Dual specific binding proteins directed against IL-13 and IL-17

1. A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first antibody variable domain;

VD2 is a second antibody variable domain;

C is an antibody constant domain;

X1 is a linker;

X2 is an antibody Fc region; and

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, and wherein the binding protein binds IL-13 and IL-17, wherein

(a) the variable domains that form a functional target binding site for IL-13 comprise the amino acid sequences of SEQ ID NO: 32 and SEQ ID NO:33, and

(b) the variable domains that form a functional target binding site for IL-17 comprise the amino acid sequences of

SEQ ID NO: 36 and SEQ ID NO: 37,

SEQ ID NO: 38 and SEQ ID NO: 39,

SEQ ID NO: 40 and SEQ ID NO: 41,

SEQ ID NO: 42 and SEQ ID NO: 52,

SEQ ID NO: 42 and SEQ ID NO: 53,

SEQ ID NO: 43 and SEQ ID NO: 50,

SEQ ID NO: 44 and SEQ ID NO: 51,

SEQ ID NO: 45 and SEQ ID NO: 54,

SEQ ID NO: 46 and SEQ ID NO: 51,

SEQ ID NO: 47 and SEQ ID NO: 54,

SEQ ID NO: 48 and SEQ ID NO: 51, or

SEQ ID NO: 49 and SEQ ID NO: 51.

2. The binding protein according to claim 1 , wherein the first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first antibody heavy chain variable domain;

VD2 is a second antibody heavy chain variable domain;

C is an antibody heavy chain constant domain;

X1 is a linker;

X2 is an antibody Fc region; and

n is 0 or 1,

wherein the second polypeptide chain comprises a second VD1-(X1)n-VD2-C, wherein

VD1 is a first antibody light chain variable domain;

VD2 is a second antibody light chain variable domain;

C is an antibody light chain constant domain;

X1 is a linker;

n is 1 for (X1)n; and

n is 0 for (X2)n,

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

3. The binding protein according to claim 1 , wherein X1 comprises the amino acid sequence of any one of SEQ ID NOs: 1-29 or a G4S (SEQ ID NO: 29) repeating sequence.

4. The binding protein according to claim 1 , wherein the Fc region is a variant sequence Fc region.

5. The binding protein according to claim 1 , wherein the Fc region is an Fc region from IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, or IgD.

6. The binding protein according to claim 1 , comprising two first polypeptide chains and two second polypeptide chains.

7. A pharmaceutical composition comprising the binding protein according to claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7 , further comprising at least one additional therapeutic agent.

9. A kit for assaying a test sample for the presence, amount, or concentration of IL13 and/or IL17 in the sample, said kit comprising:

(a) instructions for assaying the test sample for IL13 and/or IL17; and

(b) at least one binding protein according to claim 1 .

10. A binding protein conjugate comprising the binding protein according to claim 1 and an immunoadhesion molecule, an imaging agent, a therapeutic agent, or a cytotoxic agent.

11. The binding protein conjugate according to claim 10 , wherein the imaging agent is a radiolabel, an enzyme, a fluorescent label, a luminescent label, a bioluminescent label, a magnetic label, or biotin.

12. The binding protein conjugate according to claim 11 , wherein said radiolabel is 3 H, 14 C, 35 S, 90 Y, 99 Tc, 111 In, 125 I, 131 I, 177 Lu, 166 Ho, or 153 Sm.

13. The binding protein conjugate according to claim 10 , wherein said therapeutic or cytotoxic agent is an anti-metabolite, an alkylating agent, an antibiotic, a growth factor, a cytokine, an anti-angiogenic agent, an anti-mitotic agent, an anthracycline, toxin, or an apoptotic agent.

14. The binding protein according to claim 1 , wherein the binding protein is a crystallized binding protein.

15. A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, wherein

VD1 is a first antibody variable domain;

VD2 is a second antibody variable domain;

C is an antibody constant domain;

X1 is a linker;

X2 is an antibody Fc region; and

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, and wherein the binding protein binds IL-13 and IL-17, wherein

(a) the variable domains that form a functional target binding site for IL-13 comprise the amino acid sequences of SEQ ID NO: 32 and SEQ ID NO:33, and

(b) the variable domains that form a functional target binding site for IL-17 comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, and 54.

16. An IL-13 and IL-17 binding protein, wherein the binding protein comprises the amino acid sequences of any one of:

(a) DVD2166H (comprising SEQ ID NOs: 32 and 36) and DVD2166L (comprising SEQ ID NOs: 33 and 37);

(b) DVD2167H (comprising SEQ ID NOs: 36 and 32) and DVD2167L (comprising SEQ ID NOs: 37 and 33);

(c) DVD2168H (comprising SEQ ID NOs: 32 and 36) and DVD2168L (comprising SEQ ID NOs: 33 and 37);

(d) DVD2169H (comprising SEQ ID NOs: 36 and 32) and DVD2169L (comprising SEQ ID NOs: 37 and 33);

(e) DVD2170H (comprising SEQ ID NOs: 32 and 36) and DVD2170L (comprising SEQ ID NOs: 33 and 37);

(f) DVD2171H (comprising SEQ ID NOs: 36 and 32) and DVD2171L (comprising SEQ ID NOs: 37 and 33);

(g) DVD2172H (comprising SEQ ID NOs: 32 and 38) and DVD2172L (comprising SEQ ID NOs: 33 and 39);

(h) DVD2173H (comprising SEQ ID NOs: 38 and 32) and DVD2173L (comprising SEQ ID NOs: 39 and 33);

(i) DVD2174H (comprising SEQ ID NOs: 32 and 38) and DVD2174L (comprising SEQ ID NOs: 33 and 39);

(j) DVD2175H (comprising SEQ ID NOs: 38 and 32) and DVD2175L (comprising SEQ ID NOs: 39 and 33);

(k) DVD2176H (comprising SEQ ID NOs: 32 and 38) and DVD2176L (comprising SEQ ID NOs: 33 and 39);

(l) DVD2177H (comprising SEQ ID NOs: 38 and 32) and DVD2177L (comprising SEQ ID NOs: 39 and 33);

(m) DVD2178H (comprising SEQ ID NOs: 32 and 40) and DVD2178L (comprising SEQ ID NOs: 33 and 41);

(n) DVD2179H (comprising SEQ ID NOs: 40 and 32) and DVD2179L (comprising SEQ ID NOs: 41 and 33);

(o) DVD2180H (comprising SEQ ID NOs: 32 and 40) and DVD2180L (comprising SEQ ID NOs: 33 and 41);

(p) DVD2181H (comprising SEQ ID NOs: 40 and 32) and DVD2181L (comprising SEQ ID NOs: 41 and 33);

(q) DVD2182H (comprising SEQ ID NOs: 32 and 40) and DVD2182L (comprising SEQ ID NOs: 33 and 41); and

(r) DVD2183H (comprising SEQ ID NOs: 40 and 32) and DVD2183L (comprising SEQ ID NOs: 41 and 33).