Antibodies to TNFα
Provided herein are antibodies, antigen binding portions, and derivatives thereof that are capable of binding tumor necrosis factor alpha (TNFα); nucleic acids encoding the antibodies, antigen binding portions, and derivatives thereof, including complementary nucleic acids; vectors; and host cells containing the nucleic acids.
1. An antibody capable of binding TNF-α, or an antigen binding portion thereof, which comprises, wherein the antibody is selected from the group consisting of:
(A) an antibody which comprises:
(a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (V H ) comprising the amino acid sequence SEQ ID NO:271; and
(b) a light chain, wherein the light chain comprises a light chain variable region (V L ) comprising the amino acid sequence SEQ ID NO:272; and
(B) an antibody which comprises:
(a) a heavy chain, wherein the heavy chain comprises a heavy chain variable region (V H ) comprising the amino acid sequence SEQ ID NO:453; and
(b) a light chain, wherein the light chain comprises a light chain variable region (V L ) comprising the amino acid sequence SEQ ID NO:454.
2. The antibody of claim 1 or the antigen binding portion thereof which comprises the V H comprising the amino acid sequence SEQ ID NO:271 and the V L comprising the amino acid sequence SEQ ID NO:272, wherein the heavy chain comprises the amino acid sequence SEQ ID NO:269.
3. The antibody of claim 1 or the antigen binding portion thereof which comprises the V H comprising the amino acid sequence SEQ ID NO: 271 and the V L comprising the amino acid sequence SEQ ID NO:272, wherein the light chain comprises the amino acid sequence SEQ ID NO:270.
4. The antibody of claim 1 or the antigen binding portion thereof which comprises the V H comprising the amino acid sequence SEQ ID NO:453 and the V L comprising the amino acid sequence SEQ ID NO:454, wherein the heavy chain comprises the amino acid sequence SEQ ID NO:451.
5. The antibody of claim 1 or the antigen binding portion thereof which comprises the V H comprising the amino acid sequence SEQ ID NO:453 and the V L comprising the amino acid sequence SEQ ID NO:454, wherein the light chain comprises the amino acid sequence SEQ ID NO:452.
6. The antigen binding portion of the antibody of claim 1 , wherein the antigen binding portion is selected from the group consisting of an Fab fragment, an F(ab′) 2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region, an Fd fragment consisting of the VH and CH1 domains, an Fv fragment consisting of the VL and VH domains of a single arm of the antibody, a dAb fragment consisting of the V H domain, and an scFv.
7. The antibody of claim 1 or the antigen binding portion thereof, which is humanized.
8. A pharmaceutical composition comprising:
(a) the antibody of claim 1 or the antigen binding portion thereof; and
(b) a pharmaceutically acceptable carrier.
9. A nucleic acid molecule which encodes the antibody of claim 1 or the antigen binding portion thereof.
10. An expression vector comprising the nucleic acid molecule of claim 9 .
11. A host cell comprising a nucleic acid molecule which encodes the antibody of claim 1 or the antigen binding portion thereof.
12. A method for the production of an antibody or an antigen binding portion thereof, comprising:
(a) culturing of the host cell of claim 11 in a culture medium under conditions which permit expression of the antibody or binding portion thereof and its secretion into the culture medium; and
(b) recovering the antibody or binding portion thereof from the culture medium.
13. The pharmaceutical composition of claim 8 , wherein the antibody or the antigen binding portion thereof comprises the V H comprising the amino acid sequence SEQ ID NO:271 and the V L comprising the amino acid sequence SEQ ID NO:272, wherein the heavy chain comprises the amino acid sequence SEQ ID NO:269.
14. The pharmaceutical composition of claim 8 , wherein the antibody or the antigen binding portion thereof comprises the V H comprising the amino acid sequence SEQ ID NO: 271 and the V L comprising the amino acid sequence SEQ ID NO:272, wherein the light chain comprises the amino acid sequence SEQ ID NO:270.
15. The pharmaceutical composition of claim 8 , wherein the antibody or the antigen binding portion thereof comprises the V H comprising the amino acid sequence SEQ ID NO:453 and the V L comprising the amino acid sequence SEQ ID NO:454, wherein the heavy chain comprises the amino acid sequence SEQ ID NO:451.
16. The pharmaceutical composition of claim 8 , wherein the antibody or the antigen binding portion thereof comprises the V H comprising the amino acid sequence SEQ ID NO:453 and the V L comprising the amino acid sequence SEQ ID NO:454, wherein the light chain comprises the amino acid sequence SEQ ID NO:452.
17. The pharmaceutical composition of claim 8 , wherein the antigen binding portion is selected from the group consisting of an Fab fragment, an F(ab′) 2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region, an Fd fragment consisting of the VH and CH1 domains, an Fv fragment consisting of the VL and VH domains of a single arm of the antibody, a dAb fragment consisting of the V H domain, and an scFv.
18. The pharmaceutical composition of claim 8 , wherein the antibody or the antigen binding portion thereof is humanized.