Claims for Patent: 9,765,138

Summary for Patent: 9,765,138

Title:	Isolated anti-IL-6 antibodies
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 rheumatoid arthritis.
Inventor(s):	Smith; Jeffrey T. L. (Bellevue, WA)
Assignee:	ALDERBIO HOLDINGS LLC (Las Vegas, NV)
Application Number:	14/674,720
Patent Claims:	1. An antibody formulation comprising a therapeutically effective dosage of an anti-IL-6 antibody or antibody fragment wherein the variable light (VL) CDR1, CDR2 and CDR3 polypeptides thereof respectively comprise the amino acid sequence of SEQ ID NO:4, 5 and 6 and the variable heavy (VH) CDR1, CDR2 and CDR3 polypeptides thereof which respectively comprise the amino acid sequence of SEQ ID NO:7, 8 or 120, and 9, and wherein the composition further 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. 2. An antibody formulation comprising a therapeutically effective dosage of an anti-IL-6 antibody or antibody fragment wherein the variable light (VL) CDR1, CDR2 and CDR3 polypeptides thereof respectively comprise the amino acid sequence of SEQ ID NO:4, 5 and 6 and the variable heavy (VH) CDR1, CDR2 and CDR3 polypeptides thereof respectively comprise the amino acid sequence of s of SEQ ID NO:7, 8 or 120, and 9, and further wherein the composition comprises about 5 mM Histidine base, about 5 mM Histidine HCl to make final pH 6, 250 to 280 mM sorbitol or sorbitol in combination with sucrose, and 0.015% (w/w) Polysorbate 80, said formulation having a nitrogen headspace in the shipping vials. 3. The antibody formulation of claim 1, wherein the concentration of said anti-IL-6 antibody or antibody fragment is at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg/mL or at least about 10-100 mg/mL. 4. The antibody formulation of claim 2, wherein the concentration of said anti-IL-6 antibody or antibody fragment is at least about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg/mL or at least about 10-100 mg/mL. 5. The antibody formulation of claim 1, wherein said composition is formulated for subcutaneous or intravenous administration. 6. The antibody formulation of claim 2, wherein said composition is formulated for subcutaneous or intravenous administration. 7. The antibody formulation of claim 1, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 709. 8. The antibody formulation of claim 2, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 709. 9. The antibody formulation of claim 1, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 709. 10. The antibody formulation of claim 2, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 709. 11. The antibody formulation of claim 1, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence identical to SEQ ID NO: 709. 12. The antibody formulation of claim 2, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable light chain polypeptide comprising an amino acid sequence identical to SEQ ID NO: 709. 13. The antibody formulation of claim 1, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 657. 14. The antibody formulation of claim 2, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 657. 15. The antibody formulation of claim 1, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 657. 16. The antibody formulation of claim 2, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence having at least 95% identity to SEQ ID NO: 657. 17. The antibody formulation of claim 1, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence identical to SEQ ID NO: 657. 18. The antibody formulation of claim 2, wherein said antibody or antibody fragment containing said CDR polypeptides comprises a variable heavy chain polypeptide comprising an amino acid sequence identical to SEQ ID NO: 657. 19. The antibody formulation of claim 1, wherein said anti-IL-6 antibody comprises the constant light chain amino acid sequence contained in SEQ ID NO: 586 and the constant heavy chain amino acid sequence contained in SEQ ID NO: 588. 20. The antibody formulation of claim 2, wherein said anti-IL-6 antibody comprises the constant light chain amino acid sequence contained in SEQ ID NO: 586 and the constant heavy chain amino acid sequence contained in SEQ ID NO: 588. 21. The antibody formulation of claim 1, wherein said composition further comprises methotrexate. 22. The antibody formulation of claim 2, wherein said composition further comprises methotrexate. 23. The antibody formulation of claim 1 wherein said composition further comprises at least one anti-inflammatory agent, analgesic agent, or disease-modifying antirheumatic drug (DMARD). 24. The antibody formulation of claim 2 wherein said composition further comprises at least one anti-inflammatory agent, analgesic agent, or disease-modifying antirheumatic drug (DMARD). 25. The antibody formulation of claim 1, wherein said anti-inflammatory agent is selected from the group consisting of steroids, Cortisone, Glucocorticoids, prednisone, prednisolone, Hydrocortisone (Cortisol), Cortisone acetate, Methylprednisolone, Dexamethasone, Betamethasone, Triamcinolone, Beclomethasone, and Fludrocortisone acetate, non-steroidal anti-inflammatory drug (NSAIDs), ibuprofen, naproxen, meloxicam, etodolac, nabumetone, sulindac, tolementin, choline magnesium salicylate, diclofenac, diflunisal, indomethacin, Ketoprofen, Oxaprozin, piroxicam, and nimesulide, Salicylates, Aspirin (acetylsalicylic acid), Diflunisal, Salsalate, p-amino phenol derivatives, Paracetamol, phenacetin, Propionic acid derivatives, Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin, Loxoprofen, Acetic acid derivatives, Indomethacin, Sulindac, Etodolac, Ketorolac, Diclofenac, Nabumetone, Enolic acid (Oxicam) derivatives, Piroxicam, Meloxicam, Tenoxicam, Droxicam, Lornoxicam, Isoxicam, Fenamic acid derivatives (Fenamates), Mefenamic acid, Meclofenamic acid, Flufenamic acid, Tolfenamic acid, Selective COX-2 inhibitors (Coxibs), Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, Sulphonanilides, Nimesulide, and Licofelone, the analgesic agent is selected from the group consisting of NSAIDs, COX-2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, acetaminophen, opiates, Dextropropoxyphene, Codeine, Tramadol, Anileridine, Pethidine, Hydrocodone, Morphine, Oxycodone, Methadone, Diacetylmorphine, Hydromorphone, Oxymorphone, Levorphanol, Buprenorphine, Fentanyl, Sufentanyl, Etorphine, Carfentanil, dihydromorphine, dihydrocodeine, Thebaine, Papaverine, diproqualone, Flupirtine, Tricyclic antidepressants, and lidocaine, the said DMARD is selected from the group consisting of mycophenolate mofetil (CellCept), calcineurin inhibitors, cyclosporine, sirolimus, everolimus, oral retinoids, azathioprine, fumeric acid esters, D-penicillamine, cyclophosphamide, immunoadsorption column, Prosorba.RTM. column, a gold salt, auranofin, sodium aurothiomalate (Myocrisin), hydroxychloroquine, chloroquine, leflunomide, methotrexate (MTX), minocycline, sulfasalazine (SSZ), tumor necrosis factor alpha (TNFa) blockers, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi)), anakinra (Kineret), monoclonal antibodies against B cells, rituximab (Rituxan)), T cell costimulation blockers, abatacept (Orencia), Interleukin 6 (IL-6) blockers, tocilizumab, RoActemra, and Actemra. 26. The antibody formulation of claim 2, wherein said anti-inflammatory agent is selected from the group consisting of steroids, Cortisone, Glucocorticoids, prednisone, prednisolone, Hydrocortisone (Cortisol), Cortisone acetate, Methylprednisolone, Dexamethasone, Betamethasone, Triamcinolone, Beclomethasone, and Fludrocortisone acetate, non-steroidal anti-inflammatory drug (NSAIDs), ibuprofen, naproxen, meloxicam, etodolac, nabumetone, sulindac, tolementin, choline magnesium salicylate, diclofenac, diflunisal, indomethacin, Ketoprofen, Oxaprozin, piroxicam, and nimesulide, Salicylates, Aspirin (acetylsalicylic acid), Diflunisal, Salsalate, p-amino phenol derivatives, Paracetamol, phenacetin, Propionic acid derivatives, Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin, Loxoprofen, Acetic acid derivatives, Indomethacin, Sulindac, Etodolac, Ketorolac, Diclofenac, Nabumetone, Enolic acid (Oxicam) derivatives, Piroxicam, Meloxicam, Tenoxicam, Droxicam, Lornoxicam, Isoxicam, Fenamic acid derivatives (Fenamates), Mefenamic acid, Meclofenamic acid, Flufenamic acid, Tolfenamic acid, Selective COX-2 inhibitors (Coxibs), Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, Sulphonanilides, Nimesulide, and Licofelone, the analgesic agent is selected from the group consisting of NSAIDs, COX-2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, Parecoxib, Lumiracoxib, Etoricoxib, Firocoxib, acetaminophen, opiates, Dextropropoxyphene, Codeine, Tramadol, Anileridine, Pethidine, Hydrocodone, Morphine, Oxycodone, Methadone, Diacetylmorphine, Hydromorphone, Oxymorphone, Levorphanol, Buprenorphine, Fentanyl, Sufentanyl, Etorphine, Carfentanil, dihydromorphine, dihydrocodeine, Thebaine, Papaverine, diproqualone, Flupirtine, Tricyclic antidepressants, and lidocaine, the said DMARD is selected from the group consisting of mycophenolate mofetil (CellCept), calcineurin inhibitors, cyclosporine, sirolimus, everolimus, oral retinoids, azathioprine, fumeric acid esters, D-penicillamine, cyclophosphamide, immunoadsorption column, Prosorba.RTM. column, a gold salt, auranofin, sodium aurothiomalate (Myocrisin), hydroxychloroquine, chloroquine, leflunomide, methotrexate (MTX), minocycline, sulfasalazine (SSZ), tumor necrosis factor alpha (TNFa) blockers, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi)), anakinra (Kineret), monoclonal antibodies against B cells, rituximab (Rituxan)), T cell costimulation blockers, abatacept (Orencia), Interleukin 6 (IL-6) blockers, tocilizumab, RoActemra, and Actemra. 27. The antibody formulation of claim 1, wherein the anti-IL-6 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:704 and a light chain comprising the amino acid sequence of SEQ ID NO:702. 28. The antibody formulation of claim 2, wherein the anti-IL-6 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:704 and a light chain comprising the amino acid sequence of SEQ ID NO:702.

Details for Patent 9,765,138

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2028-11-25
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2028-11-25
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2028-11-25
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2028-11-25
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2028-11-25
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2028-11-25