IL-17 BINDING PROTEINS

• US 20100266531A1
• Filed: 03/05/2010
• Published: 10/21/2010
• Est. Priority Date: 03/05/2009
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: TARCSA, EDIT, PEREZ, JENNIFER M., KUTSKOVA, YULIYA, LEDDY, MARY R., ZHONG, SUJU, BRYANT, SHAUGHN H., HUGUNIN, MARGARET, MCRAE, BRADFORD L., WALLACE, CRAIG, MEMMOTT, JOHN E., CLABBERS, ANCA, MURTAZA, ANWAR, HSIEH, CHUNG-MING
• Granted Patent: US 8,835,610 B2
• Time in Patent Office: Days
• US Class Current: 424/85.200
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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 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 13/00 Drugs for disorders of the urinary system
• 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 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 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• 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 25/06 : 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 25/28 : 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 27/02 : Ophthalmic agents
• 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 3/10 : 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 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• 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 37/00 : Drugs for immunological or allergic disorders
• 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 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 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• 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: C07K 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/468 : Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/50 : characterized by immunoglobulin fragments
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/64 : comprising a combination of variable region and constant region components
• 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: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Proteins that bind IL-17 and/or IL-17F are described along with there use in composition and methods for treating, preventing, and diagnosing IL-17 related diseases and for detecting IL-17 in cells, tissues, samples, and compositions.

Claims

1. A binding protein comprising an antigen binding domain capable of binding human IL-17, said antigen binding domain comprises at least one CDR comprising an amino acid sequence selected from the group consisting of:

CDR-H1. X₁-X₂-X₃-X₄-X₅ (SEQ ID NO;

919), wherein;

X₁ is D or S;

X₂ is Y;

X₃ is E or G;

X₄ is I, M, V, or F;

X₅ is H;

CDR-H2. X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂-X₁₃-X₁₄-X₁₅-X₁₆-X₁₇ (SEQ ID NO;

920), wherein;

X₁ is V;

X₂ is T, I, or N;

X₃ is D, H, or W;

X₄ is P or is not present;

X₅ is E, G, or S;

X₆ is S, N, or D;

X₇ is G;

X₈ is G or T;

X₉ is T;

X₁₀ is L, A, T, or F;

X₁₁ is H or Y;

X₁₂ is N;

X₁₃ is P, Q, or S;

X₁₄ is K, A, or N;

X₁₅ is F or L;

X₁₆ is D, K, or R; and

X₁₇ is G, D, or S;

CDR-H3. X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂ (SEQ ID NO;

921), wherein;

X₁ is Y, F, or D;

X₂ is Y, L, S, or G;

X₃ is K, T, R, or Y;

X₄ is Y or W;

X₅ is E, D, or I;

X₆ is S, G, or Y;

X₇ is F, Y, or T;

X₈ is Y, F, or M;

X₉ is G, T, or is not present;

X₁₀ is M or is not present;

X₁₁ is D; and

X₁₂ is Y;

CDR-L1. X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂-X₁₃-X₁₄-X₁₅-X₁₆ (SEQ ID NO;

922), wherein;

X₁ is S, K, or R;

X₂ is A or S;

X₃ is S;

X₄ is S or Q;

X₅ is S or is not present;

X₆ is L or is not present;

X₇ is V or is not present;

X₈ is H or is not present;

X₉ is S or is not present;

X₁₀ is S, N, or is not present;

X₁₁ is S, V, or G;

X₁₂ is I, N, or S;

X₁₃ is S, N, T, or I;

X₁₄ is Y or D;

X₁₅ is M, V, L, or I; and

X₁₆ is C, A, H, Y, or G;

CDR-L2. X₁-X₂-X₃-X₄-X₅-X₆-X₇ (SEQ ID NO;

923), wherein;

X₁ is D, Y, K, A, or H;

X₂ is T, A, or V;

X₃ is S or F;

X₄ is K, N, or E;

X₅ is L or R;

X₆ is A, Y, or F; and

X₇ is S or T;

and

CDR-L3. X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉ (SEQ ID NO;

924), wherein;

X₁ is Q, S, or H;

X₂ is Q;

X₃ is R, D, S, or G;

X₄ is S, Y, or T;

X₅ is S, G, or H;

X₆ is Y, S, V, or A;

X₇ is P or is not present;

X₈ is W, Y, or L; and

X₉ is T.

2. The binding protein according to claim 1, wherein said at least one CDR comprises an amino acid sequence selected from the group consisting of:

residues 31-35 of SEQ ID NO;

26;

residues 50-66 of SEQ ID NO;

26;

residues 99-110 of SEQ ID NO;

26;

residues 24-33 of SEQ ID NO;

27;

residues 49-55 of SEQ ID NO;

27;

residues 88-96 of SEQ ID NO;

27;

residues 31-35 of SEQ ID NO;

28;

residues 50-66 of SEQ ID NO;

28;

residues 99-108 of SEQ ID NO;

28;

residues 24-34 of SEQ ID NO;

29;

residues 50-56 of SEQ ID NO;

29;

residues 89-97 of SEQ ID NO;

29;

residues 31-35 of SEQ ID NO;

30;

residues 50-66 of SEQ ID NO;

30;

residues 99-108 of SEQ ID NO;

30;

residues 24-34 of SEQ ID NO;

31;

residues 50-56 of SEQ ID NO;

31;

residues 89-97 of SEQ ID NO;

31;

residues 31-35 of SEQ ID NO;

32;

residues 50-65 of SEQ ID NO;

32;

residues 98-109 of SEQ ID NO;

32;

residues 24-39 of SEQ ID NO;

33;

residues 55-61 of SEQ ID NO;

33;

residues 94-101 of SEQ ID NO;

33;

residues 31-35 of SEQ ID NO;

34;

Residues 50-66 of SEQ ID NO;

34;

residues 99-110 of SEQ ID NO;

34;

residues 24-33 of SEQ ID NO;

35;

residues 49-55 of SEQ ID NO;

35;

residues 88-96 of SEQ ID NO;

35;

residues 31-35 of SEQ ID NO;

36;

residues 50-66 of SEQ ID NO;

36;

residues 99-108 of SEQ ID NO;

36;

residues 24-34 of SEQ ID NO;

37;

residues 50-56 of SEQ ID NO;

37;

residues 89-97 of SEQ ID NO;

37;

residues 31-35 of SEQ ID NO;

38;

residues 50-65 of SEQ ID NO;

38;

residues 98-107 of SEQ ID NO;

38;

residues 24-39 of SEQ ID NO;

39;

residues 55-61 of SEQ ID NO;

39; and

residues 94-102 of SEQ ID NO;

39.

3. The binding protein according to claim 2, wherein said binding protein comprises at least 3 CDRs.

4. The binding protein according to claim 3, wherein said at least 3 CDRs comprises a variable domain CDR set selected from the group consisting of:

5. The binding protein according to claim 4, comprising at least two variable domain CDR sets.

6. The binding protein according to claim 5, wherein said at least two variable domain CDR sets are selected from a group consisting of:

VH 7D7 CDR Set and VL 7D7 CDR Set;

VH 6C6 CDR Set and VL 6C6 CDR Set;

VH1D8 CDR Set and VL 1D8 CDR Set;

VH 8B12 CDR Set and VL 8B12 CDR Set;

VH 10F7 CDR Set and VL 10F7 CDR Set; and

VH 5C5 CDR Set and VL 5C5 CDR Set; and

VH 10G9 CDR Set and VL 10G9 Set.

7. The binding protein according to claim 6, further comprising a human acceptor framework.

8. The binding protein according to claim 7, wherein said human acceptor framework comprises an amino acid sequence selected from the group consisting of:

SEQ ID NO.;

7

SEQ ID NO.;

8

SEQ ID NO.;

9

SEQ ID NO.;

10

SEQ ID NO.;

11

SEQ ID NO.;

12

SEQ ID NO.;

13

SEQ ID NO.;

14

SEQ ID NO.;

15

SEQ ID NO.;

16

SEQ ID NO.;

17

SEQ ID NO.;

18

SEQ ID NO.;

19

SEQ ID NO.;

20

SEQ ID NO.;

21

SEQ ID NO.;

22

SEQ ID NO.;

23

SEQ ID NO.;

24 AND

SEQ ID NO.;

25.

9. The binding protein according to claim 7 or 8, wherein said human acceptor framework comprises at least one framework region amino acid substitution, wherein the amino acid sequence of the framework is at least 65% identical to the sequence of said human acceptor framework and comprises at least 70 amino acid residues identical to said human acceptor framework.

10. The binding protein according to claim 8, wherein said human acceptor framework comprises at least one framework region amino acid substitution at a key residue, said key residue selected from the group consisting of:

a residue adjacent to a CDR;

a glycosylation site residue;

a rare residue;

a residue capable of interacting with human IL-17;

a residue capable of interacting with a CDR;

a canonical residue;

a contact residue between heavy chain variable region and light chain variable region;

a residue within a Vernier zone; and

a residue in a region that overlaps between a Chothia-defined variable heavy chain CDR1 and a Kabat-defined first heavy chain framework.

11. The binding protein according to claim 10, wherein said key residue is selected from the group consisting of:

2H, 4H, 24H, 26H, 27H, 29H, 34H, 35H, 37H, 39H, 44H, 45H, 47H, 48H, 49H, 50H, 51H, 58H, 59H, 60H, 63H, 67H, 69H, 71H, 73H, 76H, 78H, 91H, 93H, 94H, 2L, 4L, 25L, 29L, 27bL, 33L, 34L, 36L, 38L, 43L, 44L, 46L, 47L, 48L, 49L, 55L, 58L, 62L, 64L, 71L, 87L, 89L, 90L, 91L, 94L, 95L.

12. The binding protein according to claim 11, wherein the binding protein is a consensus human variable domain.

13. The binding protein according to claim 1, wherein said binding protein comprises at least one variable domain having an amino acid sequence selected from the group consisting of:

SEQ ID NO;

60

SEQ ID NO;

61

SEQ ID NO;

62

SEQ ID NO;

63

SEQ ID NO;

64

SEQ ID NO;

65

SEQ ID NO;

66

SEQ ID NO;

67

SEQ ID NO;

68

SEQ ID NO;

69

SEQ ID NO;

70

SEQ ID NO;

71

SEQ ID NO;

72

SEQ ID NO;

73

SEQ ID NO;

74

SEQ ID NO;

75

SEQ ID NO;

76

SEQ ID NO;

931

SEQ ID NO;

932 AND

SEQ ID NO;

933.

14. The binding protein according to claim 13, wherein said binding protein comprises two variable domains, wherein said two variable domains have amino acid sequences selected from the group consisting of:

SEQ ID NO;

60 &

SEQ ID NO;

62,

SEQ ID NO;

60 &

SEQ ID NO;

63,

SEQ ID NO;

60 &

SEQ ID NO;

64,

SEQ ID NO;

60 &

SEQ ID NO;

65,

SEQ ID NO;

60 &

SEQ ID NO;

66

SEQ ID NO;

60 &

SEQ ID NO;

67,

SEQ ID NO;

60 &

SEQ ID NO;

68,

SEQ ID NO;

61 &

SEQ ID NO;

62,

SEQ ID NO;

61 &

SEQ ID NO;

63,

SEQ ID NO;

61 &

SEQ ID NO;

64,

SEQ ID NO;

61 &

SEQ ID NO;

65,

SEQ ID NO;

61 &

SEQ ID NO;

66,

SEQ ID NO;

61 &

SEQ ID NO;

67, AND

SEQ ID NO;

61 &

SEQ ID NO;

68.

15. The binding protein according to claim 11, wherein said binding protein comprises at least one variable domain having an amino acid sequence selected from the group consisting of:

SEQ ID NO;

60

SEQ ID NO;

61

SEQ ID NO;

62

SEQ ID NO;

63

SEQ ID NO;

64

SEQ ID NO;

65

SEQ ID NO;

66

SEQ ID NO;

67

SEQ ID NO;

68

SEQ ID NO;

69

SEQ ID NO;

70

SEQ ID NO.;

71

SEQ ID NO.;

72

SEQ ID NO.;

73

SEQ ID NO.;

74

SEQ ID NO.;

75

SEQ ID NO.;

76

SEQ ID NO;

931

SEQ ID NO;

932 AND

SEQ ID NO;

933.

18. The binding protein according to claim 1, wherein the binding protein is capable of modulating a biological function of IL-17.

19. The binding protein according to claim 1, wherein the binding protein is capable of neutralizing IL-17 activity.

20. The binding protein according to claim 14, wherein said binding protein has an on rate constant (K_on) to said target selected from the group consisting of:

at least about 10²M<sup>−

1</sup> s<sup>−

1</sup>;

at least about 10³M<sup>−

1</sup> s<sup>−

1</sup>;

at least about 10⁴M<sup>−

1</sup> s<sup>−

1</sup>;

at least about 10⁵M<sup>−

1</sup> s<sup>−

1</sup>; and

at least about 10⁶M<sup>−

1</sup> s<sup>−

1</sup>;

as measured by surface plasmon resonance.

21. The binding protein according to claim 14, wherein said binding protein has an off rate constant (K_off) to said target selected from the group consisting of:

at most about 10<sup>−

3</sup> s<sup>−

1</sup>;

at most about 10<sup>−

4</sup> s<sup>−

1</sup>;

at most about 10<sup>−

5</sup> s<sup>−

1</sup>; and

at most about 10<sup>−

6</sup> s<sup>−

1</sup>, as measured by surface plasmon resonance.

22. The binding protein according to claim 14, wherein said binding protein has a dissociation constant (K_D) to said target selected from the group consisting of:

at most about 10<sup>−

7</sup> M;

at most about 10<sup>−

8</sup> M;

at most about 10<sup>−

9</sup> M;

at most about 10<sup>−

10</sup> M;

at most about 10<sup>−

11</sup> M;

at most about 10<sup>−

12</sup> M; and

at most 10<sup>−

13</sup>M.

23. An IL-17 binding protein construct comprising a binding protein described in claim 1, said IL-17 binding protein construct further comprising a linker polypeptide or an immunoglobulin constant domain.

24. The IL-17 binding protein construct according to claim 23, wherein said binding protein is selected from the group consisting of:

an immunoglobulin molecule,

a monoclonal antibody,

a chimeric antibody,

a CDR-grafted antibody,

a humanized antibody,

a Fab,

a Fab′

,

a F(ab′

)2 ,

a Fv,

a disulfide linked Fv,

a scFv,

a single domain antibody,

a diabody,

a multispecific antibody,

a dual specific antibody,

a bispecific antibody, and

a DVD-Ig™

.

25. The IL-17 binding protein construct according to claim 23, wherein said binding protein comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

a human IgM constant domain,

a human IgG1 constant domain,

a human IgG2 constant domain,

a human IgG3 constant domain,

a human IgG4 constant domain,

a human IgE constant domain, and

a human IgA constant domain.

26. The IL-17 binding protein construct according to claim 23, comprising an immunoglobulin constant domain having an amino acid sequence selected from the group consisting of:

SEQ ID NO;

3

SEQ ID NO;

4

SEQ ID NO;

5

and

SEQ ID NO;

6.

27. An IL-17 binding protein conjugate comprising an IL-17 binding protein construct of claim 24, said IL-17 binding protein conjugate further comprising an agent selected from the group consisting of:

an immunoadhesion molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.

28. The IL-17 binding protein conjugate according to claim 27, 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.

32. The binding protein according to claim 1, wherein said binding protein is a crystallized binding protein.

33. The IL-17 binding protein construct according to claim 23, wherein said IL-17 binding protein construct is a crystallized IL-17 binding protein construct.

34. The IL-17 binding protein construct according to claim 33, wherein said crystallized IL-17 binding protein construct is a carrier-free pharmaceutical controlled release crystallized IL-17 binding protein construct.

37. An isolated nucleic acid encoding a binding protein amino acid sequence of claim 1.

38. An isolated nucleic acid encoding an IL-17 binding protein construct amino acid sequence of claim 23.

39. A vector comprising an isolated nucleic acid according to claim 37 or 38.

41. A host cell comprising a vector according to claim 39.

52. A method of producing a protein capable of binding IL-17, comprising culturing a host cell of claim 41 in culture medium under conditions sufficient to produce a binding protein capable of binding IL-17.

53. A protein produced according to the method of claim 52.

54. A composition for the release of a binding protein said composition comprising:

(a) a formulation, wherein said formulation comprises a crystallized binding protein, according to claim 33, and an ingredient; and

(b) at least one polymeric carrier.

55. The composition according to claim 54, 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 polysaccharides, blends and copolymers thereof.

56. The composition according to claim 54, wherein said ingredient is selected from the group consisting of albumin, sucrose, trehalose, lactitol, gelatin, hydroxypropyl-β

-cyclodextrin, methoxypolyethylene glycol and polyethylene glycol.

57. A method for treating a mammal comprising the step of administering to the mammal an effective amount of the composition according to claim 54.

58. A pharmaceutical composition comprising the binding protein of claim 1, and a pharmaceutically acceptable carrier.

63. A method for reducing human IL-17 activity comprising contacting human IL-17 with the binding protein of claim 1 such that human IL-17 activity is reduced.

64. A method for reducing human IL-17 activity in a human subject suffering from a disorder in which IL-17 activity is detrimental, comprising administering to the human subject the binding protein of claim 1 such that human IL-17 activity in the human subject is reduced.

65. A method for treating a subject for a disease or a disorder in which IL-17 activity is detrimental by administering to the subject the binding protein of claim 1 such that treatment is achieved.

66. The method of claim 65, 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 (e.g., from HTLV-1);

suppression of expression of protective type 1 immune responses, and suppression of expression of protective type 1 immune responses during vaccination.

67. The method of claim 64, 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 greata, seronegative arthropathy, arthropathy, Reiter'"'"'s disease, psoriatic arthropathy, ulcerative colitic arthropathy, enteropathic synovitis, chlamydia, yersinia and salmonella associated arthropathy, spondyloarthropathy, 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 vasculitis 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) Abetalipoproteinemia, 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, aortic and peripheral aneurysms, 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, chronic 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 arteriosclerotic 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, Hallervorden-Spatz disease, Hashimoto'"'"'s thyroiditis, hay fever, heart transplant rejection, hemachromatosis, hemodialysis, hemolytic uremic syndrome/thrombolytic thrombocytopenic purpura, hemorrhage, hepatitis (A), His bundle arrhythmias, HIV infection/HIV neuropathy, Hodgkin'"'"'s disease, hyperkinetic movement disorders, hypersensitivity 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, lymphedema, malaria, malignant 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, myelodysplastic 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, occlusive 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 atherosclerotic 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, Raynaud'"'"'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 arrhythmias, spinal ataxia, spinocerebellar degenerations, streptococcal myositis, structural lesions of the cerebellum, Subacute sclerosing panencephalitis, Syncope, syphilis of the cardiovascular system, systemic anaphylaxis, 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, viral encephalitis/aseptic meningitis, viral-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 greata, anaphylaxis, anti-phospholipid antibody syndrome, aplastic anemia, arteriosclerosis, atopic eczema, atopic dermatitis, autoimmune dermatitis, autoimmune disorder associated with streptococcus infection, autoimmune enteropathy, autoimmune hearing loss, 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 prolapse, drug induced immune hemolytic anemia, endocarditis, endometriosis, endophthalmitis, episcleritis, erythema multiforme, erythema multiforme major, gestational pemphigoid, Guillain-Barré

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, keratojunctivitis 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, ovarian cancer, 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, prostate and rectal cancer and hematopoietic malignancies (leukemia and lymphoma), 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, spondylitis 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, wound healing, yersinia and salmonella associated arthropathy.

68. A method of treating a patient suffering from a disorder in which IL-17 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 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;

adensosine agonists;

antithrombotic agents;

complement inhibitors;

adrenergic agents;

IRAK, NIK, IKK, p38, or MAP kinase inhibitors;

IL-1β

converting enzyme inhibitors;

TNF-α

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-β

.

69. The method according to claim 65, 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.

16-17. -17. (canceled)

29-31. -31. (canceled)

35-36. -36. (canceled)

40. (canceled)

42-51. -51. (canceled)

59-62. -62. (canceled)

70. A binding protein comprising an antigen binding domain capable of binding human IL-17, wherein said antigen binding domain comprises at least one CDR comprising an amino acid sequence selected from the group consisting of:

CDR-H1 selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅ (SEQ ID NO;

     925), wherein;

X₁ is N, A, D, or S;

X₂ is Y, F, or L;

X₃ is G, D, or A;

X₄ is M or I; and

X₅ is H, D, or S;

a CDR-H1 of a variable heavy chain region (VH) of Table 21;

a CDR-H1 of a VH of Table 23;

a CDR-H1 of a VH of Table 24; and

a CDR-H1 of a VH of Table 27;

CDR-H2, selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂-X₁₃-X₁₄-X₁₅-X₁₆-X₁₇ (SEQ ID NO;

926), wherein;

X₁ is V, W, or G;

X₂ is I, T, M, or F;

X₃ is S, N, T, or D;

X₄ is Y or P;

X₅ is D, N, or I;

X₆ is G, S, L, or E;

X₇ is S or G;

X₈ is N, T, or E;

X₉ is K, T, or A;

X₁₀ is Y, G, N, or V;

X₁₁ is Y or V;

X₁₂ is A;

X₁₃ is D, P, or Q;

X₁₄ is S, K, or N;

X₁₅ is V or F;

X₁₆ is K, R, or Q; and

X₁₇ is G;

a CDR-H2 of a VH of Table 21;

a CDR-H2 of a VH of Table 23;

a CDR-H2 of a VH of Table 24; and

a CDR-H2 of a VH of Table 27;

CDR-H3, selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂-X₁₃-X₁₄-X₁₅-X₁₆-X₁₇ (SEQ ID NO;

927), wherein;

X₁ is V, S, E, or I;

X₂ is G, S, P, or R;

X₃ is A, E, N, or P;

X₄ is S, D, or W;

X₅ is G, E, F, or L;

X₆ is D, G, or W;

X₇ is Y, I, N, or G;

X₈ is Y, T, G, or A;

X₉ is Y or I;

X₁₀ is S, G, or Y;

X₁₁ is Y, F, or T;

X₁₂ is G, T, or is not present;

X₁₃ is L, H, or is not present;

X₁₄ is H or is not present;

X₁₅ is F or is not present;

X₁₆ is D; and

X₁₇ is V, N, or Y;

a CDR-H3 of a VH of Table 21;

a CDR-H3 of a VH of Table 23;

a CDR-H3 of a VH of Table 24; and

a CDR-H1 of a VH of Table 27;

CDR-L1, selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁-X₁₂-X₁₃ (SEQ ID NO;

928),

wherein;

X₁ is S, R, or K;

X₂ is G or A;

X₃ is S or D;

X₄ is N, K, or Q;

X₅ is S or is not present;

X₆ is N or is not present;

X₇ is I, L, N, or D;

X₈ is G or I;

X₉ is S, N, G, or D;

X₁₀ is H, R, S, or D;

X₁₁ is S, Y, A, or D;

X₁₂ is V, A, L, or M; and

X₁₃ is N, C, or H;

a CDR-L1 of a variable light chain region (VL) of Table 21;

a CDR-L1 of a VL of Table 23;

a CDR-L1 of a VL of Table 25; and

a CDR-L1 of a VL of Table 27;

CDR-L2, selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅-X₆-X₇ (SEQ ID NO;

929), wherein;

X₁ is G, Q, Y, or E;

X₂ is I, D, or A;

X₃ is G, N, S, or T;

X₄ is Q, K, or T;

X₅ is R, S, or L;

X₆ is P, I, or V; and

X₇ is S or P;

a CDR-L2 of a VL of Table 21;

a CDR-L2 of a VL of Table 23;

a CDR-L2 of a VL of Table 25; and

a CDR-L2 of a VL of Table 27;

and

CDR-L3, selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅-X₆-X₇-X₈-X₉-X₁₀-X₁₁ (SEQ ID NO;

     930), wherein;

X₁ is A, Q, H, or L;

X₂ is T or Q;

X₃ is W, S, or H;

X₄ is D or T;

X₅ is D or S;

X₆ is S, T, L, or F;

X₇ is L, T, or P;

X₈ is G, H, or Y;

X₉ is G, S, or T;

X₁₀ is Y or is not present; and

X₁₁ is V or is not present;

a CDR-L3 of a VL of Table 21;

a CDR-L3 of a VL of Table 23;

a CDR-L3 of a VL of Table 25; and

a CDR-L3 of a VL of Table 27.

71. The binding protein according to claim 70, wherein said at least one CDR comprises an amino acid sequence selected from the group consisting of:

residues 31-35 of SEQ ID NO;

40;

residues 50-66 of SEQ ID NO.;

40;

residues 99-103 of SEQ ID NO.;

40;

residues 23-35 of SEQ ID NO;

41;

residues 51-57 of SEQ ID NO.;

41;

residues 90-110 of SEQ ID NO.;

41;

residues 31-35 of SEQ ID NO;

42;

residues 50-66 of SEQ ID NO.;

42;

residues 99-103 of SEQ ID NO.;

42;

residues 23-35 of SEQ ID NO;

43;

residues 51-57 of SEQ ID NO.;

43;

residues 90-110 of SEQ ID NO.;

43;

residues 31-35 of SEQ ID NO;

44;

residues 50-66 of SEQ ID NO.;

44;

residues 99-101 of SEQ ID NO.;

44;

residues 23-35 of SEQ ID NO;

45;

residues 51-57 of SEQ ID NO.;

45;

residues 90-110 of SEQ ID NO.;

45;

residues 31-35 of SEQ ID NO;

46;

residues 50-66 of SEQ ID NO.;

46;

residues 99-115 of SEQ ID NO.;

46;

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 31-35 of SEQ ID NO;

48;

residues 50-66 of SEQ ID NO.;

48;

residues 99-101 of SEQ ID NO.;

48;

residues 24-34 of SEQ ID NO;

49;

residues 50-56 of SEQ ID NO.;

49; and

residues 89-97 of SEQ ID NO.;

49;

an amino acid sequence for a CDR-H1, an amino acid sequence for a CDR-H2, and an amino acid sequence for a CDR-H3 of a VH in Table 21, Table 23, Table 24, or Table 27; and

an amino acid sequence for a CDR-L1, an amino acid sequence for a CDR-L2, and an amino acid sequence for a CDR-L3 of a VL in Table 21, Table 23, Table 25, or Table 27.

103. An isolated nucleic acid encoding a binding protein amino acid sequence of claim 70.

104. A vector comprising an isolated nucleic acid according to claim 103.

106. A host cell comprising a vector according to claim 104.

116. A method of producing a binding protein that binds human IL-17, comprising culturing the host cell of claim 106 in a culture medium under conditions sufficient to produce a binding protein that binds human IL-17.

117. A binding protein produced according to the method of claim 116.

118. The binding protein according to claim 70, wherein said binding protein exists as a crystal.

122. A composition for the release of a binding protein said composition comprising:

(a) a formulation, wherein said formulation comprises a crystallized binding protein, according to claim 118, and an ingredient; and

(b) at least one polymeric carrier.

125. A method for treating a mammal comprising the step of administering to the mammal an effective amount of the composition according to claim 122.

126. A pharmaceutical composition comprising the binding protein according to claim 70, and a pharmaceutically acceptable carrier.

129. A method for reducing human IL-17 activity comprising contacting human IL-17 with the binding protein according to claim 70 such that human IL-17 activity is reduced.

130. A method for reducing human IL-17 activity in a human subject suffering from a disorder in which IL-17 activity is detrimental, comprising administering to the human subject the binding protein according to claim 70 such that human IL-17 activity in the human subject is reduced.

131. A method for treating a subject for a disease or a disorder in which IL-17 activity is detrimental by administering to the subject the binding protein according to claim 70 such that treatment is achieved.

132. The method of claim 131, 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 greata, seronegative arthropathy, arthropathy, Reiter'"'"'s disease, psoriatic arthropathy, ulcerative colitic arthropathy, enteropathic synovitis, chlamydia, yersinia and salmonella associated arthropathy, spondyloarthropathy, 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 vasculitis 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) Abetalipoproteinemia, 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, aortic and peripheral aneurysms, 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, chronic 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 arteriosclerotic 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, Hallervorden-Spatz disease, Hashimoto'"'"'s thyroiditis, hay fever, heart transplant rejection, hemachromatosis, hemodialysis, hemolytic uremic syndrome/thrombolytic thrombocytopenic purpura, hemorrhage, hepatitis (A), His bundle arrhythmias, HIV infection/HIV neuropathy, Hodgkin'"'"'s disease, hyperkinetic movement disorders, hypersensitivity 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, lymphedema, malaria, malignant 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, myelodysplastic 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, occlusive 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 atherosclerotic 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, Raynaud'"'"'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 arrhythmias, spinal ataxia, spinocerebellar degenerations, streptococcal myositis, structural lesions of the cerebellum, Subacute sclerosing panencephalitis, Syncope, syphilis of the cardiovascular system, systemic anaphylaxis, 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, viral encephalitis/aseptic meningitis, viral-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 greata, anaphylaxis, anti-phospholipid antibody syndrome, aplastic anemia, arteriosclerosis, atopic eczema, atopic dermatitis, autoimmune dermatitis, autoimmune disorder associated with streptococcus infection, autoimmune enteropathy, autoimmune hearing loss, 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 prolapse, drug induced immune hemolytic anemia, endocarditis, endometriosis, endophthalmitis, episcleritis, erythema multiforme, erythema multiforme major, gestational pemphigoid, Guillain-Barré

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, keratojunctivitis 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, ovarian cancer, 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, prostate and rectal cancer and hematopoietic malignancies (leukemia and lymphoma), 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, spondylitis 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, wound healing, yersinia and salmonella associated arthropathy.

133. A method of treating a patient suffering from a disorder in which IL-17 is detrimental comprising the step of administering the binding protein according to claim 70 before, concurrent, or after the administration of a second agent, wherein the second agent is selected from the group consisting of an antibody, or fragment thereof, capable of binding human IL-12;

methotrexate;

an antibody, or fragment thereof, capable of binding human TNF;

corticosteroids, cyclosporin, rapamycin, FK506, and non-steroidal anti-inflammatory agents.

72-102. -102. (canceled)

105. (canceled)

107-115. -115. (canceled)

119-121. -121. (canceled)

123-124. -124. (canceled)

127-128. -128. (canceled)

134-138. -138. (canceled)

139. A binding protein comprising first and second polypeptide chains, wherein said first polypeptide chain comprises a first polypeptide of formula 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; and

X2 is an Fc region; and

wherein said second polypeptide chain comprises a second polypeptide of formula 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 0 or 1;

wherein the binding protein is capable of binding human IL-17 and TNF-α

;

wherein said first heavy chain variable domain VD1 of said first polypeptide comprises an amino acid sequence of a variable heavy region (VH) of a parent anti-TNF-α

antibody or antigen binding portion thereof and said first light chain variable domain VD1 of said second polypeptide comprises an amino acid sequence of a variable light region (VL) of a parent anti-TNF-α

antibody or antigen binding portion thereof;

wherein said second heavy chain variable domain VD2 of said first polypeptide comprises an amino acid sequence of a VH of a parent anti-IL-17 antibody or antigen binding portion thereof and said second light chain variable domain VD2 of said second polypeptide comprises an amino acid sequence of a VL of a parent anti-IL-17 antibody or antigen binding portion thereof;

wherein said VD1 and VD2 heavy chain variable domains comprise an amino acid sequence of any of SEQ ID NOs;

562, 572, 577, 592, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, and 882; and

wherein said VD1 and VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

567, 582, 587, 597, 602, 607, 612, 617, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 767, 777, 787, 797, 807, 817, 827, 847, 857, 867, and 877.

140. The binding protein according to claim 139, wherein X1 or X2 is an amino acid sequence selected from the group consisting of SEQ ID NOs:

887-918.

141. The binding protein according to claim 139, wherein the binding protein comprises two first polypeptide chains and two second polypeptide chains.

152. The binding protein according to claim 139 or 151, wherein said binding protein has an on rate constant (Kon) to IL-17 and/or TNF-α

selected from the group consisting of;

at least about 10²M<sup>−

1</sup> s<sup>−

1</sup>;

at least about 10³M<sup>−

1</sup> s<sup>−

1</sup>;

at least about 10⁴M<sup>−

1</sup> s<sup>−

1</sup>;

at least about 10⁵M<sup>−

1</sup> s<sup>−

1</sup>; and

at least about 10⁶M<sup>−

1</sup> s<sup>−

1</sup>, as measured by surface plasmon resonance.

153. The binding protein according to claim 139 or 151, wherein said binding protein has an off rate constant (Koff) to IL-17 and/or TNF-α

selected from the group consisting of;

at most about 10<sup>−

3</sup> s<sup>−

1</sup>;

at most about 10<sup>−

4</sup> s<sup>−

1</sup>;

at most about 10<sup>−

5</sup> s<sup>−

1</sup>; and

at most about 10<sup>−

6</sup> s<sup>−

1</sup>, as measured by surface plasmon resonance.

154. The binding protein according to claim 139 or 151, wherein said binding protein has a dissociation constant (K_D) to IL-17 and/or TNF-α

selected from the group consisting of;

at most about 10<sup>−

7</sup> M;

at most about 10<sup>−

8</sup>M;

at most about 10<sup>−

9</sup>M;

at most about 10<sup>−

10</sup> M;

at most about 10<sup>−

11</sup> M;

at most about 10<sup>−

12</sup>M; and

at most 10<sup>−

13</sup>M.

155. A binding protein conjugate comprising a binding protein according to claim 139 or claim 151, said binding protein conjugate further comprising an agent selected from the group consisting of:

an immunoadhesion molecule, an imaging agent, a therapeutic agent, and a cytotoxic agent.

159. The binding protein according to claim 139 or 151, wherein said binding protein is a crystallized binding protein.

163. An isolated nucleic acid encoding a binding protein amino acid sequence according to claim 139 or 151.

164. A vector comprising an isolated nucleic acid according to claim 163.

166. A host cell comprising a vector according to claim 164.

177. A method of producing a binding protein, comprising culturing a host cell described in claim 166 in culture medium under conditions sufficient to produce the binding protein.

178. The method according to claim 177, wherein at least 50% of the binding protein produced is a dual specific tetravalent binding protein.

181. A protein produced according to the method of claim 177.

182. A pharmaceutical composition comprising the binding protein of any one of claims 139, 151, and 181, and a pharmaceutically acceptable carrier.

185. A method for treating a subject for a disease or a disorder comprising administering to the subject the binding protein of any one of claims 139, 151, and 181 such that treatment is achieved.

186. The method of claim 185, wherein said disorder is selected from the group comprising 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 greata, seronegative arthropathy, arthropathy, Reiter'"'"'s disease, psoriatic arthropathy, ulcerative colitic arthropathy, enteropathic synovitis, chlamydia, yersinia and salmonella associated arthropathy, spondyloarthropathy, 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 vasculitis 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) Abetalipoproteinemia, 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, aortic and peripheral aneurysms, 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, chronic 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 arteriosclerotic 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, Hallervorden-Spatz disease, Hashimoto'"'"'s thyroiditis, hay fever, heart transplant rejection, hemachromatosis, hemodialysis, hemolytic uremic syndrome/thrombolytic thrombocytopenic purpura, hemorrhage, hepatitis (A), His bundle arrhythmias, HIV infection/HIV neuropathy, Hodgkin'"'"'s disease, hyperkinetic movement disorders, hypersensitivity 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, lymphedema, malaria, malignant 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, myelodysplastic 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, occlusive 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 atherosclerotic 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, Raynaud'"'"'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 arrhythmias, spinal ataxia, spinocerebellar degenerations, streptococcal myositis, structural lesions of the cerebellum, Subacute sclerosing panencephalitis, Syncope, syphilis of the cardiovascular system, systemic anaphylaxis, 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, viral encephalitis/aseptic meningitis, viral-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 greata, anaphylaxis, anti-phospholipid antibody syndrome, aplastic anemia, arteriosclerosis, atopic eczema, atopic dermatitis, autoimmune dermatitis, autoimmune disorder associated with streptococcus infection, autoimmune enteropathy, autoimmune hearing loss, 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 prolapse, drug induced immune hemolytic anemia, endocarditis, endometriosis, endophthalmitis, episcleritis, erythema multiforme, erythema multiforme major, gestational pemphigoid, Guillain-Barré

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, keratojunctivitis 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, ovarian cancer, 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, prostate and rectal cancer and hematopoietic malignancies (leukemia and lymphoma), 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, spondylitis 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, wound healing, yersinia and salmonella associated arthropathy.

142-150. -150. (canceled)

151. A binding protein capable of binding two antigens comprising four polypeptide chains, wherein a first and a third polypeptide chains comprise 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; and

X2 is an Fc region; and

wherein a second and a fourth polypeptide chains comprise 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 0 or 1;

wherein the binding protein is capable of binding human IL-17 and TNF-α

;

wherein the first heavy chain variable domain VD1 of the first and third polypeptide chains comprises an amino acid sequence of a variable heavy region (VH) of a parent anti-TNF-α

antibody or antigen binding portion thereof and the first light chain variable domain VD1 of the second and fourth polypeptide chains comprises an amino acid sequence of a variable light region (VL) of a parent anti-TNF-α

antibody or antigen binding portion thereof;

wherein the second heavy chain variable domain VD2 of the first and third polypeptide chains comprises an amino acid sequence of a VH of a parent anti-IL-17 antibody or antigen binding portion thereof and the second light chain variable domain VD2 of the second and fourth polypeptide chains comprises an amino acid sequence of a VL of a parent anti-IL-17 antibody or antigen binding portion thereof;

wherein the VD1 and VD2 heavy chain variable domains comprise an amino acid sequence of any of SEQ ID NOs;

562, 572, 577, 592, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, and 882; and

wherein the VD1 and VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

567, 582, 587, 597, 602, 607, 612, 617, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 767, 777, 787, 797, 807, 817, 827, 847, 857, 867, and 877.

156-162. -162. (canceled)

160-162. -162. (canceled)

165. (canceled)

167-176. -176. (canceled)

179-180. -180. (canceled)

183-184. -184. (canceled)

187. (canceled)

188. A method for generating a DVD-Ig binding protein capable of binding two antigens comprising the steps of:

a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding TNF-α

;

b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding human IL-17;

c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first heavy chain variable domain obtained from said first parent antibody or antigen binding portion thereof;

VD2 is a second heavy chain variable domain obtained from said second parent antibody or antigen binding portion thereof;

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 0 or 1; and

d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first light chain variable domain obtained from said first parent antibody or antigen binding portion thereof;

VD2 is a second light chain variable domain obtained from said second parent antibody or antigen binding thereof;

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 0 or 1; and

e) expressing said first, second, third and fourth polypeptide chains;

such that a DVD-Ig binding protein capable of binding TNF-α and

human IL-17 is generated,

wherein VD1 and VD2 heavy chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

of SEQ ID NOs;

562, 572, 577, 592, 627, 637, 647, 657, 667, 677, 687, 697, 707, 717, 727, 737, 747, 757, 762, 772, 782, 792, 802, 812, 822, 832, 842, 852, 862, 872, and 882; and

wherein the VD1 and VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs;

567, 582, 587, 597, 602, 607, 612, 617, 622, 632, 642, 652, 662, 672, 682, 692, 702, 712, 722, 732, 742, 752, 767, 777, 787, 797, 807, 817, 827, 847, 857, 867, and 877.

191. The method of claim 188, wherein said DVD-Ig binding protein exhibits at least one desired property exhibited by said first parent antibody or antigen binding portion thereof.

192. The method of claim 188, wherein said DVD-Ig binding protein exhibits at least one desired property exhibited by said second parent antibody or antigen binding portion thereof.

195. The method of claim 191, wherein said desired property is selected from one or more antibody parameters.

196. The method of claim 192, wherein said desired property is selected from one or more antibody parameters.

197. The method of claim 195, wherein said antibody parameters are selected from the group consisting of antigen specificity, affinity to antigen, potency, biological function, epitope recognition, stability, solubility, production efficiency, immunogenicity, pharmacokinetics, bioavailability, tissue cross reactivity, and orthologous antigen binding.

198. The method of claim 196, wherein said antibody parameters are selected from the group consisting of antigen specificity, affinity to antigen, potency, biological function, epitope recognition, stability, solubility, production efficiency, immunogenicity, pharmacokinetics, bioavailability, tissue cross reactivity, and orthologous antigen binding.

199. The method of claim 188, wherein said first parent antibody or antigen binding portion thereof, binds said first antigen with a different affinity than the affinity with which said second parent antibody or antigen binding portion thereof, binds said second antigen.

200. The method of claim 188, wherein said first parent antibody or antigen binding portion thereof, binds said first antigen with a different potency than the potency with which said second parent antibody or antigen binding portion thereof, binds said second antigen.

189-190. -190. (canceled)

193-194. -194. (canceled)

201. (canceled)