DUAL VARIABLE DOMAIN IMMUNOGLOBULINS AND USES THEREOF

1 - 90 . (canceled)

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

VD1 is a first variable domain;

VD2 is a second variable domain;

C is constant domain;

X1 is a linker;

X2 is an Fc region;

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, wherein the binding protein is capable of binding IL-1β, and wherein the variable domains that form a functional target binding site for IL-1β comprise CDRs 1-3 from SEQ ID NO: 30 and CDRs 1-3 from SEQ ID NO: 31.

92 . The binding protein of claim 91 , wherein the variable domains that form functional binding sites for IL-1β comprise SEQ ID NO: 30 and SEQ ID NO: 31.

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

VD1 is a first variable domain;

VD2 is a second variable domain;

C is constant domain;

X1 is a linker;

X2 is an Fc region;

n is 0 or 1;

wherein the VD1 domains on the first and second polypeptide chains form a first functional target binding site and the VD2 domains on the first and second polypeptide chains form a second functional target binding site, and wherein the binding protein is capable of binding IL-1β and IL-1α, wherein the variable domains that form a functional target binding site for IL-1β comprise CDRs 1-3 from SEQ ID NO: 30 and CDRs 1-3 from SEQ ID NO: 31.

94 . The binding protein of claim 93 , wherein the variable domains that form a functional target binding site for IL-1β comprise SEQ ID NO: 30 and SEQ ID NO: 31.

95 . The binding protein of claim 91 , comprising first and second polypeptide chains, wherein

(a) the first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein

VD 1 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;

X2 is an Fc region;

n is 0 or 1; and

(b) the second polypeptide chain comprises a second 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;

n is 0 or 1 for (X1)n; and

n is 0 for (X2)n.

96 . The binding protein of claim 91 , comprising two first polypeptide chains and two second polypeptide chains and four functional target binding sites.

97 . The binding protein of claim 91 , wherein X1 comprises at least one of SEQ ID NO: 1-29.

98 . An isolated nucleic acid encoding the binding protein amino acid sequence of claim 91 .

99 . A vector comprising the isolated nucleic acid of claim 98 .

100 . A host cell comprising the vector of claim 99 , wherein the host cell is selected from a group consisting of a prokaryotic cell, Escherichia coli , a eukaryotic cell, an animal cell, a plant cell, a fungal cell, a yeast cell, an Sf9 cell, a mammalian cell, an avian cell, an insect cell, a CHO cell, and a COS cell.

101 . A method of producing a binding protein, comprising culturing the host cell of claim 100 in culture medium under conditions sufficient to produce the binding protein.

102 . A method of treating a subject for a disease or a disorder, comprising administering the binding protein of claim 91 to the subject.

103 . A method of determining the presence, amount, or concentration of IL-1β and/or IL-1α in a test sample by an immunoassay,

wherein the immunoassay comprises contacting the test sample with at least one binding protein and at least one detectable label, and

wherein the at least one binding protein comprises the binding protein of claim 93 .

104 . The binding protein of claim 93 , comprising first and second polypeptide chains, wherein

(c) the first polypeptide chain comprises a first VD1-(X1)n-VD2-C-(X2)n, wherein

VD 1 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;

X2 is an Fc region;

n is 0 or 1; and

(d) the second polypeptide chain comprises a second 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;

n is 0 or 1 for (X1)n; and

n is 0 for (X2)n.

105 . The binding protein of claim 93 , comprising two first polypeptide chains and two second polypeptide chains and four functional target binding sites.

106 . The binding protein of claim 93 , wherein X1 comprises at least one of SEQ ID NO: 1-29.

107 . An isolated nucleic acid encoding the binding protein amino acid sequence of claim 93 .

108 . A vector comprising the isolated nucleic acid of claim 107 .

109 . A host cell comprising the vector of claim 108 , wherein the host cell is selected from a group consisting of a prokaryotic cell, Escherichia coli , a eukaryotic cell, an animal cell, a plant cell, a fungal cell, a yeast cell, an Sf9 cell, a mammalian cell, an avian cell, an insect cell, a CHO cell, and a COS cell.

110 . A method of producing a binding protein, comprising culturing the host cell of claim 109 in culture medium under conditions sufficient to produce the binding protein.

111 . A pharmaceutical composition comprising the binding protein of claim 93 and a pharmaceutically acceptable carrier.

112 . A method of treating a subject for a disease or a disorder, comprising administering the binding protein of claim 93 to the subject.