Dual specific binding proteins directed against IL-13 and IL-17
First Claim
Patent Images
1. A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-(X2)n, whereinVD1 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 ofSEQ 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, orSEQ ID NO;
49 and SEQ ID NO;
51.
3 Assignments
0 Petitions
Accused Products
Abstract
Engineered multivalent and multispecific binding proteins that bind IL-13 and/or IL-17 are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.
-
Citations
16 Claims
-
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, orSEQ ID NO;
49 and SEQ ID NO;
51.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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.
- 1-29 or a G4S (SEQ ID NO;
-
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 3H, 14C, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, or 153Sm.
-
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).
-
Specification