Claims for Patent: 9,447,184

Summary for Patent: 9,447,184

Title:	IL-1 binding proteins
Abstract:	Proteins that bind IL-1.alpha. and IL-1.beta. are described along with their use in compositions and methods for treating, preventing, and diagnosing IL-1-related disorders and for detecting IL-1.alpha. and IL-1.beta. in cells, tissues, samples, and compositions.
Inventor(s):	Wu; Chengbin (Shanghai, CN), Ambrosi; Dominic J. (Shrewsbury, MA), Hsieh; Chung-ming (Newton, MA), Ghayur; Tariq (Holliston, MA)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	14/141,317
Patent Claims:	1. A method for treating a subject for a disorder in which IL-1 activity is detrimental comprising administering to the subject a binding protein, wherein the binding protein comprises first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first heavy chain variable domain; VD2 is a second heavy chain variable domain; C is a heavy chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 is an Fc region; and n is independently 0 or 1; and wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first light chain variable domain; VD2 is a second light chain variable domain; C is a light chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 does not comprise an Fc region; and n is independently 0 or 1; wherein, in said first polypeptide chain, VD1 comprises an amino acid sequence of SEQ ID NO: 204; and VD2 comprises an amino acid of SEQ ID NO: 213; wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence of SEQ ID NO: 238; and VD2 comprises an amino acid sequence of SEQ ID NO: 216; and wherein the binding protein binds human IL-1.beta. and human IL-1.alpha., such that treatment for the disorder is achieved. 2. The method according to claim 1, wherein said administering to the subject is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intra-articular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal. 3. A method of treating a patient suffering from a disorder in which IL-1 is detrimental comprising the step of administering a binding protein before, concurrently with, or after the administration of a second agent, wherein the binding protein comprises first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first heavy chain variable domain; VD2 is a second heavy chain variable domain; C is a heavy chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 is an Fc region; and n is independently 0 or 1; and wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first light chain variable domain; VD2 is a second light chain variable domain; C is a light chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 does not comprise an Fc region; and n is independently 0 or 1; wherein, in said first polypeptide chain, VD1 comprises an amino acid sequence of SEQ ID NO: 204; and VD2 comprises an amino acid sequence of SEQ ID NO: 213; wherein, in said second polypeptide chain, VD1 comprises an amino acid sequence of SEQ ID NO: 238; and VD2 comprises an amino acid sequence of SEQ ID NO: 216; and wherein the binding protein binds human IL-1.beta. and human IL-1.alpha.; wherein the second agent is selected from the group consisting of: an antibody, or fragment thereof, capable of binding human IL-1.beta.; an antibody, or fragment thereof, capable of binding human IL-1.alpha.; methotrexate; a corticosteroid; a beta-agonist; an antagonist of a leukotriene; an antagonist of a leukotriene receptor; ADVAIR; an IgE inhibitor; an anti-IgE antibody; XOLAIR; a phosphodiesterase inhibitor; a PDE4 inhibitor; a xanthine; an anticholinergic drug; a mast cell-stabilizing agent; Cromolyn; an IL-4 inhibitor; an IL-5 inhibitor; an eotaxin/CCR3 inhibitor; an antagonist of histamine; an antagonist of a histamine receptor, an antagonist of prostaglandin D; an inhibitor of receptor DP1; an inhibitor of CRTH2; a TNF antagonist; a soluble fragment of a TNF receptor; ENBREL; a TNF enzyme antagonist; a TNF converting enzyme (TACE) inhibitor; a muscarinic receptor antagonist; a TGF-beta antagonist; interferon gamma; perfenidone; a chemotherapeutic agent, leflunomide; sirolimus (rapamycin) or an analog thereof, CCI-779; a COX2 or cPLA2 inhibitor; a non-steroidal anti-inflammatory drug (NSAID); an immunomodulator; a p38 inhibitor; a TPL-2 inhibitor; an MK-2 inhibitor; an NF.kappa.B inhibitor; budenoside; epidermal growth factor; cyclosporine; sulfasalazine; an amino salicylate; 6-mercaptopurine; azathioprine; metronidazole; a lipoxygenase inhibitor; mesalamine; olsalazine; balsalazide; an antioxidant; a thromboxane inhibitor; an IL-1 receptor antagonist; a growth factor; an elastase inhibitor; a pyridinyl-imidazole compound; an antibody or agonists of TNF, LT, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, EMAP-II, GM-CSF, FGF, or PDGF; an antibody to CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, CD90; FK506; mycophenolate mofetil; ibuprofen; prednisolone; an adensosine agonist; an antithrombotic agent; a complement inhibitor; an adrenergic agent; a kinase inhibitor; an IL-1.beta. converting enzyme inhibitors; a T-cell signaling inhibitor; a metalloproteinase inhibitor; an angiotensin converting enzyme inhibitor; soluble cytokine receptor; soluble p55 TNF receptor; soluble p75 TNF receptor; soluble IL-1RI; soluble IL-1RII; soluble IL-6R; an anti-inflammatory cytokine; IL-4; IL-10; IL-11; and TGF-.beta.. 4. A method for treating a subject for a disorder in which IL-1 activity is detrimental comprising administering to the subject a binding protein, wherein the binding protein comprises first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first heavy chain variable domain; VD2 is a second heavy chain variable domain; C is a heavy chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 is an Fc region; and n is independently 0 or 1; and wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first light chain variable domain; VD2 is a second light chain variable domain; C is a light chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 does not comprise an Fc region; and n is independently 0 or 1; wherein said first polypeptide chain comprises an amino acid sequence of SEQ ID NO: 212; wherein said second polypeptide chain comprises an amino acid sequence of SEQ ID NO: 215; and wherein the binding protein binds human IL-1.beta. and human IL-1.alpha., such that treatment of the disorder is achieved. 5. The method according to claim 4, wherein said administering to the subject is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intra-articular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intramyocardial, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal, and transdermal. 6. A method of treating a patient suffering from a disorder in which IL-1 is detrimental comprising the step of administering a binding protein before, concurrently with, or after the administration of a second agent, wherein the binding protein comprises first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first heavy chain variable domain; VD2 is a second heavy chain variable domain; C is a heavy chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 is an Fc region; and n is independently 0 or 1; and wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n, wherein: VD1 is a first light chain variable domain; VD2 is a second light chain variable domain; C is a light chain constant domain; X1 is a linker with the proviso that it is not CH1; X2 does not comprise an Fc region; and n is independently 0 or 1; wherein said first polypeptide chain comprises an amino acid sequence of SEQ ID NO: 212; wherein said second polypeptide chain comprises an amino acid sequence of SEQ ID NO: 215; and wherein the binding protein binds human IL-1.beta. and human IL-1.alpha., wherein the second agent is selected from the group consisting of: an antibody, or fragment thereof, capable of binding human IL-1.beta.; an antibody, or fragment thereof, capable of binding human IL-1.alpha.; methotrexate; a corticosteroid; a beta-agonist; an antagonist of a leukotriene; an antagonist of a leukotriene receptor; ADVAIR; an IgE inhibitor; an anti-IgE antibody; XOLAIR; a phosphodiesterase inhibitor; a PDE4 inhibitor; a xanthine; an anticholinergic drug; a mast cell-stabilizing agent; Cromolyn; an IL-4 inhibitor; an IL-5 inhibitor; an eotaxin/CCR3 inhibitor; an antagonist of histamine; an antagonist of a histamine receptor, an antagonist of prostaglandin D; an inhibitor of receptor DP1; an inhibitor of CRTH2; a TNF antagonist; a soluble fragment of a TNF receptor; ENBREL; a TNF enzyme antagonist; a TNF converting enzyme (TACE) inhibitor; a muscarinic receptor antagonist; a TGF-beta antagonist; interferon gamma; perfenidone; a chemotherapeutic agent, leflunomide; sirolimus (rapamycin) or an analog thereof, CCI-779; a COX2 or cPLA2 inhibitor; a non-steroidal anti-inflammatory drug (NSAID); an immunomodulator; a p38 inhibitor; a TPL-2 inhibitor; an MK-2 inhibitor; an NF.kappa.B inhibitor; budenoside; epidermal growth factor; cyclosporine; sulfasalazine; an amino salicylate; 6-mercaptopurine; azathioprine; metronidazole; a lipoxygenase inhibitor; mesalamine; olsalazine; balsalazide; an antioxidant; a thromboxane inhibitor; an IL-1 receptor antagonist; a growth factor; an elastase inhibitor; a pyridinyl-imidazole compound; an antibody or agonists of TNF, LT, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, EMAP-II, GM-CSF, FGF, or PDGF; an antibody to CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, CD90; FK506; mycophenolate mofetil; ibuprofen; prednisolone; an adensosine agonist; an antithrombotic agent; a complement inhibitor; an adrenergic agent; a kinase inhibitor; an IL-1.beta. converting enzyme inhibitors; a T-cell signaling inhibitor; a metalloproteinase inhibitor; an angiotensin converting enzyme inhibitor; soluble cytokine receptor; soluble p55 TNF receptor; soluble p75 TNF receptor; soluble IL-1RI; soluble IL-1RII; soluble IL-6R; an anti-inflammatory cytokine; IL-4; IL-10; IL-11; and TGF-.beta.. 7. The method of claim 1, wherein the disorder is an inflammatory disorder. 8. The method of claim 3, wherein the disorder is an inflammatory disorder. 9. The method of claim 4, wherein the disorder is an inflammatory disorder. 10. The method of claim 6, wherein the disorder is an inflammatory disorder. 11. The method of claim 7, wherein said disorder is selected from the group consisting of: rheumatoid arthritis; osteoarthritis; juvenile chronic arthritis; septic arthritis; Lyme arthritis; psoriatic arthritis; and reactive arthritis. 12. The method of claim 8, wherein said disorder is selected from the group consisting of: rheumatoid arthritis; osteoarthritis; juvenile chronic arthritis; septic arthritis; Lyme arthritis; psoriatic arthritis; and reactive arthritis. 13. The method of claim 9, wherein said disorder is selected from the group consisting of: rheumatoid arthritis; osteoarthritis; juvenile chronic arthritis; septic arthritis; Lyme arthritis; psoriatic arthritis; and reactive arthritis. 14. The method of claim 10, wherein said disorder is selected from the group consisting of: rheumatoid arthritis; osteoarthritis; juvenile chronic arthritis; septic arthritis; Lyme arthritis; psoriatic arthritis; and reactive arthritis. 15. The method according to claim 1, wherein said first polypeptide chain comprises an amino acid sequence of SEQ ID NO: 212. 16. The method according to claim 1, wherein said second polypeptide chain comprises an amino acid sequence of SEQ ID NO: 215. 17. The method according to claim 3, wherein said first polypeptide chain comprises an amino acid sequence of SEQ ID NO: 212. 18. The method according to claim 3, wherein said second polypeptide chain comprises an amino acid sequence of SEQ ID NO: 215. 19. The method according to claim 1, wherein said first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212, and said second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 215. 20. The method according to claim 3, wherein said first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212, and said second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 215. 21. The method according to claim 11, wherein said first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212, and said second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 215. 22. The method according to claim 12, wherein said first polypeptide chain comprises the amino acid sequence of SEQ ID NO: 212, and said second polypeptide chain comprises the amino acid sequence of SEQ ID NO: 215. 23. The binding protein according to claim 21, wherein said heavy chain constant domain of the first polypeptide comprises SEQ ID NO: 214, and said light chain constant domain of the second polypeptide comprises SEQ ID NO: 5. 24. The binding protein according to claim 22, wherein said heavy chain constant domain of the first polypeptide comprises SEQ ID NO: 214, and said light chain constant domain of the second polypeptide comprises SEQ ID NO: 5. 25. The binding protein according to claim 13, wherein said heavy chain constant domain of the first polypeptide comprises SEQ ID NO: 214, and said light chain constant domain of the second polypeptide comprises SEQ ID NO: 5. 26. The binding protein according to claim 14, wherein said heavy chain constant domain of the first polypeptide comprises SEQ ID NO: 214, and said light chain constant domain of the second polypeptide comprises SEQ ID NO: 5.

Details for Patent 9,447,184

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2030-05-14
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2030-05-14
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2030-05-14