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US 2012/0258108 A1Published application
Dual Variable Domain Immunoglobulins and Uses Thereof
AssigneeAbbott Laboratories
InventorsTariq Ghayur, Junjian Liu, Jijie Gu, Maria C. Harris
Life of this patent
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Abstract
Engineered multivalent and multispecific binding proteins, methods of making, and their uses in the prevention, diagnosis, and/or treatment of disease are provided.
Claims71
A binding protein that binds a pair of antigens, comprising a polypeptide chain, wherein said polypeptide chain comprises VD1-(X1)n-VD2-C—(X2)n, wherein;
- VD1 is a tint heavy chain variable domain;
- VD2 is a second heavy chain variable domain;
- C is a heavy chain constant domain;
- X1 is a linker with the proviso that it is not CH1;
- X2 is an Fc region;
- (X1)n is (X1)0 or (X1)1;
- and
- (X2)n is (X2)0 or (X2)1
- wherein the pair of antigens is TNF and PGE2 or VEGF and DLL4, and
- wherein the VD1 and VD2 independently comprise three CDRs from SEQ ID NO:
- 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, or 302.
8 more elements
A binding protein that hinds a pair of antigens, comprising a polypeptide chain, wherein said polypeptide chain comprises 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 with the proviso that it is not CL;
- X2 does not comprise an Fc region;
- (X1)n is (X1)0 or (X1)1;
- and
- (X2)n is (X2)0 or (X2)1
- wherein the pair of antigens is TNF and PGE2 or VEGF and DLL4, and
- wherein the VD1 and VD2 independently comprise three CDRs from SEQ ID NO:
- 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, or 303.
8 more elements
A binding protein that binds a pair of antigens, comprising first and second polypeptide chains, wherein said first polypeptide chain comprises a first VD1-(X1)n-VD2-C—(X2)n, wherein
- VD1 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 first linker;
- X2 is an Fc region;
- (X1)n is (X1)0 or (X1)1;
- and
- (X2)n is (X2)0 or (X2)1
- wherein said 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 second linker;
- X2 does not comprise an Fc region;
- (X1)n is (X1)0 or (X1)1;
- and
- (X2)n is (X2)0 or (X2)1;
- wherein the first and second X1 linker are the same or different;
- wherein the first X1 linker is not CH1 and/or the second X1 linker is not CL;
- wherein the pair of antigens is TNF and PGE2 or VEGF and DLL4, and
- wherein the heavy chain VD1 and VD2 independently comprise three. CDRs from NO:
- 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, or 302;
- and the light chain VD1 and VD2 independently comprise SEQ ID NO:
- 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, or 303.
21 more elements
A binding protein that binds two antigens comprising four polypeptide chains, wherein two polypeptide chains comprise VD1-(X1)n-VD2-C—(X2)n, wherein
- VD1 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 first linker;
- X2 is an Fc region;
- (X1)n is (X1)1 or (X1)1;
- and
- (X2)n is (X2)1 or (X2)1;
- wherein two polypeptide chains comprise 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 second linker;
- X2 does not comprise an Fc region;
- (X1)n is (X1)0 or (X1)1;
- and
- (X2)n is (X2)0 or (X2)1;
- wherein the first and second X1 linker are the same or different;
- wherein the first X1 linker is not CH1 and/or the second X1 linker is not CL;
- wherein the pair of antigens is TNF and PGE2 or VEGF and DLL4, and
- wherein the heavy chain VD1 and VD2 independently comprise three CDRs from SEQ ID NO:
- 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, or 302;
- and the light chain VD1 and VD2 independently comprise SEQ ID NO:
- 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, or 303.
21 more elements
Dependencies are inferred from the claim text.