IL-23 and TNF-alpha binding bi-specific heavy chain polypeptides

Inventors

Crowe, Scott • Cubitt, Marion • Carlton, Tim • Maggiore, Luana • DUARTE, Lurdes • Roberts, Kevin • West, Mike

Assignees

Sorriso Pharmaceuticals Inc

Abstract

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain which binds to IL-23, wherein the immunoglobulin chain variable domain comprises three complementarity determining regions (CDR1-CDR3) and four framework regions (FR1-FR4), wherein CDR1 comprises a sequence sharing 60% or greater sequence identity with SEQ ID NO: 1, CDR2 comprises a sequence sharing 50% or greater sequence identity with SEQ ID NO: 2 and CDR3 comprises a sequence sharing 50% or greater sequence identity with SEQ ID NO: 3.

Core Innovation

The invention provides polypeptides that include immunoglobulin heavy chain variable domains configured to bind interleukin-23 (IL-23) and tumor necrosis factor-alpha (TNF-alpha). The IL-23-binding domain and the TNF-alpha-binding domain are defined by complementarity determining regions CDR1, CDR2, and CDR3 specified by amino acid sequences set forth in SEQ ID NOs, with framework region designations and identity relationships relative to SEQ ID-defined embodiments.

The invention further provides a polypeptide comprising a first immunoglobulin heavy chain variable domain that binds to IL-23 and a second immunoglobulin heavy chain variable domain that binds to TNF-alpha, including formats with a protease-labile linker connecting the IL-23-binding and TNF-alpha-binding domains. The disclosure also includes multimer, bispecific, bihead format, homobihead, and heterobihead constructs, as well as conservative-substitution variants and explicit framework region-defined variants.

The document also includes an IL-23-binding polypeptide defined by the amino acid sequence of SEQ ID NO: 46. The documented disclosure further includes pharmaceutical composition and enteric coating contexts, nucleic acids, vectors, and host cells associated with expression of IL-23-binding and dual-binding constructs, with functional requirements described for IL-23 neutralization and protease resistance.

Claims Coverage

Two independent claims are provided, covering a dual-binding polypeptide with IL-23-binding and TNF-alpha-binding immunoglobulin heavy chain variable domains, and an IL-23-binding polypeptide defined by a specific amino acid sequence. The claim set further refines SEQ ID-specified CDRs, linker structure, sequence identity constraints, and therapeutic administration for autoimmune and/or inflammatory diseases.

Overall, the independent-claim coverage is built around IL-23-binding immunoglobulin variable-domain constructs, either combined with TNF-alpha binding in a single polypeptide with SEQ ID-specified CDRs or provided as a distinct IL-23-binding polypeptide with an SEQ ID-defined amino acid sequence.

Stated Advantages

Documented Applications