Antibodies to TNF Alpha
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 isolated antibody or antigen binding portion thereof capable of binding TNF-α wherein, either:
(a) the V H (variable heavy chain) antibody chain comprises CDR1, CDR2 and CDR3 regions whose sequences are identified by SEQ ID NO: 43, 44, and 45 respectively and wherein the V L (variable light chain) antibody chain comprises CDR1, CDR2 and CDR3 regions whose sequences are identified by SEQ ID NO: 49, 50 and 51, respectively, excluding an isolated antibody or antigen binding portion thereof capable of binding TNF-α wherein the V H antibody chain comprises CDR1, CDR2 and CDR3 regions whose sequences are identified by SEQ ID NO: 46, 47, and 48 respectively and wherein the V L antibody chain comprises at least one of the V L CDR1, CDR2 and CDR3 regions whose sequences are identified by SEQ ID NO: 52, 53 and 54, respectively;
(b) the V H antibody chain comprises CDR1, CDR2 and CDR3 regions whose sequences are identified by SEQ ID NO: 43, 44, and 45 respectively and wherein the V L antibody chain comprises CDR1, CDR2 and CDR3 regions whose sequences are identified by SEQ ID NO: 49, 50 and 51, respectively, and wherein the heavy chain V H region has a G at position 30;
(c) the V H antibody chain comprises a sequence selected from the group consisting of SEQ ID NO: 21, 22, 23, 24, 25 and 26, excluding sequences identified by SEQ ID NO: 40;
(d) the V H antibody chain comprises the sequence identified by SEQ ID NO: 23;
(e) the V H antibody chain comprises the sequence identified by SEQ ID NO: 24;
(f) V H and V L antibody chains comprise a sequence selected from the group consisting of SEQ ID NOs: 149, 265, 271, 291, 295, 303, 309, 313, 321, 359, 401, 402 and 453 and selected from the group consisting of SEQ ID NOs: 150, 266, 272, 292, 296, 304, 310, 314, 322, 360 and 454, respectively; or
(g) antibody heavy and light chains comprise a sequence selected from the group consisting of SEQ ID NOs: 147, 263, 269, 289, 293, 301, 307, 311, 319, 357, 373 and 399 and selected from the group consisting of SEQ ID NOs: 148, 264, 270, 290, 294, 302, 308, 312, 320, 358, 374 and 400, respectively.
2 . The isolated antibody or antigen binding portion thereof of claim 1 , wherein the antibody is a bispecific antibody.
3 . The isolated antibody or antigen binding portion thereof of claim 1 , wherein the V H antibody chain comprises the sequence identified by SEQ ID NO: 23 and wherein the V L antibody chain comprises the sequence identified by SEQ ID NO: 37 or SEQ ID NO: 38.
4 . The isolated antibody or antigen binding portion thereof of claim 1 , wherein the V H antibody chain comprises the sequence identified by SEQ ID NO: 24 and wherein the V L antibody chain comprises the sequence identified by SEQ ID NO: 37 or SEQ ID NO: 38.
5 . A nucleic acid encoding the isolated antibody or antigen binding portion thereof of claim 1 .
6 . A vector comprising a nucleic acid according to claim 5 .
7 . A host cell comprising a nucleic acid according to claim 5 .
8 . A method for the production of an isolated antibody or antigen binding portion thereof, said method comprising culturing of a host cell of claim 7 under conditions allowing the expression of the antibody or binding portion thereof and recovering the antibody or binding portion thereof from the culture.
9 . A pharmaceutical composition comprising an isolated antibody or antigen binding portion thereof of claim 1 .