OPTIMIZED ANTI-TL1A ANTIBODIES
Described herein are humanized anti-TL1A antibodies and pharmaceutical compositions for the treatment of inflammatory bowel disease (IBD), such as Crohn's Disease (CD) and ulcerative colitis (UC).
1 . A nucleic acid encoding an antibody, or antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the nucleic acid comprises:
a nucleic acid sequence encoding a heavy chain variable region comprising: (a) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (b) a nucleic acid encoding a HCDR2 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 554 to 564, or 574 to 577; and (c) a nucleic acid encoding a HCDR3 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 565 to 568, or 579 to 581; and
a nucleic acid sequence encoding a light chain variable region comprising: (a) a nucleic acid encoding a LCDR1 comprising an amino acid sequence set forth by any one of SEQ ID NOs: 569 or 570; (b) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (c) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572.
2 . The nucleic acid encoding the antibody or antigen binding portion of claim 1 , wherein the HCDR2 comprises the amino acid sequence as set forth by SEQ ID NO: 554.
3 . The nucleic acid encoding the antibody or antigen binding portion of claim 1 , wherein the HCDR2 comprises the amino acid sequence as set forth by SEQ ID NO: 555.
4 . The nucleic acid encoding the antibody or antigen binding portion of claim 1 , wherein the HCDR3 comprises the amino acid sequence as set forth by SEQ ID NO: 565.
5 . The nucleic acid encoding the antibody or antigen binding portion of claim 1 , wherein the HCDR3 comprises the amino acid sequence as set forth by SEQ ID NO: 566.
6 . The nucleic acid encoding the antibody or antigen binding portion of claim 1 , wherein the LCDR1 comprises the amino acid sequence as set forth by SEQ ID NO: 569.
7 . The nucleic acid encoding the antibody or antigen binding portion of claim 1 , wherein the nucleic acid sequence encoding the heavy chain variable region comprises a nucleic acid encoding for a heavy chain constant region, and the nucleic acid sequence encoding the light chain variable region comprises a nucleic acid encoding for a light chain constant region.
8 . A recombinant vector comprising the nucleic acid of claim 1 .
9 . The recombinant vector of claim 8 , wherein the recombinant vector is a plasmid.
10 . The recombinant vector of claim 8 , wherein the recombinant vector is an expression vector.
11 . A host cell comprising the recombinant vector of claim 8 .
12 . A nucleic acid encoding an antibody, or antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the nucleic acid comprises:
a nucleic acid sequence encoding a heavy chain variable region comprising: (a) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (b) a nucleic acid encoding a HCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 554; and (c) a nucleic acid encoding a HCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 565; and
a nucleic acid sequence encoding a light chain variable region comprising: (a) a nucleic acid encoding a LCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 569; (b) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (c) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572.
13 . The nucleic acid encoding the antibody or antigen binding portion of claim 12 , wherein the nucleic acid sequence encoding the heavy chain variable region comprises a nucleic acid encoding for a heavy chain constant region, and the nucleic acid sequence encoding the light chain variable region comprises a nucleic acid encoding for a light chain constant region.
14 . A recombinant vector comprising the nucleic acid of claim 12 .
15 . The recombinant vector of claim 14 , wherein the recombinant vector is a plasmid.
16 . The recombinant vector of claim 14 , wherein the recombinant vector is an expression vector.
17 . A host cell comprising the recombinant vector of claim 14 .
18 . A method of producing an antibody, or an antigen binding portion thereof, that binds to tumor necrosis factor-like ligand 1A (TL1A), wherein the method comprises
(a) providing a host cell comprising an expression vector harboring a nucleic acid encoding the antibody, or the antibody binding portion thereof, wherein the nucleic acid comprises:
a nucleic acid sequence encoding a heavy chain variable region comprising: (i) a nucleic acid encoding a HCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 553; (ii) a nucleic acid encoding a HCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 554; and (iii) a nucleic acid encoding a HCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 565; and
a nucleic acid sequence encoding a light chain variable region comprising: (i) a nucleic acid encoding a LCDR1 comprising the amino acid sequence set forth by SEQ ID NO: 569; (ii) a nucleic acid encoding a LCDR2 comprising the amino acid sequence set forth by SEQ ID NO: 488; and (iii) a nucleic acid encoding a LCDR3 comprising the amino acid sequence set forth by SEQ ID NO: 572; and
(b) culturing the host cell under conditions to induce expression of the antibody or antibody portion from the host cell.
19 . The method of claim 18 , further comprising harvesting the antibody or antigen binding portion.
20 . The method of claim 19 , further comprising purifying the harvested antibody or antigen binding portion.