ANTI-IL-6 ANTIBODIES FOR THE TREATMENT OF ORAL MUCOSITIS
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.