherein said anti-IL-6 antibody containing composition is suitable for subcutaneous administration. 
     
     
         486 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition is suitable for intravenous administration. 
     
     
         487 . The compositions of  claim 483 , wherein said anti-IL-6 antibody containing composition is suitable for intravenous administration. 
     
     
         488 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition comprises between about 0.1 and 20 mg/kg of body weight of recipient subject of said IL-6 antibody. 
     
     
         489 . The compositions of  claim 483 , wherein said anti-IL-6 antibody containing composition comprises between about 0.1 and 20 mg/kg of body weight of recipient subject of said IL-6 antibody. 
     
     
         490 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition comprises at least 25, 80, 100, 160, 200, or 320 mg of the anti-IL-6 antibody. 
     
     
         491 . The compositions of  claim 483 , wherein said anti-IL-6 antibody containing composition comprises at least 25, 80, 100, 160, 200, or 320 mg of the anti-IL-6 antibody. 
     
     
         492 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition comprises a concentration of said anti-IL-6 antibody or antibody fragment which is at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg/mL or at least about 10-100 mg/mL. 
     
     
         493 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition comprises a concentration of said anti-IL-6 antibody or antibody fragment which is at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg/mL or at least about 10-100 mg/mL. 
     
     
         494 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition comprises Histidine base, Histidine HCl sorbitol, and Polysorbate 80. 
     
     
         495 . The compositions of  claim 483 , wherein said anti-IL-6 antibody containing composition comprises Histidine base, Histidine HCl sorbitol, and Polysorbate 80. 
     
     
         496 . The compositions of  claim 482 , wherein said anti-IL-6 antibody containing composition comprises about 5 mM Histidine base, about 5 mM Histidine HCl to make final pH 6, 250 mM sorbitol, and 0.015% (w/w) Polysorbate 80. 
     
     
         497 . The compositions of  claim 483 , wherein said anti-IL-6 antibody containing composition comprises about 5 mM Histidine base, about 5 mM Histidine HCl to make final pH 6, 250 mM sorbitol, and 0.015% (w/w) Polysorbate 80. 
     
     
         498 . The compositions of  claim 482 , wherein said anti-IL-6 antibody or fragment thereof comprises at least one light chain comprising an amino acid sequence with at least about 90% sequence identity to an amino acid sequence of SEQ ID NO: 2, 20, 647, 651, 660, 666, 679, 687, 693, 699, 702, 706, or 709. 
     
     
         499 . The compositions of  claim 483 , wherein said anti-IL-6 antibody or fragment thereof comprises at least one light chain comprising an amino acid sequence with at least about 90% sequence identity to an amino acid sequence of SEQ ID NO: 2, 20, 647, 651, 660, 666, 679, 687, 693, 699, 702, 706, or 709. 
     
     
         500 . The compositions of  claim 482 , wherein said anti-IL-6 antibody or antibody fragment thereof comprises at least one heavy chain comprising an amino acid sequence with at least about 90% sequence identity to an amino acid sequence of SEQ ID NO: 3, 18, 19, 652, 654, 657, 658, 665, 668, 672, 676, 684, 688, 691, 692, 704, or 708. 
     
     
         501 . The compositions of  claim 483 , wherein said anti-IL-6 antibody or antibody fragment thereof comprises at least one heavy chain comprising an amino acid sequence with at least about 90% sequence identity to an amino acid sequence of SEQ ID NO: 3, 18, 19, 652, 654, 657, 658, 665, 668, 672, 676, 684, 688, 691, 692, 704, or 708. 
     
     
         502 . The compositions of  claim 482 , wherein said anti-IL-6 antibody or antibody fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 2, 20, 647, 651, 660, 666, 699, 702, 706, or 709. 
     
     
         503 . The compositions of  claim 483 , wherein said anti-IL-6 antibody or antibody fragment thereof comprises a light chain comprising the amino acid sequence of SEQ ID NO: 2, 20, 647, 651, 660, 666, 699, 702, 706, or 709. 
     
     
         504 . The compositions of  claim 482 , wherein said antibody or fragment thereof comprises a humanized light chain comprising the amino acid sequence of SEQ ID NO: 702. 
     
     
         505 . The compositions of  claim 483 , wherein said antibody or fragment thereof comprises a humanized light chain comprising the amino acid sequence of SEQ ID NO: 702. 
     
     
         506 . The compositions of  claim 482 , wherein said antibody or fragment thereof comprises a humanized light chain comprising the amino acid sequence of SEQ ID NO: 702 and a humanized heavy chain comprising the amino acid sequence of SEQ ID NO: 704. 
     
     
         507 . The compositions of  claim 483 , wherein said antibody or fragment thereof comprises a humanized light chain comprising the amino acid sequence of SEQ ID NO: 702 and a humanized heavy chain comprising the amino acid sequence of SEQ ID NO: 704. 
     
     
         508 . The compositions of  claim 483 , wherein said antibody or fragment thereof comprises a humanized light chain comprising the amino acid sequence of SEQ ID NO: 702. 
     
     
         509 . The compositions of  claim 482 , wherein said antibody or fragment thereof comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3, 18, 19, 652, 654, 657, 658, 665, 704, or 708. 
     
     
         510 . The compositions of  claim 482 , wherein said antibody or fragment thereof comprises a humanized heavy chain comprising the amino acid sequence of SEQ ID NO: 704. 
     
     
         511 . The compositions of  claim 483 , wherein said antibody or fragment thereof comprises a humanized heavy chain comprising the amino acid sequence of SEQ ID NO: 704.