Claims for Patent: 9,592,293

Summary for Patent: 9,592,293

Title:	Interleukin-13 binding proteins
Abstract:	The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.
Inventor(s):	Wu; Chengbin (Shanghai, CN), Dixon; Richard W. (Jefferson, MA), Belk; Jonathan P. (Sterling, MA), Argiriadi; Maria A. (Wayland, MA), Ying; Hua (Holden, MA), Cuff; Carolyn A. (Grafton, MA), Melim; Terry L. (Derry, NH), Kumar; Shankar (Pleasanton, CA), Hinton; Paul R. (Sunnyvale, CA), Chen; Yan (Fremont, CA)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	14/101,145
Patent Claims:	1. A method for reducing human IL-13 activity in a human subject suffering from a disorder in which IL-13 activity is detrimental, comprising administering to the human subject a binding protein, such that human IL-13 activity in the human subject is reduced, wherein said binding protein binds human IL-13 and comprises six CDRs, CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, and CDR-H3 comprise amino acid sequences independently selected from the group consisting of: TABLE-US-00027 CDR-H1 CDR-H2 CDR-H3 residues 31-35 of residues 50-66 of residues 99-105 of SEQ ID NO.: 32 SEQ ID NO.: 32 SEQ ID NO.: 32 residues 31-35 of residues 50-66 of residues 99-105 of SEQ ID NO.: 34 SEQ ID NO.: 34 SEQ ID NO.: 34 residues 31-35 of residues 50-66 of residues 99-109 of SEQ ID NO.: 36 SEQ ID NO.: 36 SEQ ID NO.: 36 residues 31-35 of residues 50-66 of residues 99-109 of SEQ ID NO.: 38 SEQ ID NO.: 38 SEQ ID NO.: 38 residues 31-35 of residues 50-66 of residues 99-112 of SEQ ID NO.: 39 SEQ ID NO.: 39 SEQ ID NO.: 39 residues 31-35 of residues 50-66 of residues 99-112 of SEQ ID NO.: 41 SEQ ID NO.: 41 SEQ ID NO.: 41 residues 31-35 of residues 50-66 of residues 99-100 of SEQ ID NO.: 42 SEQ ID NO.: 42 SEQ ID NO.: 42 residues 31-35 of residues 50-65 of residues 98-106 of SEQ ID NO.: 44 SEQ ID NO.: 44 SEQ ID NO.: 44 residues 31-37 of residues 52-67 of residues 100-112 of SEQ ID NO.: 46 SEQ ID NO.: 46 SEQ ID NO.: 46 residues 31-37 of residues 52-67 of residues 100-112 of SEQ ID NO.: 48 SEQ ID NO.: 48 SEQ ID NO.: 48 residues 31-37 of residues 52-67 of residues 100-112 of SEQ ID NO.: 50 SEQ ID NO.: 50 SEQ ID NO.: 50 residues 31-35 of residues 50-66 of residues 99-107 of SEQ ID NO.: 52 SEQ ID NO.: 52 SEQ ID NO.: 52 residues 31-35 of residues 50-65 of residues 98-107 of SEQ ID NO.: 54 SEQ ID NO.: 54 SEQ ID NO.: 54 residues 31-35 of residues 50-65 of residues 98-107 of SEQ ID NO.: 56 SEQ ID NO.: 56 SEQ ID NO.: 56 residues 31-35 of residues 50-65 of residues 98-107 of SEQ ID NO.: 58 SEQ ID NO.: 58 SEQ ID NO.: 58 residues 31-35 of residues 50-65 of residues 98-107 of SEQ ID NO.: 60 SEQ ID NO.: 60 SEQ ID NO.: 60 residues 31-35 of residues 50-65 of residues 98-107 of SEQ ID NO.: 62 SEQ ID NO.: 62 SEQ ID NO.: 62 and CDR-L1, CDR-L2, and CDR-L3 comprise amino acid sequences independently selected from the group consisting of: TABLE-US-00028 CDR-L1 CDR-L2 CDR-L3 residues 24-39 of residues 55-61 of residues 94-102 of SEQ ID NO.: 33 SEQ ID NO.: 33 SEQ ID NO.: 33 residues 24-39 of residues 55-61 of residues 94-102 of SEQ ID NO.: 35 SEQ ID NO.: 35 SEQ ID NO.: 35 residues 24-39 of residues 55-61 of residues 94-102 of SEQ ID NO.: 37 SEQ ID NO.: 37 SEQ ID NO.: 37 residues 24-39 of residues 55-61 of residues 94-102 of SEQ ID NO.: 40 SEQ ID NO.: 40 SEQ ID NO.: 40 residues 24-39 of residues 55-61 of residues 94-102 of SEQ ID NO.: 43 SEQ ID NO.: 43 SEQ ID NO.: 43 residues 24-40 of residues 56-62 of residues 95-103 of SEQ ID NO.: 45 SEQ ID NO.: 45 SEQ ID NO.: 45 residues 24-34 of residues 50-56 of residues 89-97 of SEQ ID NO.: 47 SEQ ID NO.: 47 SEQ ID NO.: 47 residues 24-34 of residues 50-56 of residues 89-97 of SEQ ID NO.: 49 SEQ ID NO.: 49 SEQ ID NO.: 49 residues 24-34 of residues 50-56 of residues 89-97 of SEQ ID NO.: 51 SEQ ID NO.: 51 SEQ ID NO.: 51 residues 23-36 of residues 52-58 of residues 91-99 of SEQ ID NO.: 53 SEQ ID NO.: 53 SEQ ID NO.: 53 residues 24-38 of residues 54-60 of residues 93-101 of SEQ ID NO.: 55 SEQ ID NO.: 55 SEQ ID NO.: 55 residues 24-38 of residues 54-60 of residues 93-101 of SEQ ID NO.: 57 SEQ ID NO.: 57 SEQ ID NO.: 57 residues 24-38 of residues 54-60 of residues 93-101 of SEQ ID NO.: 59 SEQ ID NO.: 59 SEQ ID NO.: 59 residues 24-38 of residues 54-60 of residues 93-101 of SEQ ID NO.: 61 SEQ ID NO.: 61 SEQ ID NO.: 61 residues 24-38 of residues 54-60 of residues 93-101 of SEQ ID NO.: 63 SEQ ID NO.: 63 SEQ ID NO.: 63 residues 24-34 of residues 50-56 of residues 89-97 of SEQ ID NO: 92 SEQ ID NO: 92 SEQ ID NO: 92 residues 24-34 of residues 50-56 of residues 89-97 of SEQ ID NO: 93 SEQ ID NO: 93 SEQ ID NO: 93 residues 24-34 of residues 50-56 of residues 89-97 of SEQ ID NO: 94 SEQ ID NO: 94 SEQ ID NO: 94 wherein said disorder is selected from the group consisting of respiratory disorders; asthma; allergic and nonallergic asthma; asthma due to infection; asthma due to infection with respiratory syncytial virus (RSV); chronic obstructive pulmonary disease (COPD); other conditions involving airway inflammation; eosinophilia; fibrosis and excess mucus production; cystic fibrosis; pulmonary fibrosis; atopic disorders; atopic dermatitis; urticaria; eczema; allergic rhinitis; and allergic enterogastritis; inflammatory and/or autoimmune conditions of the skin; inflammatory and/or autoimmune conditions of gastrointestinal organs; inflammatory bowel diseases (IBD); ulcerative colitis; Crohn's disease; inflammatory and/or autoimmune conditions of the liver; liver cirrhosis; liver fibrosis; liver fibrosis caused by hepatitis B and/or C virus; scleroderma; tumors or cancers; hepatocellular carcinoma; glioblastoma; lymphoma; Hodgkin's lymphoma; viral infections; HTLV-1 infection; suppression of expression of protective type 1 immune responses, and suppression of expression of protective type 1 immune responses during vaccination. 2. A method for treating a subject for a disorder in which IL-13 activity is detrimental comprising administering to the subject a binding protein such that treatment is achieved, wherein said binding binds human IL-13 and comprises six CDRs, CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, and CDR-H3 comprise amino acid sequences independently selected from the group consisting of: TABLE-US-00029 CDR-H1 CDR-H2 CDR-H3 residues 31-35 of SEQ ID NO.: 32 residues 50-66 of SEQ ID NO.: 32 residues 99-105 of SEQ ID NO.: 32 residues 31-35 of SEQ ID NO.: 34 residues 50-66 of SEQ ID NO.: 34 residues 99-105 of SEQ ID NO.: 34 residues 31-35 of SEQ ID NO.: 36 residues 50-66 of SEQ ID NO.: 36 residues 99-109 of SEQ ID NO.: 36 residues 31-35 of SEQ ID NO.: 38 residues 50-66 of SEQ ID NO.: 38 residues 99-109 of SEQ ID NO.: 38 residues 31-35 of SEQ ID NO.: 39 residues 50-66 of SEQ ID NO.: 39 residues 99-112 of SEQ ID NO.: 39 residues 31-35 of SEQ ID NO.: 41 residues 50-66 of SEQ ID NO.: 41 residues 99-112 of SEQ ID NO.: 41 residues 31-35 of SEQ ID NO.: 42 residues 50-66 of SEQ ID NO.: 42 residues 99-100 of SEQ ID NO.: 42 residues 31-35 of SEQ ID NO.: 44 residues 50-65 of SEQ ID NO.: 44 residues 98-106 of SEQ ID NO.: 44 residues 31-37 of SEQ ID NO.: 46 residues 52-67 of SEQ ID NO.: 46 residues 100-112 of SEQ ID NO.: 46 residues 31-37 of SEQ ID NO.: 48 residues 52-67 of SEQ ID NO.: 48 residues 100-112 of SEQ ID NO.: 48 residues 31-37 of SEQ ID NO.: 50 residues 52-67 of SEQ ID NO.: 50 residues 100-112 of SEQ ID NO.: 50 residues 31-35 of SEQ ID NO.: 52 residues 50-66 of SEQ ID NO.: 52 residues 99-107 of SEQ ID NO.: 52 residues 31-35 of SEQ ID NO.: 54 residues 50-65 of SEQ ID NO.: 54 residues 98-107 of SEQ ID NO.: 54 residues 31-35 of SEQ ID NO.: 56 residues 50-65 of SEQ ID NO.: 56 residues 98-107 of SEQ ID NO.: 56 residues 31-35 of SEQ ID NO.: 58 residues 50-65 of SEQ ID NO.: 58 residues 98-107 of SEQ ID NO.: 58 residues 31-35 of SEQ ID NO.: 60 residues 50-65 of SEQ ID NO.: 60 residues 98-107 of SEQ ID NO.: 60 residues 31-35 of SEQ ID NO.: 62 residues 50-65 of SEQ ID NO.: 62 residues 98-107 of SEQ ID NO.: 62 and CDR-L1, CDR-L2, and CDR-L3 comprise amino acid sequences independently selected from the group consisting of: TABLE-US-00030 CDR-L1 CDR-L2 CDR-L3 residues 24-39 of SEQ ID NO.: 33 residues 55-61 of SEQ ID NO.: 33 residues 94-102 of SEQ ID NO.: 33 residues 24-39 of SEQ ID NO.: 35 residues 55-61 of SEQ ID NO.: 35 residues 94-102 of SEQ ID NO.: 35 residues 24-39 of SEQ ID NO.: 37 residues 55-61 of SEQ ID NO.: 37 residues 94-102 of SEQ ID NO.: 37 residues 24-39 of SEQ ID NO.: 40 residues 55-61 of SEQ ID NO.: 40 residues 94-102 of SEQ ID NO.: 40 residues 24-39 of SEQ ID NO.: 43 residues 55-61 of SEQ ID NO.: 43 residues 94-102 of SEQ ID NO.: 43 residues 24-40 of SEQ ID NO.: 45 residues 56-62 of SEQ ID NO.: 45 residues 95-103 of SEQ ID NO.: 45 residues 24-34 of SEQ ID NO.: 47 residues 50-56 of SEQ ID NO.: 47 residues 89-97 of SEQ ID NO.: 47 residues 24-34 of SEQ ID NO.: 49 residues 50-56 of SEQ ID NO.: 49 residues 89-97 of SEQ ID NO.: 49 residues 24-34 of SEQ ID NO.: 51 residues 50-56 of SEQ ID NO.: 51 residues 89-97 of SEQ ID NO.: 51 residues 23-36 of SEQ ID NO.: 53 residues 52-58 of SEQ ID NO.: 53 residues 91-99 of SEQ ID NO.: 53 residues 24-38 of SEQ ID NO.: 55 residues 54-60 of SEQ ID NO.: 55 residues 93-101 of SEQ ID NO.: 55 residues 24-38 of SEQ ID NO.: 57 residues 54-60 of SEQ ID NO.: 57 residues 93-101 of SEQ ID NO.: 57 residues 24-38 of SEQ ID NO.: 59 residues 54-60 of SEQ ID NO.: 59 residues 93-101 of SEQ ID NO.: 59 residues 24-38 of SEQ ID NO.: 61 residues 54-60 of SEQ ID NO.: 61 residues 93-101 of SEQ ID NO.: 61 residues 24-38 of SEQ ID NO.: 63 residues 54-60 of SEQ ID NO.: 63 residues 93-101 of SEQ ID NO.: 63 residues 24-34 of SEQ ID NO: 92 residues 50-56 of SEQ ID NO: 92 residues 89-97 of SEQ ID NO: 92 residues 24-34 of SEQ ID NO: 93 residues 50-56 of SEQ ID NO: 93 residues 89-97 of SEQ ID NO: 93 residues 24-34 of SEQ ID NO: 94 residues 50-56 of SEQ ID NO: 94 residues 89-97 of SEQ ID NO: 94. wherein said disorder is selected from the group consisting of respiratory disorders; asthma; allergic and nonallergic asthma; asthma due to infection; asthma due to infection with respiratory syncytial virus (RSV); chronic obstructive pulmonary disease (COPD); other conditions involving airway inflammation; eosinophilia; fibrosis and excess mucus production; cystic fibrosis; pulmonary fibrosis; atopic disorders; atopic dermatitis; urticaria; eczema; allergic rhinitis; and allergic enterogastritis; inflammatory and/or autoimmune conditions of the skin; inflammatory and/or autoimmune conditions of gastrointestinal organs; inflammatory bowel diseases (IBD); ulcerative colitis; Crohn's disease; inflammatory and/or autoimmune conditions of the liver; liver cirrhosis; liver fibrosis; liver fibrosis caused by hepatitis B and/or C virus; scleroderma; tumors or cancers; hepatocellular carcinoma; glioblastoma; lymphoma; Hodgkin's lymphoma; viral infections; HTLV-1 infection; suppression of expression of protective type 1 immune responses, and suppression of expression of protective type 1 immune responses during vaccination. 3. The method according to claim 1 or claim 2 wherein the step of administering an IL-13 binding protein is before, concurrent, or after the administration of a second agent, wherein the second agent is selected from the group consisting of inhaled steroids; beta-agonists; short-acting or long-acting beta-agonists; antagonists of leukotrienes or leukotriene receptors; ADVAIR; IgE inhibitors; anti-IgE antibodies; XOLAIR; phosphodiesterase inhibitors; PDE4 inhibitors; xanthines; anticholinergic drugs; mast cell-stabilizing agents; Cromolyn; IL-4 inhibitors; IL-5 inhibitors; eotaxin/CCR3 inhibitors; antagonists of histamine or its receptors including H1, H2, H3, and H4; antagonists of prostaglandin D or its receptors DP1 and CRTH2; TNF antagonists; a soluble fragment of a TNF receptor; ENBREL; TNF enzyme antagonists; TNF converting enzyme (TACE) inhibitors; muscarinic receptor antagonists; TGF-beta antagonists; interferon gamma; perfenidone; chemotherapeutic agents, methotrexate; leflunomide; sirolimus (rapamycin) or an analog thereof, CCI-779; COX2 or cPLA2 inhibitors; NSAIDs; immunomodulators; p38 inhibitors; TPL-2, MK-2 and NFkB inhibitors; budenoside; epidermal growth factor; corticosteroids; cyclosporine; sulfasalazine; aminosalicylates; 6-mercaptopurine; azathioprine; metronidazole; lipoxygenase inhibitors; mesalamine; olsalazine; balsalazide; antioxidants; thromboxane inhibitors; IL-1 receptor antagonists; anti-IL-1.beta. antibodies; anti-IL-6 antibodies; growth factors; elastase inhibitors; pyridinyl-imidazole compounds; antibodies or agonists of TNF, LT, IL-1, 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; antibodies of CD2, CD3, CD4, CD8, CD25, CD28, CD30, CD40, CD45, CD69, CD90 or their ligands; FK506; rapamycin; mycophenolate mofetil; ibuprofen; prednisolone; phosphodiesterase inhibitors; adenosine agonists; antithrombotic agents; complement inhibitors; adrenergic agents; IRAK, NIK, IKK, p38, or MAP kinase inhibitors; IL-1.beta. converting enzyme inhibitors; TNF.alpha. converting enzyme inhibitors; T-cell signaling inhibitors; metalloproteinase inhibitors; 6-mercaptopurines; angiotensin converting enzyme inhibitors; soluble cytokine receptors; soluble p55 TNF receptor; soluble p75 TNF receptor; sIL-1RI; sIL-1RII; sIL-6R; anti-inflammatory cytokines; IL-4; IL-10; IL-11; and TGF.beta.. 4. The method according to claim 1 or claim 2, wherein said administering to the subject is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intraarticular, 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. 5. The method according to claim 1 or claim 2, wherein said binding protein binds human IL-13 and comprises six CDRs, CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1 comprises residues 31-37 of SEQ ID NO:46, CDR-H2 comprises residues 52-67 of SEQ ID NO:46, CDR-H3 comprises residues 100-112 of SEQ ID NO:46, CDR-L1 comprises residue 24-34 of SEQ ID NO:47, CDR-L2 comprises residues 50-56 of SEQ ID NO:47, and CDR-L3 comprises residues 89-97 of SEQ ID NO:47. 6. The method according to claim 5, wherein said binding protein comprises two variable domains, wherein one of the two variable domains comprises the amino acid sequence of SEQ ID NO.:80 and the other of the two variable domains comprises the amino acid sequence of SEQ ID NO.:81. 7. The method according to claim 6, wherein said binding protein comprises four variable domains, wherein each of two of the four variable domains comprises the amino acid sequence of SEQ ID NO:80 and each of the other two of the four variable domains comprises the amino acid sequence of SEQ ID NO:81. 8. The method according to claim 6, wherein said binding protein further comprises a human IgG1 heavy chain constant region comprising a hinge region that comprises a leucine to alanine change at position 234 and a leucine to alanine change at position 235, and a human kappa light chain constant region. 9. The method according to claim 7, wherein said binding protein further comprises a human IgG1 heavy chain constant region comprising a hinge region that comprises a leucine to alanine change at position 234 and a leucine to alanine change at position 235, and a human kappa light chain constant region. 10. The method according to claim 6, wherein said binding protein is capable of binding a human IL-13 having an amino acid sequence of SEQ ID NO:1 and is capable of binding a human IL-13 variant in which an arginine residue at position 130 of SEQ ID NO:1 is replaced with a glutamine residue. 11. The method according to claim 7, wherein said binding protein is capable of binding a human IL-13 having an amino acid sequence of SEQ ID NO:1 and is capable of binding a human IL-13 variant in which an arginine residue at position 130 of SEQ ID NO:1 is replaced with a glutamine residue. 12. The method according to claim 6, wherein said disorder is asthma, eosinophilia, atopic dermatitis, urticaria, or allergic rhinitis. 13. The method according to claim 7, wherein said disorder is asthma, eosinophilia, atopic dermatitis, urticaria, or allergic rhinitis.

Details for Patent 9,592,293

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2026-09-08
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2026-09-08
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2026-09-08