Anti IL-6 domain antibodies with fatty acid substituents

Inventors

Egebjerg, Thomas • Bjelke, Jais Rose • Yang, Che • Reedtz-Runge, Steffen • Kopp, Katharina Luise Maria • Balantic-Nielsen, Emma • SASSENE, PHILIP JONAS

Assignees

Novo Nordisk AS

Abstract

The present invention relates to compounds (e.g. ISVDs, polypeptides, polypeptide derivatives) capable of binding to Interleukin-6 (IL-6) and their use in the treatment of inflammatory diseases such as, e.g. cardiovascular disease (CVD).

Core Innovation

The invention relates to a polypeptide derivative capable of binding IL-6. The polypeptide derivative comprises a VHH or VH domain having complementarity-determining regions CDR1 EYAVG, CDR2 DIGEQAENTWYAESVLG, and CDR3 DKYGVGGNAQGYYDS according to the Kabat definition, and an extension attached to the C-terminal end of the VHH or VH domain.

The extension comprises an amino acid sequence set out in SEQ ID NO: 72, with cysteines at defined positions. A first substituent is attached to the cysteine in position 4 of SEQ ID NO: 72, and a second substituent is attached to the cysteine in position 6 of SEQ ID NO: 72. Each of the first substituent and the second substituent comprises a specified structure, including Chem. 24-based substituent structures and related variants referenced in the document.

The disclosure further describes IL-6 binding immunoglobulin single variable domain constructs fused to a C-terminal extension, including SEQ ID NO: 72 or SEQ ID NO: 78, and mentions preferred humanisation, molecular weight and pI ranges, lipid/half-life extending moieties, pharmaceutical compositions with pharmaceutically acceptable carriers, SNAC and nicotinamide, and reported binding and functional assays and pharmacokinetic and pharmacodynamic measurements using biomarker readouts such as serum amyloid A1 (SAA1).

Claims Coverage

The claim coverage centers on one independent claim directed to an IL-6 binding polypeptide derivative with defined CDR sequences, a C-terminal extension, and two substituents attached at specific cysteine positions. Dependent claims add a molecular weight constraint, pharmaceutical composition components, and treatment methods for inflammatory disease and ASCVD.

Overall, the claim coverage is anchored on an IL-6 binding polypeptide derivative defined by specific VHH or VH CDR sequences, a C-terminal extension defined by SEQ ID NO: 72, and two substituents attached at cysteine positions 4 and 6 of the extension. Dependent refinements add a molecular weight range, SNAC and nicotinamide, and treatment methods for inflammatory disease and ASCVD.

Stated Advantages

Documented Applications