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US 2010/0076178 A1Published application
Dual Variable Domain Immumoglobulins and Uses Thereof
AssigneeAbbott Laboratories
InventorsTariq Ghayur, Susan E. Morgan-Lappe, Edward B. Reilly, Gillian A. Kingsbury, Andrew Phillips, Jieyi Wang, Randy L. Bell, Suzanne M. Norvell, Yingchun Li, Junjian Liu, Hua Ying
Life of this patent
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Abstract
The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention, diagnosis, and/or treatment of disease.
Claims40
A binding protein comprising a polypeptide chain, wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n, wherein;
- VD1 is a first heavy chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second heavy chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a heavy chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent,
- wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of CD-20 and CD-19;
- CD-20 and CD-80;
- CD-20 and CD-22;
- CD-20 and CD-40;
- CD-3 and HER-2;
- CD-3 and CD-19;
- EGFR and HER-2;
- EGFR and CD-3;
- EGFR and IGF1,2;
- EGFR and IGF1R;
- EGFR and RON;
- EGFR and HGF;
- EGFR and c-MET;
- HER-2 and IGF1,2;
- HER-2 and IGF1R;
- RON and HGF;
- VEGF and EGFR;
- VEGF and HER-2;
- VEGF and CD-20;
- VEGF and IGF1,2;
- VEGF and DLL4;
- VEGF and HGF;
- VEGF and RON;
- VEGF and NRP1;
- CD-20 and CD3;
- DLL-4 and PLGF;
- VEGF and PLGF, ErbB3 and EGFR, HER-2 and ErbB3, ErbB3 and HGF;
- HER-2 and PLGF, and HER-2 and HER-2.
31 more elements
A binding protein comprising a polypeptide chain, wherein said polypeptide chain comprises VD1-(X1)n-VD2-C-(X2)n, wherein;
- VD1 is a light heavy chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a light heavy chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a light chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent,
- wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of CD-20 and CD-19;
- CD-20 and CD-80;
- CD-20 and CD-22;
- CD-20 and CD-40;
- CD-3 and HER-2;
- CD-3 and CD-19;
- EGFR and HER-2;
- EGFR and CD-3;
- EGFR and IGF1,2;
- EGFR and IGF1R;
- EGFR and RON;
- EGFR and HGF;
- EGFR and c-MET;
- HER-2 and IGF1,2;
- HER-2 and IGF1R;
- RON and HGF;
- VEGF and EGFR;
- VEGF and HER-2;
- VEGF and CD-20;
- VEGF and IGF1,2;
- VEGF and DLL4;
- VEGF and HGF;
- VEGF and RON;
- VEGF and NRP1;
- CD-20 and CD3;
- DLL-4 and PLGF;
- VEGF and PLGF, ErbB3 and EGFR, HER-2 and ErbB3, ErbB3 and HGF;
- HER-2 and PLGF, and HER-2 and HER-2.
31 more elements
A binding protein 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 obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second heavy chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a heavy chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent;
- and
- wherein said second polypeptide chain comprises a second VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first light chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second light chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a light chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n does not comprise an Fc region, wherein said (X2)n is either present or absent, wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of CD-20 and CD-19;
- CD-20 and CD-80;
- CD-20 and CD-22;
- CD-20 and CD-40;
- CD-3 and HER-2;
- CD-3 and CD-19;
- EGFR and HER-2;
- EGFR and CD-3;
- EGFR and IGF1,2;
- EGFR and IGF1R;
- EGFR and RON;
- EGFR and HGF;
- EGFR and c-MET;
- HER-2 and IGF1,2;
- HER-2 and IGF1R;
- RON and HGF;
- VEGF and EGFR;
- VEGF and HER-2;
- VEGF and CD-20;
- VEGF and IGF1,2;
- VEGF and DLL4;
- VEGF and HGF;
- VEGF and RON;
- VEGF and NRP1;
- CD-20 and CD3;
- DLL-4 and PLGF;
- VEGF and PLGF, ErbB3 and EGFR, HER-2 and ErbB3, ErbB3 and HGF;
- HER-2 and PLGF, and HER-2 and HER-2.
39 more elements
A DVD-Ig capable of binding two antigens comprising four polypeptide chains, wherein first and third polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first heavy chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second heavy chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a heavy chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent;
- and
- wherein second and fourth polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first light chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second light chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a light chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n does not comprise an Fc region, wherein said (X2)n is either present or absent, wherein the VD1 and VD2 heavy chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 27, 29, 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, and 93 and wherein the VD1 and VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 28, 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, and 94.
13 more elements
A DVD-Ig capable of binding two antigens comprising four polypeptide chains, wherein first and third polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first heavy chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second heavy chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a heavy chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent;
- and
- wherein second and fourth polypeptide chains comprise VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first light chain variable domain obtained from a first parent antibody or antigen binding portion thereof;
- VD2 is a second light chain variable domain obtained from a second parent antibody or antigen binding portion thereof;
- C is a light chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n does not comprise an Fc region, wherein said (X2)n is either present or absent, wherein the DVD-Ig binds at least one antigen selected from the group consisting of CD-20, CD-19, CD-80, CD-22, CD-40, CD-3, HER-2, EGFR, IGF1,2, IGF1R, RON, HGF, c-MET, VEGF, DLL4, NRP1, PLGF, and ErbB3.
11 more elements
A method for generating a Dual Variable Domain Immunoglobulin capable of binding two antigens comprising the steps of
- a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding a first antigen;
- b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding a second antigen;
- c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first heavy chain variable domain obtained from said first parent antibody or antigen binding portion thereof;
- VD2 is a second heavy chain variable domain obtained from said second parent antibody or antigen binding portion thereof;
- C is a heavy chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent;
- d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein
- VD1 is a first light chain variable domain obtained from said first parent antibody or antigen binding portion thereof;
- VD2 is a second light chain variable domain obtained from said second parent antibody or antigen binding thereof;
- C is a light chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n does not comprise an Fc region, wherein said (X2)n is either present or absent;
- e) expressing said first, second, third and fourth polypeptide chains;
- such that a Dual Variable Domain Immunoglobulin capable of binding said first and said second antigen is generated, wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of CD-20 and CD-19;
- CD-20 and CD-80;
- CD-20 and CD-22;
- CD-20 and CD-40;
- CD-3 and HER-2;
- CD-3 and CD-19;
- EGFR and HER-2;
- EGFR and CD-3;
- EGFR and IGF1,2;
- EGFR and IGF1R;
- EGFR and RON;
- EGFR and HGF;
- EGFR and c-MET;
- HER-2 and IGF1,2;
- HER-2 and IGF1R;
- RON and HGF;
- VEGF and EGFR;
- VEGF and HER-2;
- VEGF and CD-20;
- VEGF and IGF1,2;
- VEGF and DLL4;
- VEGF and HGF;
- VEGF and RON;
- VEGF and NRP1;
- CD-20 and CD3;
- DLL-4 and PLGF;
- VEGF and PLGF, ErbB3 and EGFR, HER-2 and ErbB3, ErbB3 and HGF;
- HER-2 and PLGF, and HER-2 and HER-2.
42 more elements
A method for generating a Dual Variable Domain Immunoglobulin capable of binding two antigens with desired properties comprising the steps of
- a) obtaining a first parent antibody or antigen binding portion thereof, capable of binding a first antigen and possessing at least one desired property exhibited by the Dual Variable Domain Immunoglobulin;
- b) obtaining a second parent antibody or antigen binding portion thereof, capable of binding a second antigen and possessing at least one desired property exhibited by the Dual Variable Domain Immunoglobulin;
- c) constructing first and third polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein;
- VD1 is a first heavy chain variable domain obtained from said first parent antibody or antigen binding portion thereof;
- VD2 is a second heavy chain variable domain obtained from said second parent antibody or antigen binding portion thereof;
- C is a heavy chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n is an Fc region, wherein said (X2)n is either present or absent;
- d) constructing second and fourth polypeptide chains comprising VD1-(X1)n-VD2-C-(X2)n, wherein;
- VD1 is a first light chain variable domain obtained from said first parent antibody or antigen binding portion thereof;
- VD2 is a second light chain variable domain obtained from said second parent antibody or antigen binding portion thereof;
- C is a light chain constant domain;
- (X1)n is a linker with the proviso that it is not CH1, wherein said (X1)n is either present or absent;
- and
- (X2)n does not comprise an Fc region, wherein said (X2)n is either present or absent;
- e) expressing said first, second, third and fourth polypeptide chains;
- such that a Dual Variable Domain Immunoglobulin capable of binding said first and said second antigen with desired properties is generated, wherein the binding protein is capable of binding a pair of antigens selected from the group consisting of CD-20 and CD-19;
- CD-20 and CD-80;
- CD-20 and CD-22;
- CD-20 and CD-40;
- CD-3 and HER-2;
- CD-3 and CD-19;
- EGFR and HER-2;
- EGFR and CD-3;
- EGFR and IGF1,2;
- EGFR and IGF1R;
- EGFR and RON;
- EGFR and HGF;
- EGFR and c-MET;
- HER-2 and IGF1,2;
- HER-2 and IGF1R;
- RON and HGF;
- VEGF and EGFR;
- VEGF and HER-2;
- VEGF and CD-20;
- VEGF and IGF1,2;
- VEGF and DLL4;
- VEGF and HGF;
- VEGF and RON;
- VEGF and NRP1;
- CD-20 and CD3;
- DLL-4 and PLGF;
- VEGF and PLGF, ErbB3 and EGFR, HER-2 and ErbB3, ErbB3 and HGF;
- HER-2 and PLGF, and HER-2 and HER-2.
42 more elements
Dependencies are inferred from the claim text.