Humanization of rabbit antibodies using a universal antibody framework
US-11858981-B2 · Jan 2, 2024 · US
US9534046B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9534046-B2 |
| Application number | US-201514695949-A |
| Country | US |
| Kind code | B2 |
| Filing date | Apr 24, 2015 |
| Priority date | Dec 31, 2007 |
| Publication date | Jan 3, 2017 |
| Grant date | Jan 3, 2017 |
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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.
Opening claim text (preview).
The invention claimed is: 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.
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