Interleukin-13 binding proteins

1. A recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, wherein said recombinant anti-IL-13 antibody:

binds human IL-13;

comprises two variable domains, wherein one variable domain comprises the amino acid sequence of SEQ ID NO:80 and the other variable domain comprises the amino acid sequence of SEQ ID NO:81;

comprises a human IgG1 heavy chain constant region comprising a hinge region comprising a leucine to alanine change at position 234 and a leucine to alanine change at position 235;

comprises a human kappa light chain constant region;

blocks IL-13 binding to IL-13Rα1 and to IL-13Rα2; and

binds a human IL-13 variant in which an arginine residue at position 130 of SEQ ID NO:1 is replaced with a glutamine residue.

2. The recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, according to claim 1 , wherein said recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, comprises four variable domains, wherein each of two of the variable domains comprises the amino acid sequence of SEQ ID NO:80 and each of the other two of the variable domains comprises the amino acid sequence of SEQ ID NO:81.

3. A pharmaceutical composition comprising a recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, according to claim 1 or claim 2 , and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition according to claim 3 , further comprising at least one additional agent, wherein said agent is selected from the group consisting of: a therapeutic agent, an imaging agent, a cytotoxic agent, an angiogenesis inhibitor, a kinase inhibitor, a co-stimulation molecule blocker, an adhesion molecule blocker, an anti-cytokine antibody or functional fragment thereof; methotrexate, a cyclosporin, a rapamycin, an FK506, a detectable label or reporter, a TNF antagonist, an anti-rheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteroid, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an oral steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist.

5. The pharmaceutical composition according to claim 3 , wherein said pharmaceutical composition is administered by at least one mode selected from the group consisting of: 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.

6. A method for reducing human IL-13 activity in a human subject suffering from a disorder in which IL-13 activity is detrimental, comprising the step of administering to the human subject a recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, wherein said recombinant anti-IL-13 antibody:

binds human IL-13;

comprises two variable domains, wherein one variable domain comprises the amino acid sequence of SEQ ID NO:80 and the other variable domain comprises the amino acid sequence of SEQ ID NO:81;

comprises a human IgG1 heavy chain constant region comprising a hinge region comprising a leucine to alanine change at position 234 and a leucine to alanine change at position 235;

comprises a human kappa light chain constant region;

blocks IL-13 binding to IL-13Rα1 and to IL-13Rα2; and

binds a human IL-13 variant in which an arginine residue at position 130 of SEQ ID NO:1 is replaced with a glutamine residue;

such that human IL-13 activity in the human subject is reduced, and wherein said disorder is selected from the group consisting of: asthma, eosinophilia, atopic dermatitis, urticaria, and allergic rhinitis.

7. The method according to claim 6 , wherein said recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, comprises four variable domains, wherein each of two of the variable domains comprises the amino acid sequence of SEQ ID NO:80 and each of the other two of the variable domains comprises the amino acid sequence of SEQ ID NO:81.

8. A method for treating a human subject for a disorder in which IL-13 activity is detrimental comprising the step of administering to the human subject a recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, wherein said recombinant anti-IL-13 antibody:

binds human IL-13;

comprises two variable domains, wherein one variable domain comprises the amino acid sequence of SEQ ID NO:80 and the other variable domain comprises the amino acid sequence of SEQ ID NO:81;

comprises a human IgG1 heavy chain constant region comprising a hinge region comprising a leucine to alanine change at position 234 and a leucine to alanine change at position 235;

comprises a human kappa light chain constant region;

blocks IL-13 binding to IL-13Rα1 and to IL-13Rα2; and

binds a human IL-13 variant in which an arginine residue at position 130 of SEQ ID NO:1 is replaced with a glutamine residue;

such that treatment is achieved, and wherein said disorder is selected from the group consisting of: asthma, eosinophilia, atopic dermatitis, urticaria, and allergic rhinitis.

9. The method according to claim 8 , wherein said recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, comprises four variable domains, wherein each of two of the variable domains comprises the amino acid sequence of SEQ ID NO:80 and each of the other two of the variable domains comprises the amino acid sequence of SEQ ID NO:81.

10. The method according to any one of claims 6 - 9 , wherein the step of administering the recombinant anti-IL-13 antibody, or antigen binding fragment thereof, is before, concurrently, 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-1β 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-1β converting enzyme inhibitors; TNFα 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 TGFβ.

11. The method according to any one of claims 6 - 9 , wherein said step of administering to the human subject a recombinant anti-IL-13 antibody, or antigen-binding fragment thereof, is by at least one mode selected from the group consisting of: 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.