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US 2011/0212094 A1Published application
Dual variable domain immunoglobulins and uses thereof
AssigneeAbbott Laboratories
InventorsTariq Ghayur, Jochen G. Salfeld, Michael J. McPherson, Maria C. Harris, Junjian Liu, Peter C. Isakson, Jijie Gu
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.
Claims76
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;
- 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;
- and
- n is 0 or 1;
- wherein the binding protein binds a pair of antigens selected from the group consisting of TNF (seq. 2) and NGF;
- TNF (seq. 3) and NGF;
- TNF (seq. 4) and NGF;
- TNF (seq. 5) and NGF;
- TNF (seq. 6) and NGF;
- TNF (seq. 2) and SOST;
- TNF (seq. 3) and SOST;
- TNF (seq. 4) and SOST;
- TNF (seq. 5) and SOST;
- TNF (seq. 6) and SOST;
- TNF (seq. 2) and PGE2;
- TNF (seq. 3) and PGE2;
- TNF (seq. 4) and PGE2;
- TNF (seq. 5) and PGE2;
- TNF (seq. 6) and PGE2;
- TNF (seq. 1) and LPA;
- TNF (seq. 2) and LPA;
- TNF (seq. 3) and LPA;
- TNF (seq. 4) and LPA;
- TNF (seq. 5) and LPA;
- and TNF (seq. 6) and LPA.
25 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 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 CH1;
- X2 does not comprise an Fc region;
- and
- n is 0 or 1;
- wherein the binding protein binds a pair of antigens selected from the group consisting of TNF (seq. 2) and NGF;
- TNF (seq. 3) and NGF;
- TNF (seq. 4) and NGF;
- TNF (seq. 5) and NGF;
- TNF (seq. 6) and NGF;
- TNF (seq. 2) and SOST;
- TNF (seq. 3) and SOST;
- TNF (seq. 4) and SOST;
- TNF (seq. 5) and SOST;
- TNF (seq. 6) and SOST;
- TNF (seq. 2) and PGE2;
- TNF (seq. 3) and PGE2;
- TNF (seq. 4) and PGE2;
- TNF (seq. 5) and PGE2;
- TNF (seq. 6) and PGE2;
- TNF (seq. 1) and LPA;
- TNF (seq. 2) and LPA;
- TNF (seq. 3) and LPA;
- TNF (seq. 4) and LPA;
- TNF (seq. 5) and LPA;
- and TNF (seq. 6) and LPA.
25 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;
- 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;
- and
- X2 is an Fc region;
- 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;
- 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 CH1;
- X2 does not comprise an Fc region;
- and
- n is 0 or 1, wherein the binding protein binds a pair of antigens selected from the group consisting of TNF (seq. 2) and NGF;
- TNF (seq. 3) and NGF;
- TNF (seq. 4) and NGF;
- TNF (seq. 5) and NGF;
- TNF (seq. 6) and NGF;
- TNF (seq. 2) and SOST;
- TNF (seq. 3) and SOST;
- TNF (seq. 4) and SOST;
- TNF (seq. 5) and SOST;
- TNF (seq. 6) and SOST;
- TNF (seq. 2) and PGE2;
- TNF (seq. 3) and PGE2;
- TNF (seq. 4) and PGE2;
- TNF (seq. 5) and PGE2;
- TNF (seq. 6) and PGE2;
- TNF (seq. 1) and LPA;
- TNF (seq. 2) and LPA;
- TNF (seq. 3) and LPA;
- TNF (seq. 4) and LPA;
- TNF (seq. 5) and LPA;
- and TNF (seq. 6) and LPA.
32 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 linker with the proviso that it is not CH1;
- and
- X2 is an Fc region;
- and
- 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 linker with the proviso that it is not CH1;
- X2 does not comprise an Fc region;
- and
- n is 0 or 1;
- wherein the VD1 and VD2 heavy 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, and 44 and wherein the VD1 and VD2 light chain variable domains comprise an amino acid sequence selected from the group consisting of SEQ ID NOs:. 29, 31, 33, 35, 37, 39, 41, 43, and 45.
14 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 linker with the proviso that it is not CH1;
- X2 is an Fc region;
- and
- n is 0 or 1;
- and
- 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 linker with the proviso that it is not CH1;
- X2 does not comprise an Fc region;
- and
- n is 0 or 1;
- wherein the DVD-Ig binds at least one antigen selected from the group consisting of TNF (seq. 2);
- TNF (seq. 3);
- TNF (seq. 4);
- TNF (seq. 5);
- TNF (seq. 6);
- NGF;
- SOST;
- PGE2;
- and LPA.
22 more elements
A method for generating a Dual Variable Domain Immunoglobulin that binds two antigens comprising the steps of
- a) obtaining a first parent antibody or antigen binding portion thereof, that binds a first antigen;
- b) obtaining a second parent antibody or antigen binding portion thereof, that binds 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 is a linker with the proviso that it is not CH1;
- X2 is an Fc region;
- and
- n is 0 or 1;
- and
- 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 is a linker with the proviso that it is not CH1;
- X2 does not comprise an Fc region;
- and
- n is 0 or 1;
- and
- e) expressing said first, second, third and fourth polypeptide chains;
- such that a Dual Variable Domain Immunoglobulin that binds said first and said second antigen is generated, wherein the binding protein binds a pair of antigens selected from the group consisting of TNF (seq. 2) and NGF;
- TNF (seq. 3) and NGF;
- TNF (seq. 4) and NGF;
- TNF (seq. 5) and NGF;
- TNF (seq. 6) and NGF;
- TNF (seq. 2) and SOST;
- TNF (seq. 3) and SOST;
- TNF (seq. 4) and SOST;
- TNF (seq. 5) and SOST;
- TNF (seq. 6) and SOST;
- TNF (seq. 2) and PGE2;
- TNF (seq. 3) and PGE2;
- TNF (seq. 4) and PGE2;
- TNF (seq. 5) and PGE2;
- TNF (seq. 6) and PGE2;
- TNF (seq. 1) and LPA;
- TNF (seq. 2) and LPA;
- TNF (seq. 3) and LPA;
- TNF (seq. 4) and LPA;
- TNF (seq. 5) and LPA;
- and TNF (seq. 6) and LPA.
39 more elements
A method for generating a Dual Variable Domain Immunoglobulin that binds two antigens with desired properties comprising the steps of
- a) obtaining a first parent antibody or antigen binding portion thereof, that binds 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, that binds 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 is a linker with the proviso that it is not CH1;
- X2 is an Fc region;
- and
- n is 0 or 1;
- 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 is a linker with the proviso that it is not CH1;
- X2 does not comprise an Fc region;
- and
- n is 0 or 1;
- e) expressing said first, second, third and fourth polypeptide chains;
- such that a Dual Variable Domain Immunoglobulin that binds said first and said second antigen with desired properties is generated, wherein the binding protein binds a pair of antigens selected from the group consisting of TNF (seq. 2) and NGF;
- TNF (seq. 3) and NGF;
- TNF (seq. 4) and NGF;
- TNF (seq. 5) and NGF;
- TNF (seq. 6) and NGF;
- TNF (seq. 2) and SOST;
- TNF (seq. 3) and SOST;
- TNF (seq. 4) and SOST;
- TNF (seq. 5) and SOST;
- TNF (seq. 6) and SOST;
- TNF (seq. 2) and PGE2;
- TNF (seq. 3) and PGE2;
- TNF (seq. 4) and PGE2;
- TNF (seq. 5) and PGE2;
- TNF (seq. 6) and PGE2;
- TNF (seq. 1) and LPA;
- TNF (seq. 2) and LPA;
- TNF (seq. 3) and LPA;
- TNF (seq. 4) and LPA;
- TNF (seq. 5) and LPA;
- and TNF (seq. 6) and LPA.
37 more elements
Dependencies are inferred from the claim text.