Bispecific antibody specifically binding to IL-17A and TNF-α
Inventors
Yoon, Jae Bong • JEON, Eun Young • Baek, Gi Sun • Yoo, Seok Ho • Park, Bum-Chan • Park, Young Woo
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12139530-B2
Publication Date
2024-11-12
Expiration Date
Abstract
A bispecific antibody according to an embodiment of the present disclosure specifically binds to IL-17A and TNF-α. The bispecific antibody according to the present invention or an antigen binding fragment thereof exhibits high specificity for IL-17A and TNF-α and more favorable neutralization property compared to monospecific antibody of a prior art, and, by quickly suppressing inflammation and an immune response by inhibiting simultaneously IL-17 and TNF-α, it has an advantage of improving the treatment effect with lower dose.
Core Innovation
The invention relates to a bispecific antibody specifically binding to IL-17A and TNF-b1, where one binding component specifically binds IL-17A or an antigen binding fragment thereof and the other binding component specifically binds TNF-b1 or an antigen binding fragment thereof. The IL-17A-binding component and the TNF-b1-binding component are characterized by defined heavy chain CDR sequences and defined light chain CDR sequences, including heavy chain CDR1 of SEQ ID NO: 1 or 8, heavy chain CDR2 selected among SEQ ID NOs: 2, 4, 9, or 11, and heavy chain CDR3 selected among SEQ ID NOs: 3, 5, 6, 7, or 10, together with light chain CDR1 of SEQ ID NO: 12, light chain CDR2 of SEQ ID NO: 13, and light chain CDR3 of SEQ ID NO: 14.
The disclosed concept includes construct and sequence-characterization using specified IL-17A-targeted heavy-chain CDRs and IL-17A light-chain CDRs, together with broader framework and variable-region options. The construct strategy uses an IL-17A scFv fused to the C-terminus region of a TNF-b1 antibody with a linker, and provides an expression context in HEK293F. The patent text further characterizes additional properties including FcRn affinity comparable to IgG and Fc interactions relevant to ADCC, including binding to CD64 and CD16a.
The patent text reports evaluations of co-binding and neutralization using IL-17 and TNF-b1 reporter systems and comparative monospecific references, including Humira and secukinumab, and comparison to a prior bispecific LY3114062. Additional reported data include maintained efficacy across purification and production systems, including GFC versus CEX and HEK293F versus CHO-S. The in vivo context described uses IL-17A+TNF-b1 stimulation in C57BL/6 mice and reports reduction of KC (CXCL1), with SDA-0070 showing the lowest KC level among tested groups.
Claims Coverage
Independent claim clm-00001 defines a bispecific antibody that specifically binds IL-17A and TNF-b1, with the IL-17A- and TNF-b1-binding antigen-binding components characterized by a specific set of heavy-chain and light-chain CDR sequence selections. The remaining inventive features are additional sequence and architecture limitations introduced in dependent claims.
Bispecific antibody binding IL-17A and TNF-b1 with defined heavy and light chain CDRs
A bispecific antibody specifically binding IL-17A and TNF-b1 comprising an antibody specifically binding to IL-17A or an antigen binding fragment thereof and an antibody specifically binding to TNF-b1 or an antigen binding fragment thereof, where the antibody specifically binding to IL-17A comprises heavy chain CDR1 of SEQ ID NO: 1 or 8, heavy chain CDR2 selected from SEQ ID NOs: 2, 4, 9, or 11, heavy chain CDR3 selected from SEQ ID NOs: 3, 5, 6, 7, or 10, and light chain CDR1 of SEQ ID NO: 12, light chain CDR2 of SEQ ID NO: 13, and light chain CDR3 of SEQ ID NO: 14.
C-terminus linkage between IL-17A heavy-chain constant region and TNF-b1 heavy-chain constant region
The bispecific antibody specifically binds IL-17A and TNF-b1, where the C-terminus of the IL-17A heavy-chain constant region is linked to the C-terminus of the TNF-b1 heavy-chain constant region.
Antigen-binding fragment defined as an scFv single-chain variable fragment
The bispecific antibody specifically binds IL-17A and TNF-b1, where its antigen-binding fragment is an scFv single-chain variable fragment.
IL-17A heavy-chain variable region framework region selected from SEQ ID NO: 15 to SEQ ID NO: 26
The bispecific antibody specifically binds IL-17A and TNF-b1, where its heavy chain variable region framework region is selected from SEQ ID NO: 15 to SEQ ID NO: 26.
Light-chain variable region framework region selected from SEQ ID NO: 27 to SEQ ID NO: 33
The bispecific antibody specifically binds IL-17A and TNF-b1, where its light chain variable region framework region is selected from the group consisting of SEQ ID NO: 27 to SEQ ID NO: 33.
Pharmaceutical composition for treating an autoimmune disease
A pharmaceutical composition for treating an autoimmune disease that includes a bispecific antibody or an antigen-binding fragment of that antibody as an active ingredient.
Overall, the claim set centers on a bispecific antibody with IL-17A and TNF-b1 binding defined by specified heavy-chain and light-chain CDR sequence options. Dependent coverage refines the binding agent by specifying framework-region sequence selections and the antigen-binding fragment format, and adds formulation scope for a pharmaceutical composition directed to autoimmune disease.
Stated Advantages
High specificity binding is stated, with no detectable off-target binding to other IL-17 family members or unrelated proteins.
FcRn affinity comparable to IgG.
ADCC-relevant Fc interactions via binding to CD64 and CD16a are reported.
SDA-0070 shows maintained efficacy across purification and production systems, including GFC versus CEX and HEK293F versus CHO-S.
In vivo KC (CXCL1) reduction after IL-17A+TNF-b1 stimulation, with SDA-0070 showing the lowest KC level among tested groups.
Documented Applications
Reduction of KC (CXCL1) in C57BL/6 mice after IL-17A+TNF-b1 stimulation is described, including that SDA-0070 shows the lowest KC level among tested groups.
A pharmaceutical composition for treating an autoimmune disease is described, with a bispecific antibody or antigen-binding fragment as an active ingredient.
Interested in licensing this patent?