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US 2014/0271457 A1Published application
Dual Specific Binding Proteins Directed Against TNF
AssigneeAbbVie Inc.
InventorsTariq Ghayur, Carrie Goodreau
Life of this patent
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Abstract
Engineered multivalent and multispecific binding proteins that bind TNFα and IL-13, TNFα and PGE2, or TNFα and NGF are provided, along with methods of making and uses in the prevention, diagnosis, and/or treatment of disease.
Claims36
1-34. (canceled)
A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-X2, wherein
- VD1 is a first variable domain;
- VD2 is a second variable domain;
- C is a constant domain;
- X1 is a linker;
- X2 is an Fc region that is either present or absent;
- 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
- (a) TNFα and IL-13, wherein
- (i) the variable domains that form a functional target binding site for TNFα comprise a sequence selected from the group consisting of SEQ ID NOs:
- 38-43 and 48-49, and
- (ii) the variable domains that form a functional target binding site for IL-13 comprise a sequence selected from the group consisting of SEQ ID NO:
- 32-37;
- (b) TNFα and PGE2, wherein
- (i) the variable domains that form a functional target binding site for TNFα comprise a sequence selected from the group consisting of SEQ ID NOs:
- 38-43 and 48-49, and
- (ii) the variable domains that form a functional target binding site for PGE2 comprise a sequence selected from the group consisting of SEQ ID NO:
- 50-55;
- or
- (c) TNFα and NGF, wherein
- (i) the variable domains that form a functional target binding site for TNFα comprise a sequence selected from the group consisting of SEQ ID NOs:
- 38-43 and 48-49, and
- (ii) the variable domains that form a functional target binding site for NGF comprise a sequence selected from the group consisting of SEQ ID NO:
- 56-57.
20 more elements
A binding protein comprising first and second polypeptide chains, each independently comprising VD1-(X1)n-VD2-C-X2, wherein
- VD1 is a first variable domain;
- VD2 is a second variable domain;
- C is a constant domain;
- X1 is a linker;
- X2 is an Fc region that is either present or absent;
- 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
- (a) TNFα and IL-13, wherein
- (i) the variable domains that form a functional target binding site for TNFα comprise:
- CDRs 1-3 from SEQ ID NO:
- 38 and CDRs 1-3 from SEQ ID NO:
- 39,
- CDRs 1-3 from SEQ ID NO:
- 40 and CDRs 1-3 from SEQ ID NO:
- 41,
- CDRs 1-3 from SEQ ID NO:
- 42 and CDRs 1-3 from SEQ ID NO:
- 43, or
- CDRs 1-3 from SEQ ID NO:
- 48 and CDRs 1-3 from SEQ ID NO:
- 49;
- and
- (ii) the variable domains that form a functional target binding site for IL-13 comprise
- CDRs 1-3 from SEQ ID NO:
- 32 and CDRs 1-3 from SEQ ID NO:
- 33;
- CDRs 1-3 from SEQ ID NO:
- 34 and CDRs 1-3 from SEQ ID NO:
- 35;
- or
- CDRs 1-3 from SEQ ID NO:
- 36 and CDRs 1-3 from SEQ ID NO:
- 37;
- (b) TNFα and PGE2, wherein
- (i) the variable domains that form a functional target binding site for TNFα comprise:
- CDRs 1-3 from SEQ ID NO:
- 38 and three CDRs from SEQ ID NO:
- 39,
- CDRs 1-3 from SEQ ID NO:
- 40 and three CDRs from SEQ ID NO:
- 41,
- CDRs 1-3 from SEQ ID NO:
- 42 and three CDRs from SEQ ID NO:
- 43, or
- CDRs 1-3 from SEQ ID NO:
- 48 and CDRs 1-3 from SEQ ID NO:
- 49;
- and
- (ii) the variable domains that form a functional target binding site for PGE2 comprise
- CDRs 1-3 from SEQ ID NO:
- 50 and CDRs 1-3 from SEQ ID NO:
- 51;
- CDRs 1-3 from SEQ ID NO:
- 52 and CDRs 1-3 from SEQ ID NO:
- 53;
- or
- CDRs 1-3 from SEQ ID NO:
- 54 and CDRs 1-3 from SEQ ID NO:
- 55;
- or
- (c) TNFα and NGF, wherein
- (i) the variable domains that form a functional target binding site for TNFα comprise;
- CDRs 1-3 from SEQ ID NO:
- 38 and CDRs 1-3 from SEQ ID NO:
- 39,
- CDRs 1-3 from SEQ ID NO:
- 40 and CDRs 1-3 from SEQ ID NO:
- 41,
- CDRs 1-3 from SEQ ID NO:
- 42 and CDRs 1-3 from SEQ ID NO:
- 43, or
- CDRs 1-3 from SEQ ID NO:
- 48 and CDRs 1-3 from SEQ ID NO:
- 49;
- and
- (ii) the variable domains that form a functional target binding site for NGF comprise
- CDRs 1-3 from SEQ ID NO:
- 56 and CDRs 1-3 from SEQ ID NO:
- 57.
76 more elements
A binding protein capable of binding
- (a) TNFα and IL-13, comprising a DVD-Ig VH and VL sequence pair from Table 2;
- (b) TNFα and PGE2, comprising a DVD-Ig VH and VL sequence pair from Table 3;
- or
- (c) TNFα and NGF, comprising a DVD-Ig VH and VL sequence pair from Table 4.
1 more element
Dependencies are inferred from the claim text.