Dual variable domain immunoglobulins and uses thereof

• US 9,493,560 B2
• Filed: 12/19/2013
• Issued: 11/15/2016
• Est. Priority Date: 08/03/2010
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Ghayur, Tariq, Liu, Junjian, Isakson, Peter C.
• Primary Examiner(s): DAHLE, CHUN WU
• Application Number:
  US14/135,107
• Publication Number:
  US 20140234208A1
• Time in Patent Office: 1,062 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6845 the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 51/1021 against cytokines, e.g. growth factors, VEGF, TNF, lymphokines or interferons
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 : Antipruritics
• CPC Class Codes: A61P 17/06 : Antipsoriatics
• CPC Class Codes: A61P 17/14 : for baldness or alopecia
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/14 : for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 : Antidepressants
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 25/32 : Alcohol-abuse
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/16 : Otologicals
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/245 : IL-1
• CPC Class Codes: C07K 16/468 : Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/33 : Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/35 : Valency
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: G01N 2333/525 : Tumor necrosis factor [TNF]
• CPC Class Codes: G01N 2333/54 : Interleukins [IL]
• CPC Class Codes: G01N 2333/545 : IL-1
• CPC Class Codes: G01N 2800/24 : Immunology or allergic disorders SLE G01N2800/104
• CPC Class Codes: G01N 2800/7028 : Cancer
• CPC Class Codes: G01N 33/53 : Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/56966 : Animal cells
• CPC Class Codes: G01N 33/6857 : Antibody fragments
• CPC Class Codes: G01N 33/6863 : Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/6869 : Interleukin

Abstract

Engineered multivalent and multispecific binding proteins, methods of making, and their uses in the prevention, diagnosis, and/or treatment of disease are provided.

Claims

1. A method for treating a subject for a disease or a disorder in which the activity of IL-17 is detrimental, comprising administering to the subject a binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first variable domain;

VD2 is a second variable domain;

C is a constant domain;

X1 is a linker;

X2 is an Fc region;

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site,

(a) wherein the binding protein is capable of binding IL-17, and wherein the variable domains that form a functional target binding site for IL-17 comprise CDRs 1-3 from SEQ ID NO;

40 and CDRs 1-3 from SEQ ID NO;

41;

(b) wherein the binding protein is also capable of binding IL-1β

or TNFα

; and

(c) wherein the disease or disorder is selected from the group consisting of rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, septic arthritis, Lyme arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, spondilitis anklyosans, systemic lupus erythematosus, Crohn'"'"'s disease, ulcerative colitis, inflammatory bowel disease, psoriasis, sarcoidosis, uveitis, atopic eczema, scleroderma, and amyotrophic lateral sclerosis.

2. The method of claim 1, wherein the binding protein is administered parenterally, subcutaneously, intramuscularly, intravenously, intrarticularly, intrabronchially, intraabdominally, intracapsularly, intracartilaginously, intracavitarily, intracelially, intracerebellarly, intracerebroventricularly, intracolically, intracervically, intragastrically, intrahepatically, intramyocardially, intraosteally, intrapelvically, intrapericardially, intraperitoneally, intrapleurally, intraprostatically, intrapulmonarily, intrarectally, intrarenally, intraretinally, intraspinally, intrasynovially, intrathoracically intrauterine, intravesically, bolusly, vaginally, rectally, buccally, sublingually, intranasally, or transdermally.

3. The method of claim 1, wherein the variable domains that form a functional target binding site for IL-17 comprise SEQ ID NO:

40 and SEQ ID NO;

41.

4. The method of claim 1, wherein

(a) X1 comprises any one of SEQ ID NOs:

1-29;

(b) the binding protein is a crystallized binding protein;

(c) the Fc region is a variant sequence Fc region;

(d) the Fc region is from an IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, or IgD; and

/or

(e) the binding protein comprises two first polypeptide chains and two second polypeptide chains and four functional target binding sites.

5. The method of claim 1, wherein the binding protein is capable of binding TNFα

.

6. A method for treating a subject for a disease or a disorder in which the activity of IL-17 is detrimental, comprising administering to the subject a binding protein comprising first and second polypeptide chains;

each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first variable domain;

VD2 is a second variable domain;

C is a constant domain;

X1 is a linker;

X2 is an Fc region;

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, wherein the binding protein is capable of binding IL-17 and TNFα

, wherein

(a) the variable domains that form a functional target binding site for IL-17 comprise SEQ ID NO;

40 and SEQ ID NO;

41;

(b) X1 comprises SEQ ID NO;

29 on the first and second polypeptide chains;

(c) the first polypeptide chain comprises an IgG1 variant heavy chain constant region comprising SEQ ID NO;

47 mutated at one or more amino acid residues; and

(d) the second polypeptide chain comprises a light chain constant region of SEQ ID NO 48, and

(e) wherein the disease or disorder is selected from the group consisting of rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, septic arthritis, Lyme arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy, spondylitis ankylosans, systemic lupus erythematosus, Crohn'"'"'s disease, ulcerative colitis, inflammatory bowel disease, psoriasis, sarcoidosis, uveitis, atopic eczema, scleroderma, and amyotrophic lateral sclerosis.