IL-1 Binding Proteins
First Claim
1. A binding protein comprising a variable heavy chain polypeptide comprising having an amino acid sequence selected from the group consisting of SEQ ID No. 37, SEQ ID No. 38, SEQ ID No. 39, SEQ ID No. 40, SEQ ID No. 48, SEQ ID No. 50, SEQ ID No. 52, and SEQ ID No. 54;
- and a variable light chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 41, SEQ ID No. 42, SEQ ID No. 43, SEQ ID No. 44, SEQ ID No. 45, SEQ ID No. 46, SEQ ID No. 47, SEQ ID No. 49, SEQ ID No. 51, SEQ ID No. 53, and SEQ ID No. 55;
wherein said binding protein is capable of binding human IL-1α
.
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Accused Products
Abstract
The present invention encompasses IL-1α binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Antibodies of the invention have high affinity for IL-1α and neutralize IL-1α activity. 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 IL-1α and for inhibiting IL-1α activity, e.g., in a human subject suffering from a disorder in which IL-1α activity is detrimental.
105 Citations
52 Claims
-
1. A binding protein comprising a variable heavy chain polypeptide comprising having an amino acid sequence selected from the group consisting of SEQ ID No. 37, SEQ ID No. 38, SEQ ID No. 39, SEQ ID No. 40, SEQ ID No. 48, SEQ ID No. 50, SEQ ID No. 52, and SEQ ID No. 54;
- and a variable light chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 41, SEQ ID No. 42, SEQ ID No. 43, SEQ ID No. 44, SEQ ID No. 45, SEQ ID No. 46, SEQ ID No. 47, SEQ ID No. 49, SEQ ID No. 51, SEQ ID No. 53, and SEQ ID No. 55;
wherein said binding protein is capable of binding human IL-1α
. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52)
-
2. The binding protein according to claim 1 wherein said binding protein comprises a variable heavy chain polypeptide and a variable light chain polypeptide selected from the group consisting of;
- SEQ ID NO.;
38 &
SEQ ID NO.;
44, SEQ ID NO.;
40 &
SEQ ID NO.;
44, SEQ ID NO.;
48 &
SEQ ID NO.;
49, SEQ ID NO.;
50 &
SEQ ID NO.;
51, SEQ ID NO.;
52 &
SEQ ID NO.;
53, and SEQ ID NO.;
54 &
SEQ ID NO.;
55.
- SEQ ID NO.;
-
3. The binding protein of claim 1, wherein said binding protein is selected from the group consisting of;
- an immunoglobulin molecule, a disulfide linked Fv, a monoclonal antibody, a scFv, a chimeric antibody, a single domain antibody, a CDR-grafted antibody, a diabody, a humanized antibody, a multispecific antibody, a Fab, a dual specific antibody, a DVD, a Fab′
, a bispecific antibody, a F(ab′
)2, and a Fv.
- an immunoglobulin molecule, a disulfide linked Fv, a monoclonal antibody, a scFv, a chimeric antibody, a single domain antibody, a CDR-grafted antibody, a diabody, a humanized antibody, a multispecific antibody, a Fab, a dual specific antibody, a DVD, a Fab′
-
4. The binding protein of claim 1, wherein said binding protein comprises a heavy chain immunoglobulin constant domain selected from the group consisting of;
- a human IgM constant domain, a human IgG4 constant domain, a human IgG1 constant domain, a human IgE constant domain, a human IgG2 constant domain, a human IgG3 constant domain, and a human IgA constant domain.
-
5. The binding protein of claim 1 further comprising a heavy chain constant region having an amino acid sequence selected from the group consisting of SEQ ID No. 2 and SEQ ID No. 3.
-
6. The binding protein of claim 1 further comprising a light chain constant region having an amino acid sequence selected from the group consisting of SEQ ID No. 4 and SEQ ID No. 5.
-
7. The binding protein of claim 1, wherein said binding protein is capable of modulating a biological function of human IL-1α
- .
-
8. The binding protein of claim 1, wherein said binding protein is capable of neutralizing human IL-1α
- .
-
9. The binding protein according to claim 1, wherein said binding protein has an on rate constant (Kon) to said target selected from the group consisting of:
- at least about 102M−
1 s−
1;
at least about 103M−
1 s−
1;
at least about 104M−
1 s−
1;
at least about 105M−
1 s−
1; and
at least about 106M−
1 s−
1 as measured by surface plasmon resonance.
- at least about 102M−
-
10. The binding protein according to claim 1, wherein said binding protein has an off rate constant (Koff) to said target selected from the group consisting of:
- at most about 10−
3 s−
1;
at most about 10−
4 s−
1;
at most about 10−
5 s−
1; and
at most about 10−
6 s−
1, as measured by surface plasmon resonance.
- at most about 10−
-
11. The binding protein according to claim 1, wherein said binding protein has a dissociation constant (KD) to said target selected from the group consisting of:
- at most about 10−
7 M;
at most about 10−
8 M;
at most about 10−
9 M;
at most about 10−
10 M;
at most about 10−
11 M;
at most about 10−
12 M; and
at most 10−
13M.
- at most about 10−
-
12. The binding protein according to claim 11, wherein said binding protein has a dissociation constant (KD) to IL-1α
- selected from the group consisting of;
1.34×
10−
9M;
1.35×
10−
9M;
2.09×
10−
9M;
2.8×
10−
11 M;
1×
10−
11 M;
3.1×
10−
11 M;
3.2×
10−
11 M; and
3.3×
10−
11 M.
- selected from the group consisting of;
-
13. The binding protein according to claim 1, wherein said binding protein further comprises an agent selected from the group consisting of;
- an immunoadhension molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.
-
14. The binding protein according to claim 13, wherein said agent is an imaging agent selected from the group consisting of a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, and biotin.
-
15. The binding protein according to claim 13, wherein said imaging agent is a radiolabel selected from the group consisting of:
- 3H, 14C, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, and 153Sm.
-
16. The binding protein according to claim 13, wherein said agent is a therapeutic or cytotoxic agent selected from the group consisting of;
- an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, and an apoptotic agent.
-
17. The binding protein according to claim 1, wherein said binding protein possesses a human glycosylation pattern.
-
18. The binding protein according to claim 1, wherein said binding protein is a crystallized binding protein.
-
19. The binding protein according to claim 18, wherein said crystallized binding protein is a carrier-free pharmaceutical controlled release crystallized binding protein.
-
20. The binding protein according to claim 19, wherein said binding protein has a greater half life in vivo than the soluble counterpart of said antibody construct.
-
21. The binding protein according to claim 19, wherein said binding protein retains biological activity.
-
22. An isolated nucleic acid encoding a binding protein amino acid sequence described in claim 1.
-
23. A vector comprising an isolated nucleic acid encoding a binding protein amino acid sequence described in claim 1.
-
24. The vector of claim 23 wherein said vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pJV, and pBJ.
-
25. A host cell comprising a vector described in claim 23.
-
26. The host cell according to claim 25, wherein said host cell is a prokaryotic cell.
-
27. The host cell according to claim 26, wherein said host cell is E. Coli.
-
28. The host cell according to claim 25, wherein said host cell is a eukaryotic cell.
-
29. The host cell according to claim 28, wherein said eukaryotic cell is selected from the group consisting of protist cell, animal cell, plant cell and fungal cell.
-
30. The host cell according to claim 28, wherein said eukaryotic cell is an animal cell selected from the group consisting of;
- a mammalian cell, an avian cell, and an insect cell.
-
31. The host cell according to claim 28, wherein said host cell is a CHO cell.
-
32. The host cell according to claim 28, wherein said host cell is COS.
-
33. The host cell according to claim 28, wherein said host cell is a yeast cell.
-
34. The host cell according to claim 33, wherein said yeast cell is Saccharomyces cerevisiae.
-
35. The host cell according to claim 28, wherein said host cell is an insect Sf9 cell.
-
36. A method of producing a protein capable of binding IL-1α
- , comprising culturing a host cell described in claim 25 in culture medium under conditions sufficient to produce a binding protein capable of binding IL-1α
.
- , comprising culturing a host cell described in claim 25 in culture medium under conditions sufficient to produce a binding protein capable of binding IL-1α
-
37. A protein produced according to the method of claim 36.
-
38. A composition for the release of a binding protein said composition comprising:
-
(a) a formulation, wherein said formulation comprises a crystallized binding protein, described in claim 16, and an ingredient; and (b) at least one polymeric carrier.
-
-
39. The composition according to claim 38, wherein said polymeric carrier is a polymer selected from one or more of the group consisting of:
- poly (acrylic acid), poly (cyanoacrylates), poly (amino acids), poly (anhydrides), poly (depsipeptide), poly (esters), poly (lactic acid), poly (lactic-co-glycolic acid) or PLGA, poly (b-hydroxybutryate), poly (caprolactone), poly (dioxanone);
poly (ethylene glycol), poly ((hydroxypropyl)methacrylamide, poly [(organo) phosphazene], poly (ortho esters), poly (vinyl alcohol), poly (vinylpyrrolidone), maleic anhydride-alkyl vinyl ether copolymers, pluronic polyols, albumin, alginate, cellulose and cellulose derivatives, collagen, fibrin, gelatin, hyaluronic acid, oligosaccharides, glycaminoglycans, sulfated polyeaccharides, blends and copolymers thereof.
- poly (acrylic acid), poly (cyanoacrylates), poly (amino acids), poly (anhydrides), poly (depsipeptide), poly (esters), poly (lactic acid), poly (lactic-co-glycolic acid) or PLGA, poly (b-hydroxybutryate), poly (caprolactone), poly (dioxanone);
-
40. The composition according to claim 38, wherein said ingredient is selected from the group consisting of albumin, sucrose, trehalose, lactitol, gelatin, hydroxypropyl-β
- -cyclodextrin, methoxypolyethylene glycol and polyethylene glycol.
-
41. A method for treating a mammal comprising the step of administering to the mammal an effective amount of the composition described in claim 38.
-
42. A pharmaceutical composition comprising the binding protein of claim 1, and a pharmaceutically acceptable carrier.
-
43. The pharmaceutical composition of claim 42 wherein said pharmaceutically acceptable carrier functions as adjuvant useful to increase the absorption, or dispersion of said binding protein.
-
44. The pharmaceutical composition of claim 43 wherein said adjuvant is hyaluronidase.
-
45. The pharmaceutical composition of claim 42 further comprising at least one additional therapeutic agent for treating a disorder in which IL-1α
- activity is detrimental.
-
46. The pharmaceutical composition of claim 45, wherein said additional agent is selected from the group consisting of:
- Therapeutic agent, imaging agent, cytotoxic agent, angiogenesis inhibitors;
kinase inhibitors;
co-stimulation molecule blockers;
adhesion molecule blockers;
anti-cytokine antibody or functional fragment thereof;
methotrexate;
cyclosporin;
rapamycin;
FK506;
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 corticosteriod, 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.
- Therapeutic agent, imaging agent, cytotoxic agent, angiogenesis inhibitors;
-
47. A method for reducing human IL-1α
- activity comprising contacting human IL-1α
with the binding protein of claim 1 such that human IL-1α
activity is reduced.
- activity comprising contacting human IL-1α
-
48. A method for reducing human IL-1α
- activity in a human subject suffering from a disorder in which IL-1α
activity is detrimental, comprising administering to the human subject the binding protein of claim 1 such that human IL-1α
activity in the human subject is reduced.
- activity in a human subject suffering from a disorder in which IL-1α
-
49. A method for treating a subject for a disease or a disorder in which IL-1α
- activity is detrimental by administering to the subject the binding protein of claim 1 such that treatment is achieved.
-
50. The method of claim 49, wherein said disorder is selected from the group consisting of rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, septic arthritis, Lyme arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, systemic lupus erythematosus, Crohn'"'"'s disease, ulcerative colitis, inflammatory bowel disease, insulin dependent diabetes mellitus, thyroiditis, asthma, allergic diseases, psoriasis, dermatitis scleroderma, graft versus host disease, organ transplant rejection, acute or chronic immune disease associated with organ transplantation, sarcoidosis, atherosclerosis, disseminated intravascular coagulation, Kawasaki'"'"'s disease, Grave'"'"'s disease, nephrotic syndrome, chronic fatigue syndrome, Wegener'"'"'s granulomatosis, Henoch-Schoenlein purpurea, microscopic vasculitis of the kidneys, chronic active hepatitis, uveitis, septic shock, toxic shock syndrome, sepsis syndrome, cachexia, infectious diseases, parasitic diseases, acquired immunodeficiency syndrome, acute transverse myelitis, Huntington'"'"'s chorea, Parkinson'"'"'s disease, Alzheimer'"'"'s disease, stroke, primary biliary cirrhosis, hemolytic anemia, malignancies, heart failure, myocardial infarction, Addison'"'"'s disease, sporadic, polyglandular deficiency type I and polyglandular deficiency type II, Schmidt'"'"'s syndrome, adult (acute) respiratory distress syndrome, alopecia, alopecia areata, seronegative arthopathy, arthropathy, Reiter'"'"'s disease, psoriatic arthropathy, ulcerative colitic arthropathy, enteropathic synovitis, chlamydia, yersinia and salmonella associated arthropathy, spondyloarthopathy, atheromatous disease/arteriosclerosis, atopic allergy, autoimmune bullous disease, pemphigus vulgaris, pemphigus foliaceus, pemphigoid, linear IgA disease, autoimmune haemolytic anaemia, Coombs positive haemolytic anaemia, acquired pernicious anaemia, juvenile pernicious anaemia, myalgic encephalitis/Royal Free Disease, chronic mucocutaneous candidiasis, giant cell arteritis, primary sclerosing hepatitis, cryptogenic autoimmune hepatitis, Acquired Immunodeficiency Disease Syndrome, Acquired Immunodeficiency Related Diseases, Hepatitis B, Hepatitis C, common varied immunodeficiency (common variable hypogammaglobulinaemia), dilated cardiomyopathy, female infertility, ovarian failure, premature ovarian failure, fibrotic lung disease, cryptogenic fibrosing alveolitis, post-inflammatory interstitial lung disease, interstitial pneumonitis, connective tissue disease associated interstitial lung disease, mixed connective tissue disease associated lung disease, systemic sclerosis associated interstitial lung disease, rheumatoid arthritis associated interstitial lung disease, systemic lupus erythematosus associated lung disease, dermatomyositis/polymyositis associated lung disease, Sjö
- gren'"'"'s disease associated lung disease, ankylosing spondylitis associated lung disease, vasculitic diffuse lung disease, haemosiderosis associated lung disease, drug-induced interstitial lung disease, fibrosis, radiation fibrosis, bronchiolitis obliterans, chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease, postinfectious interstitial lung disease, gouty arthritis, autoimmune hepatitis, type-1 autoimmune hepatitis (classical autoimmune or lupoid hepatitis), type-2 autoimmune hepatitis (anti-LKM antibody hepatitis), autoimmune mediated hypoglycaemia, type B insulin resistance with acanthosis nigricans, hypoparathyroidism, acute immune disease associated with organ transplantation, chronic immune disease associated with organ transplantation, osteoarthrosis, primary sclerosing cholangitis, psoriasis type 1, psoriasis type 2, idiopathic leucopaenia, autoimmune neutropaenia, renal disease NOS, glomerulonephritides, microscopic vasulitis of the kidneys, lyme disease, discoid lupus erythematosus, male infertility idiopathic or NOS, sperm autoimmunity, multiple sclerosis (all subtypes), sympathetic ophthalmia, pulmonary hypertension secondary to connective tissue disease, Goodpasture'"'"'s syndrome, pulmonary manifestation of polyarteritis nodosa, acute rheumatic fever, rheumatoid spondylitis, Still'"'"'s disease, systemic sclerosis, Sjö
rgren'"'"'s syndrome, Takayasu'"'"'s disease/arteritis, autoimmune thrombocytopaenia, idiopathic thrombocytopaenia, autoimmune thyroid disease, hyperthyroidism, goitrous autoimmune hypothyroidism (Hashimoto'"'"'s disease), atrophic autoimmune hypothyroidism, primary myxoedema, phacogenic uveitis, primary vasculitis, vitiligo acute liver disease, chronic liver diseases, alcoholic cirrhosis, alcohol-induced liver injury, choleosatatis, idiosyncratic liver disease, Drug-Induced hepatitis, Non-alcoholic Steatohepatitis, allergy and asthma, group B streptococci (GBS) infection, mental disorders (e.g., depression and schizophrenia), Th2 Type and Th1 Type mediated diseases, acute and chronic pain (different forms of pain), and cancers such as lung, breast, stomach, bladder, colon, pancreas, ovarian, prostate and rectal cancer and hematopoietic malignancies (leukemia and lymphoma), Abetalipoprotemia, Acrocyanosis, acute and chronic parasitic or infectious processes, acute leukemia, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), acute or chronic bacterial infection, acute pancreatitis, acute renal failure, adenocarcinomas, aerial ectopic beats, AIDS dementia complex, alcohol-induced hepatitis, allergic conjunctivitis, allergic contact dermatitis, allergic rhinitis, allograft rejection, alpha-1-antitrypsin deficiency, amyotrophic lateral sclerosis, anemia, angina pectoris, anterior horn cell degeneration, anti cd3 therapy, antiphospholipid syndrome, anti-receptor hypersensitivity reactions, aordic and peripheral aneuryisms, aortic dissection, arterial hypertension, arteriosclerosis, arteriovenous fistula, ataxia, atrial fibrillation (sustained or paroxysmal), atrial flutter, atrioventricular block, B cell lymphoma, bone graft rejection, bone marrow transplant (BMT) rejection, bundle branch block, Burkitt'"'"'s lymphoma, Burns, cardiac arrhythmias, cardiac stun syndrome, cardiac tumors, cardiomyopathy, cardiopulmonary bypass inflammation response, cartilage transplant rejection, cerebellar cortical degenerations, cerebellar disorders, chaotic or multifocal atrial tachycardia, chemotherapy associated disorders, chromic myelocytic leukemia (CML), chronic alcoholism, chronic inflammatory pathologies, chronic lymphocytic leukemia (CLL), chronic obstructive pulmonary disease (COPD), chronic salicylate intoxication, colorectal carcinoma, congestive heart failure, conjunctivitis, contact dermatitis, cor pulmonale, coronary artery disease, Creutzfeldt-Jakob disease, culture negative sepsis, cystic fibrosis, cytokine therapy associated disorders, Dementia pugilistica, demyelinating diseases, dengue hemorrhagic fever, dermatitis, dermatologic conditions, diabetes, diabetes mellitus, diabetic ateriosclerotic disease, Diffuse Lewy body disease, dilated congestive cardiomyopathy, disorders of the basal ganglia, Down'"'"'s Syndrome in middle age, drug-induced movement disorders induced by drugs which block CNS dopamine receptors, drug sensitivity, eczema, encephalomyelitis, endocarditis, endocrinopathy, epiglottitis, epstein-barr virus infection, erythromelalgia, extrapyramidal and cerebellar disorders, familial hematophagocytic lymphohistiocytosis, fetal thymus implant rejection, Friedreich'"'"'s ataxia, functional peripheral arterial disorders, fungal sepsis, gas gangrene, gastric ulcer, glomerular nephritis, graft rejection of any organ or tissue, gram negative sepsis, gram positive sepsis, granulomas due to intracellular organisms, hairy cell leukemia, Hallerrorden-Spatz disease, hashimoto'"'"'s thyroiditis, hay fever, heart transplant rejection, hemachromatosis, hemodialysis, hemolytic uremic syndrome/thrombolytic thrombocytopenic purpura, hemorrhage, hepatitis (A), His bundle arrythmias, HIV infection/HIV neuropathy, Hodgkin'"'"'s disease, hyperkinetic movement disorders, hypersensitity reactions, hypersensitivity pneumonitis, hypertension, hypokinetic movement disorders, hypothalamic-pituitary-adrenal axis evaluation, idiopathic Addison'"'"'s disease, idiopathic pulmonary fibrosis, antibody mediated cytotoxicity, Asthenia, infantile spinal muscular atrophy, inflammation of the aorta, influenza a, ionizing radiation exposure, iridocyclitis/uveitis/optic neuritis, ischemia-reperfusion injury, ischemic stroke, juvenile rheumatoid arthritis, juvenile spinal muscular atrophy, Kaposi'"'"'s sarcoma, kidney transplant rejection, legionella, leishmaniasis, leprosy, lesions of the corticospinal system, lipedema, liver transplant rejection, lymphederma, malaria, malignamt Lymphoma, malignant histiocytosis, malignant melanoma, meningitis, meningococcemia, metabolic/idiopathic, migraine headache, mitochondrial multi.system disorder, mixed connective tissue disease, monoclonal gammopathy, multiple myeloma, multiple systems degenerations (Mencel Dejerine-Thomas Shi-Drager and Machado-Joseph), myasthenia gravis, mycobacterium avium intracellulare, mycobacterium tuberculosis, myelodyplastic syndrome, myocardial infarction, myocardial ischemic disorders, nasopharyngeal carcinoma, neonatal chronic lung disease, nephritis, nephrosis, neurodegenerative diseases, neurogenic I muscular atrophies, neutropenic fever, non-hodgkins lymphoma, occlusion of the abdominal aorta and its branches, occulsive arterial disorders, okt3 therapy, orchitis/epidydimitis, orchitis/vasectomy reversal procedures, organomegaly, osteoporosis, pancreas transplant rejection, pancreatic carcinoma, paraneoplastic syndrome/hypercalcemia of malignancy, parathyroid transplant rejection, pelvic inflammatory disease, perennial rhinitis, pericardial disease, peripheral atherlosclerotic disease, peripheral vascular disorders, peritonitis, pernicious anemia, pneumocystis carinii pneumonia, pneumonia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome), post perfusion syndrome, post pump syndrome, post-MI cardiotomy syndrome, preeclampsia, Progressive supranucleo Palsy, primary pulmonary hypertension, radiation therapy, Raynaud'"'"'s phenomenon and disease, Raynoud'"'"'s disease, Refsum'"'"'s disease, regular narrow QRS tachycardia, renovascular hypertension, reperfusion injury, restrictive cardiomyopathy, sarcomas, scleroderma, senile chorea, Senile Dementia of Lewy body type, seronegative arthropathies, shock, sickle cell anemia, skin allograft rejection, skin changes syndrome, small bowel transplant rejection, solid tumors, specific arrythmias, spinal ataxia, spinocerebellar degenerations, streptococcal myositis, structural lesions of the cerebellum, Subacute sclerosing panencephalitis, Syncope, syphilis of the cardiovascular system, systemic anaphalaxis, systemic inflammatory response syndrome, systemic onset juvenile rheumatoid arthritis, T-cell or FAB ALL, Telangiectasia, thromboangitis obliterans, thrombocytopenia, toxicity, transplants, trauma/hemorrhage, type III hypersensitivity reactions, type IV hypersensitivity, unstable angina, uremia, urosepsis, urticaria, valvular heart diseases, varicose veins, vasculitis, venous diseases, venous thrombosis, ventricular fibrillation, viral and fungal infections, vital encephalitis/aseptic meningitis, vital-associated hemaphagocytic syndrome, Wernicke-Korsakoff syndrome, Wilson'"'"'s disease, xenograft rejection of any organ or tissue, Acute coronary syndromes, Acute Idiopathic Polyneuritis, Acute Inflammatory Demyelinating Polyradiculoneuropathy, Acute ischemia, Adult Still'"'"'s Disease, Alopecia areata, Anaphylaxis, Anti-Phospholipid Antibody Syndrome, Aplastic anemia, Arteriosclerosis, Atopic eczema, Atopic dermatitis, Autoimmune dermatitis, Autoimmune disorder associated with Streptococcus infection, Autoimmune Enteropathy, Autoimmune hearingloss, Autoimmune Lymphoproliferative Syndrome (ALPS), Autoimmune myocarditis, Autoimmune premature ovarian failure, Blepharitis, Bronchiectasis, Bullous pemphigoid, Cardiovascular Disease, Catastrophic Antiphospholipid Syndrome, Celiac Disease, Cervical Spondylosis, Chronic ischemia, Cicatricial pemphigoid, Clinically isolated Syndrome (CIS) with Risk for Multiple Sclerosis, Conjunctivitis, Childhood Onset Psychiatric Disorder, Chronic obstructive pulmonary disease (COPD), Dacryocystitis, dermatomyositis, Diabetic retinopathy, Diabetes mellitus, Disk herniation, Disk prolaps, Drug induced immune hemolytic anemia, Endocarditis, Endometriosis, endophthalmitis, Episcleritis, Erythema multiforme, erythema multiforme major, Gestational pemphigoid, Guillain-Barre Syndrome (GBS), Hay Fever, Hughes Syndrome, Idiopathic Parkinson'"'"'s Disease, idiopathic interstitial pneumonia, IgE-mediated Allergy, Immune hemolytic anemia, Inclusion Body Myositis, Infectious ocular inflammatory disease, Inflammatory demyelinating disease, Inflammatory heart disease, Inflammatory kidney disease, IPF/UIP, Iritis, Keratitis, Keratojuntivitis sicca, Kussmaul disease or Kussmaul-Meier Disease, Landry'"'"'s Paralysis, Langerhan'"'"'s Cell Histiocytosis, Livedo reticularis, Macular Degeneration, Microscopic Polyangiitis, Morbus Bechterev, Motor Neuron Disorders, Mucous membrane pemphigoid, Multiple Organ failure, Myasthenia Gravis, Myelodysplastic Syndrome, Myocarditis, Nerve Root Disorders, Neuropathy, Non-A Non-B Hepatitis, Optic Neuritis, Osteolysis, Pauciarticular JRA, peripheral artery occlusive disease (PAOD), peripheral vascular disease (PVD), peripheral artery disease (PAD), Phlebitis, Polyarteritis nodosa (or periarteritis nodosa), Polychondritis, Polymyalgia Rheumatica, Poliosis, Polyarticular JRA, Polyendocrine Deficiency Syndrome, Polymyositis, polymyalgia rheumatica (PMR), Post-Pump Syndrome, primary parkinsonism, Prostatitis, Pure red cell aplasia, Primary Adrenal Insufficiency, Recurrent Neuromyelitis Optica, Restenosis, Rheumatic heart disease, SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis), Scleroderma, Secondary Amyloidosis, Shock lung, Scleritis, Sciatica, Secondary Adrenal Insufficiency, Silicone associated connective tissue disease, Sneddon-Wilkinson Dermatosis, spondilitis ankylosans, Stevens-Johnson Syndrome (SJS), Systemic inflammatory response syndrome, Temporal arteritis, toxoplasmic retinitis, toxic epidermal necrolysis, Transverse myelitis, TRAPS (Tumor Necrosis Factor Receptor, Type 1 allergic reaction, Type II Diabetes, Urticaria, Usual interstitial pneumonia (UIP), Vasculitis, Vernal conjunctivitis, viral retinitis, Vogt-Koyanagi-Harada syndrome (VKH syndrome), Wet macular degeneration, and Wound healing.
- gren'"'"'s disease associated lung disease, ankylosing spondylitis associated lung disease, vasculitic diffuse lung disease, haemosiderosis associated lung disease, drug-induced interstitial lung disease, fibrosis, radiation fibrosis, bronchiolitis obliterans, chronic eosinophilic pneumonia, lymphocytic infiltrative lung disease, postinfectious interstitial lung disease, gouty arthritis, autoimmune hepatitis, type-1 autoimmune hepatitis (classical autoimmune or lupoid hepatitis), type-2 autoimmune hepatitis (anti-LKM antibody hepatitis), autoimmune mediated hypoglycaemia, type B insulin resistance with acanthosis nigricans, hypoparathyroidism, acute immune disease associated with organ transplantation, chronic immune disease associated with organ transplantation, osteoarthrosis, primary sclerosing cholangitis, psoriasis type 1, psoriasis type 2, idiopathic leucopaenia, autoimmune neutropaenia, renal disease NOS, glomerulonephritides, microscopic vasulitis of the kidneys, lyme disease, discoid lupus erythematosus, male infertility idiopathic or NOS, sperm autoimmunity, multiple sclerosis (all subtypes), sympathetic ophthalmia, pulmonary hypertension secondary to connective tissue disease, Goodpasture'"'"'s syndrome, pulmonary manifestation of polyarteritis nodosa, acute rheumatic fever, rheumatoid spondylitis, Still'"'"'s disease, systemic sclerosis, Sjö
-
51. A method of treating a patient suffering from a disorder in which IL-1α
- is detrimental comprising the step of administering the binding protein of claim 1 before, concurrent, or after the administration of a second agent, wherein the second agent is selected from the group consisting of 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-1β
, 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;
adensosine 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
.
- is detrimental comprising the step of administering the binding protein of claim 1 before, concurrent, or after the administration of a second agent, wherein the second agent is selected from the group consisting of TNF antagonists;
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52. The method according to claim 49, wherein said administering to the subject is by at least one mode selected from parenteral, subcutaneous, intramuscular, intravenous, intrarticular, 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.
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2. The binding protein according to claim 1 wherein said binding protein comprises a variable heavy chain polypeptide and a variable light chain polypeptide selected from the group consisting of;
- and a variable light chain polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 41, SEQ ID No. 42, SEQ ID No. 43, SEQ ID No. 44, SEQ ID No. 45, SEQ ID No. 46, SEQ ID No. 47, SEQ ID No. 49, SEQ ID No. 51, SEQ ID No. 53, and SEQ ID No. 55;
Specification
- Resources
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Current AssigneeAbbvie Incorporated
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Original AssigneeAbbott Laboratories Incorporated
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InventorsWu, Chengbin, Hsieh, Chung-ming
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Granted Patent
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Time in Patent OfficeDays
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Field of Search
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US Class Current424/1.490
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CPC Class CodesA61K 38/00 Medicinal preparations cont...A61K 39/3955 against proteinaceous mater...A61K 45/06 Mixtures of active ingredie...A61K 47/6845 the antibody targeting a cy...A61P 1/04 for ulcers, gastritis or re...A61P 1/16 for liver or gallbladder di...A61P 1/18 for pancreatic disorders, e...A61P 11/00 Drugs for disorders of the ...A61P 11/02 Nasal agents, e.g. deconges...A61P 11/06 AntiasthmaticsA61P 13/00 Drugs for disorders of the ...A61P 13/08 of the prostateA61P 13/12 of the kidneysA61P 15/08 for gonadal disorders or fo...A61P 17/00 Drugs for dermatological di...A61P 17/02 for treating wounds, ulcers...A61P 17/04 AntipruriticsA61P 17/06 AntipsoriaticsA61P 17/14 for baldness or alopeciaA61P 19/02 for joint disorders, e.g. a...A61P 19/10 : for osteoporosisA61P 21/00 : Drugs for disorders of the ...A61P 21/02 : Muscle relaxants, e.g. for ...A61P 21/04 : for myasthenia gravisA61P 25/00 : Drugs for disorders of the ...A61P 25/06 : Antimigraine agentsA61P 25/14 : for treating abnormal movem...A61P 25/16 : Anti-Parkinson drugsA61P 25/18 : Antipsychotics, i.e. neurol...A61P 25/24 : AntidepressantsA61P 25/28 : for treating neurodegenerat...A61P 25/32 : Alcohol-abuseA61P 27/02 : Ophthalmic agentsA61P 27/16 : OtologicalsA61P 29/00 : Non-central analgesic, anti...A61P 3/10 : for hyperglycaemia, e.g. an...A61P 3/14 : for calcium homeostasis vit...A61P 31/00 : Antiinfectives, i.e. antibi...A61P 31/04 : Antibacterial agentsA61P 31/10 : AntimycoticsA61P 31/12 : AntiviralsA61P 31/20 : for DNA virusesA61P 33/00 : Antiparasitic agentsA61P 33/02 : Antiprotozoals, e.g. for le...A61P 33/06 : AntimalarialsA61P 35/00 : Antineoplastic agentsA61P 35/02 : specific for leukemiaA61P 37/02 : ImmunomodulatorsA61P 37/06 : Immunosuppressants, e.g. dr...A61P 37/08 : Antiallergic agents antiast...A61P 7/00 : Drugs for disorders of the ...A61P 7/02 : Antithrombotic agents; Anti...A61P 7/04 : Antihaemorrhagics; Procoagu...A61P 7/06 : AntianaemicsA61P 9/00 : Drugs for disorders of the ...A61P 9/04 : Inotropic agents, i.e. stim...A61P 9/06 : AntiarrhythmicsA61P 9/08 : Vasodilators for multiple i...A61P 9/10 : for treating ischaemic or a...A61P 9/12 : AntihypertensivesC07K 16/245 : IL-1C07K 2317/24 : containing regions, domains...C07K 2317/565 : Complementarity determining...C07K 2317/76 : Antagonist effect on antige...C07K 2317/92 : Affinity (KD), association ...Y02A 50/30 : Against vector-borne diseas...