Interleukin-13 binding proteins

• US 7,915,388 B2
• Filed: 09/07/2007
• Issued: 03/29/2011
• Est. Priority Date: 09/08/2006
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbott Laboratories
• Inventors: Melim, Terry L., Argiriadi, Maria A., Kumar, Shankar, Belk, Jonathan P., Wu, Chengbin, Hinton, Paul R., Chen, Yan, Cuff, Carolyn A., Ying, Hua, Dixon, Richard W.
• Primary Examiner(s): Yu; Misook
• Assistant Examiner(s): Natarajan; Meera
• Application Number:
  US11/899,819
• Publication Number:
  US 20080171014A1
• Time in Patent Office: 1,299 Days
• Field of Search: None
• US Class Current: 530/387.9
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 17/06 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 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/02 : for peripheral neuropathies
• 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 25/24 : 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• 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 31/12 : Antivirals
• 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 37/00 : Drugs for immunological or allergic disorders
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• 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 9/10 : 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 14/47 : from mammals
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• 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

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Claims

1. A binding protein comprising an antigen binding domain, said binding protein capable of binding IL-13, said antigen binding domain comprising six CDRs:

CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein;

CDR-H1 is selected from the group consisting of;

X₁-X₂-X₃-X₄-X₅-X₆-X₇ (SEQ ID NO;

     64), wherein;

X₁ is T, D, G, or S;

X₂ is S;

X₃ is D;

X₄ is M, S, Y, L, or H;

X₅ is G, W, Y, A, S, or N;

X₆ is V, I, or M; and

X₇ is D, H, S, Y, N, or G;

residues 31-35 of SEQ ID NO;

32;

residues 31-35 of SEQ ID NO;

34;

residues 31-35 of SEQ ID NO;

36;

residues 31-35 of SEQ ID NO;

38;

residues 31-35 of SEQ ID NO;

39;

residues 31-35 of SEQ ID NO;

41;

residues 31-35 of SEQ ID NO;

42;

residues 31-35 of SEQ ID NO;

44;

residues 31-35 of SEQ ID NO;

52;

residues 31-35 of SEQ ID NO;

54;

residues 31-35 of SEQ ID NO;

56;

residues 31-35 of SEQ ID NO;

58;

residues 31-35 of SEQ ID NO;

60; and

residues 31-35 of SEQ ID NO;

62;

CDR-H2 is 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;

     65), wherein;

X₁ is M, E, H, R, S, G, or L;

X₂ is I or not present;

X₃ is H, Y, A, D, S, or W;

X₄ is P, S, W, or G;

X₅ is S, G, E, or D;

X₆ is D, G, S, E, or N;

X₇ is S, Y or G;

X₈ is E, N, Y, V, or R;

X₉ is T, I, or K;

X₁₀ is R, Y, I, D, or A;

X₁₁ is L, Y, D, or F;

X₁₂ is N, P, S, or D;

X₁₃ is Q, E, D, P, or S;

X₁₄ is K, M, S, T, A, or V;

X₁₅ is F, L, V, or M;

X₁₆ is K, R, or Q; and

X₁₇ is D, G, or S;

residues 50-65 of SEQ ID NO;

44;

residues 52-67 of SEQ ID NO;

46;

residues 52-67 of SEQ ID NO;

48;

residues 52-67 of SEQ ID NO;

50;

residues 50-65 of SEQ ID NO;

54;

residues 50-65 of SEQ ID NO;

56;

residues 50-65 of SEQ ID NO;

58;

residues 50-65 of SEQ ID NO;

60; and

residues 50-65 of SEQ ID NO;

62;

CDR-H3 is selected from the group consisting of;

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

     66), wherein;

X₁ is W, T, G, Y, D, or I;

X₂ is R, A, S, G, or V;

X₃ is T, F, Y, or S;

X₄ is S, T, or Y;

X₅ is Y, F, or G;

X₆ is F, or Y;

X₇ is S, Y, I, or F;

X₈ is D, L, Y, or P;

X₉ is Y;

X₁₀ is G;

X₁₁ is Y, A, P, or E;

X₁₂ is F, M, S, L, or I;

X₁₃ is D, V, N, or K; and

X₁₄ is Y, or F;

residues 99-105 of SEQ ID NO;

32;

residues 99-105 of SEQ ID NO;

34;

residues 99-109 of SEQ ID NO;

36;

residues 99-109 of SEQ ID NO;

38;

residues 99-100 of SEQ ID NO;

42;

residues 98-106 of SEQ ID NO;

44;

residues 100-112 of SEQ ID NO;

46;

residues 100-112 of SEQ ID NO;

48;

residues 100-112 of SEQ ID NO;

50;

residues 99-107 of SEQ ID NO;

52;

residues 98-107 of SEQ ID NO;

54;

residues 98-107 of SEQ ID NO;

56;

residues 98-107 of SEQ ID NO;

58;

residues 98-107 of SEQ ID NO;

60; and

residues 98-107 of SEQ ID NO;

62;

CDR-L1 is 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;

     67), wherein;

X₁ is K, or R;

X₂ is S, or A;

X₃ is S or T;

X₄ is Q, K, or I;

X₅ is N, S, T, G, or E;

X₆ is L, T, or S;

X₇ is L, Q, or V;

X₈ is Y, N, H, D, or T;

X₉ is S, I, or T;

X₁₀ is S, D, N, H, or Y;

X₁₁ is N, or G;

X₁₂ is Q;

X₁₃ is K, F, N, E, or S;

X₁₄ is N, T, or S;

X₁₅ is Y, or F;

X₁₆ is L, A, or M; and

X₁₇ is A, D, E, H, or N;

residues 24-39 of SEQ ID NO;

33;

residues 24-39 of SEQ ID NO;

35;

residues 24-39 of SEQ ID NO;

37;

residues 24-39 of SEQ ID NO;

40;

residues 24-39 of SEQ ID NO;

43;

residues 24-34 of SEQ ID NO;

47;

residues 24-34 of SEQ ID NO;

49;

residues 24-34 of SEQ ID NO;

51;

residues 23-36 of SEQ ID NO;

53;

residues 24-38 of SEQ ID NO;

55;

residues 24-38 of SEQ ID NO;

57;

residues 24-38 of SEQ ID NO;

59;

residues 24-38 of SEQ ID NO;

61; and

residues 24-38 of SEQ ID NO;

63;

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

     68), wherein;

X₁ is L, S, K, T, W, or Y;

X₂ is V, T, or A;

X₃ is S, or N;

X₄ is N, K, T, M, or R;

X₅ is R, K, or L;

X₆ is F, D, E, H, P, or A; and

X₇ is S, R, or P;

and

CDR-L3 is selected from the group consisting of;

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

     69), wherein;

X₁ is F, W, Q or A;

X₂ is Q or L;

X₃ is H, G, Y, W, or N;

X₄ is N, S, T, L, or Y;

X₅ is Y, T, S, E, or H;

X₆ is L, V, F, Y, N, G, P, or D;

X₇ is P, or, H;

X₈ is L, F, Y, W, or R; and

X₉ is T, or V; and

residues 94-102 of SEQ ID NO;

40.

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

3. The binding protein according to claim 1, wherein at least 3 CDRs are selected from a variable domain CDR set selected from the group consisting of:

4. The binding protein according to claim 3, comprising at least two variable domain CDR sets.

5. The binding protein according to claim 4, wherein said at least two variable domain CDR sets are selected from a group consisting of:

VH 25C8 CDR Set &

VL 25C8 CDR Set;

VH 9C11 CDR Set &

VL 9C11 CDR Set;

VH 21D9 CDR Set &

VL 21D9 CDR Set;

VH 22D10 CDR Set &

VL 22D10 CDR Set;

VH 5F1 CDR Set &

VL 5F1 CDR Set;

VH 5G1 CDR Set &

VL 5G1 CDR Set;

VH 3H7 CDR Set &

VL 3H7 CDR Set;

VH 14B2 CDR Set &

VL 14B2 CDR Set;

VH 13C5 CDR Set &

VL 13C5 CDR Set;

VH 29G5 CDR Set &

VL 29G5 CDR Set;

VH 33C3 CDR Set &

VL 33C3 CDR Set;

VH 4A8 CDR Set &

VL 4A8 CDR Set;

VH 1B6 CDR Set &

VL 1B6 CDR Set;

VH 3E5CDR Set &

VL 3E5 CDR Set;

VH 6C8 CDR Set &

VL 6C8 CDR Set;

VH 5D3 CDR Set &

VL 5D3 CDR Set; and

VH 8B6 CDR Set &

VL 8B6 CDR Set.

6. The binding protein according to claim 5, further comprising a human acceptor framework.

7. The binding protein according to claim 6, wherein said human acceptor framework comprises an amino acid sequence selected from the group consisting of:

8. The binding protein according to claim 6, 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.

9. The binding protein according to claim 7, 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-13;

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.

10. The binding protein according to claim 9, wherein the key residue is selected from the group consisting of 2L, 15L, 22L, 41L, 42L, 44L, 49L, 50L, 51L, 62L, 71L, 73L, 10H, 44H, 46H, 48H, 67H, 68H, 70H, 72H, 74H, 76H, 83H, 84H, 86H, 87H, and 97H.

11. The binding protein according to claim 10, wherein the binding protein is a consensus human variable domain.

12. 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:

13. The binding protein according to claim 12 wherein said binding protein comprises two variable domains, wherein said two variable domains have amino acid sequences selected from the group consisting of:

14. The binding protein according to claim 10, wherein said binding protein comprises at least one variable domain having an amino acid sequence selected from the group consisting of:

SEQ ID NO.;

70 SEQ ID NO.;

78 SEQ ID NO.;

92

SEQ ID NO.;

71 SEQ ID NO.;

79 SEQ ID NO.;

93

SEQ ID NO.;

72 SEQ ID NO.;

80 and

SEQ ID NO.;

73 SEQ ID NO.;

81 SEQ ID NO.;

94.

SEQ ID NO.;

74 SEQ ID NO.;

82

SEQ ID NO.;

75 SEQ ID NO.;

83

SEQ ID NO.;

76 SEQ ID NO.;

84

SEQ ID NO.;

77 SEQ ID NO.;

85.

15. The binding protein according to claim 1 or 13, wherein the binding protein is capable of modulating a biological function of IL-13.

16. The binding protein according to claim 1 or 13, wherein the binding protein is capable of neutralizing IL-13.

17. The binding protein according to claim 1 or 13, 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.

18. The binding protein according to claim 1 or 13, 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.

19. The binding protein according to claim 1 or 13, 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.

20. An antibody construct comprising a binding protein described in claim 1, said antibody construct further comprising a linker polypeptide or an immunoglobulin constant domain.

21. The antibody construct according to claim 20, wherein the antibody construct is selected from the group consisting of:

an immunoglobulin molecule, a disulfide linked Fv,

a monoclonal antibody, a scFv,

a chimeric antibody, a single domain antibody,

a CDR-grafted antibody, a diabody,

a humanized antibody, a multispecific antibody,

a Fab, a dual specific antibody, and

a Fab′

, a bispecific antibody.

a F(ab′

)2,

a Fv.

22. The antibody construct according to claim 20, wherein the antibody construct comprises a heavy chain immunoglobulin constant domain selected from the group consisting of:

a human IgM constant domain, a human IgG4 constant domain,

a human IgG1 constant domain, a human IgE constant domain,

a human IgG2 constant domain, and

a human IgG3 constant domain, a human IgA constant domain.

23. The antibody construct according to claim 20, wherein the antibody construct comprises an immunoglobulin constant domain having an amino acid sequence selected from the group consisting of:

SEQ ID NO.;

2

SEQ ID NO.;

3

SEQ ID NO.;

4

and

SEQ ID NO.;

5.

24. An antibody conjugate comprising an antibody construct of claim 21, said antibody conjugate further comprising an agent selected from the group consisting of:

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

25. The antibody conjugate according to claim 24, 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.

26. The antibody conjugate according to claim 24, wherein said imaging agent is a radiolabel selected from the group consisting of:

³H, ¹⁴C, ³⁵S, ⁹⁰Y, ⁹⁹Tc, ¹¹¹In, ¹²⁵I, ¹³¹I, ¹⁷⁷Lu, ¹⁶⁶Ho, and ¹⁵³Sm.

27. The antibody conjugate according to claim 24, wherein said agent is a therapeutic or cytotoxic agent selected from the group consisting of;

an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, and an apoptotic agent.

28. The antibody construct according to claim 21, wherein the antibody construct possesses a human glycosylation pattern.

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

30. The antibody construct according to claim 20, wherein said antibody construct is a crystallized antibody construct.

31. The antibody construct according to claim 30, wherein said crystallized antibody construct is a carrier-free pharmaceutical controlled release crystallized antibody construct.

32. The antibody construct according to claim 31, wherein said antibody construct has a greater half life in vivo than the soluble counterpart of said antibody construct.

33. The antibody construct according to claim 31, wherein said antibody construct retains biological activity.

34. A composition for the release of an antibody construct said composition comprising:

(a) a formulation, wherein said formulation comprises a crystallized antibody construct according to claim 30, and an ingredient; and

(b) at least one polymeric carrier.

35. The composition according to claim 34, 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.

36. The composition according to claim 34, wherein said ingredient is selected from the group consisting of albumin, sucrose, trehalose, lactitol, gelatin, hydroxypropyl-β

-cyclodextrin, methoxypolyethylene glycol and polyethylene glycol.

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

38. The pharmaceutical composition of claim 37, wherein said pharmaceutically acceptable carrier functions as adjuvant useful to increase the absorption, or dispersion of said binding protein.

39. The pharmaceutical composition of claim 38, wherein said adjuvant is hyaluronidase.

40. The pharmaceutical composition of claim 37, further comprising at least one additional therapeutic agent for treating a disorder in which IL-13 activity is detrimental.

41. The pharmaceutical composition of claim 37 comprising an additional agent, wherein said additional agent is selected from the group consisting of:

a therapeutic agent, an imaging agent, a cytotoxic agent, an angiogenesis inhibitor, a kinase inhibitor, a co-stimulation molecule blocker, an adhesion molecule blocker, an anti-cytokine antibody or functional fragment thereof;

methotrexate, a cyclosporin, a rapamycin, an FK506, a detectable label or reporter, a TNF antagonist, an anti-rheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anesthetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteroid, an anabolic steroid, an erythropoietin, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, a radiopharmaceutical, an antidepressant, an antipsychotic, a stimulant, an asthma medication, a beta agonist, an inhaled steroid, an oral steroid, an epinephrine or analog, a cytokine, and a cytokine antagonist.