Methods for identifying antibodies with reduced immunogenicity
AssigneeAbbVie Biotherapeutics Inc.
InventorsFiona A. HARDING, Olivia Jennifer Razo
Life of this patent
Estimating the term…
Abstract
The disclosure describes methods of identifying a variant of a reference antibody with reduced immunogenicity as compared to the reference antibody. The disclosure further describes variants of a reference anti-TNF-α antibody having reduced immunogenicity as compared to the reference anti-TNF-α reference antibody.
Claims25
A method of identifying a variant of a reference antibody with reduced immunogenicity, comprising the steps of:
- (a) contacting a host cell library with an anti-idiotypic antibody that specifically binds to a reference antibody, said reference antibody being a monoclonal antibody that binds to a target molecule, said host cell library comprising mammalian host cells that each express on the cell surface an antibody variant differing from the reference antibody by a single amino acid point mutation;
- (b) identifying a population of cells in said host cell library that express antibody variants that display decreased binding to the anti-idiotypic antibody relative to the reference antibody;
- and
- (c) identifying an antibody variant that is enriched in said population,
- thereby identifying a variant of a reference antibody with reduced immunogenicity.
2-27. (canceled)
A variant of a reference anti-TNF-α antibody or a reference anti-TNF-α binding fragment of an antibody, which reference antibody or binding fragment comprises six complementarity determining regions (“CDRs”) having amino acid sequences corresponding to SEQ ID NO:5 (CDR-H1), SEQ ID NO:6 (CDR-H2), SEQ ID NO:7 (CDR-H3), SEQ ID NO:8 (CDR-L1), SEQ ID NO:9 (CDR-L2) and SEQ ID NO:10 (CDR-H3), wherein the variant comprises at least one substitution selected from G5F in CDR-L1, G5I in CDR-L1, G5V in CDR-L1, G5W in CDR-L1, G5Y in CDR-L1, R7I in CDR-L1, R7T in CDR-L1, R7V in CDR-L1, N8A in CDR-L1, N8D in CDR-L1, N8E in CDR-L1, N8G in CDR-L1, N8L in CDR-L1, N8M in CDR-L1, N8Q in CDR-L1, N8R in CDR-L1, N8T in CDR-L1, A1I in CDR-L2, A1T in CDR-L2, A1V in CDR-L2, T4D in CDR-L2, R2G in CDR-L3, N4F in CDR-L3, N4M in CDR-L3, N4W in CDR-L3, N4Y in CDR-L3, R5L in CDR-L3, R5N in CDR-L3, R5W in CDR-L3, R5Y in CDR-L3, T9Y in CDR-L3, D1S in CDR-H1, Y2A in CDR-H1, Y2C in CDR-H1, Y2K in CDR-H1, Y2M in CDR-H1, Y2R in CDR-H1, Y2S in CDR-H1, Y2V in CDR-H1, H5C in CDR-H1, H5D in CDR-H1, H5E in CDR-H1, H5S in CDR-H1, H5T in CDR-H1, T3A in CDR-H2, T3G in CDR-H2, T3N in CDR-H2, W4A in CDR-H2, W4F in CDR-H2, W4H in CDR-H2, W4L in CDR-H2, W4M in CDR-H2, W4V in CDR-H2, N5G in CDR-H2, S6D in CDR-H2, S6L in CDR-H2, I9K in CDR-H2, DIOL in CDR-H2, Y11A in CDR-H2, Y11C in CDR-H2, Y11E in CDR-H2, Y11F in CDR-H2, Y11G in CDR-H2, Y11H in CDR-H2, Y11I in CDR-H2, Y11K in CDR-H2, Y11L in CDR-H2, Y11M in CDR-H2, Y11N in CDR-H2, Y11Q in CDR-H2, Y11R in CDR-H2, Y11S in CDR-H2, Y11V in CDR-H2, Y 11W in CDR-H2, A12Y in CDR-H2, D13N in CDR-H2, V15D in CDR-H2, V15L in CDR-H2, V15M in CDR-H2, V15Q in CDR-H2, V15T in CDR-H2, E16F in CDR-H2, E16H in CDR-H2, E16K in CDR-H2, E16R in CDR-H2, E16T in CDR-H2, E16W in CDR-H2, G17A in CDR-H2, G17C in CDR-H2, G17E in CDR-H2, G17H in CDR-H2, G17I in CDR-H2, G17K in CDR-H2, G17L in CDR-H2, G17M in CDR-H2, G17N in CDR-H2, G17P in CDR-H2, G17Q in CDR-H2, G17R in CDR-H2, G17S in CDR-H2, G17T in CDR-H2, G17Y in CDR-H2, V1G in CDR-H3, V1R in CDR-H3, V1W in CDR-H3, L4T in CDR-H3, L4V in CDR-H3, T6V in CDR-H3, S9K in CDR-H3, S9W in CDR-H3, S9Y in CDR-H3, and D11V in CDR-H3,
- wherein the six CDRs altogether have up to 8 amino acid substitutions as compared to CDR sequences of the reference antibody or binding fragment.
(canceled)
Dependencies are inferred from the claim text.