IL-23 antibody compositions and methods of use

Inventors

Kwan, Byron Hua • Shaheen, Hussam Hisham

Assignees

Paragon Therapeutics Inc

Abstract

Provided herein are interleukin 23 (IL-23) binding proteins (e.g., antibodies) and methods of use.

Core Innovation

The invention provides an interleukin 23 (IL-23) binding protein comprising a heavy chain variable domain (VH) comprising the amino acid sequence of SEQ ID NO: 145 and a light chain variable domain (VL) comprising the amino acid sequence of SEQ ID NO: 146. In some embodiments, the invention defines alternative VH and VL amino acid sequences using SEQ ID NO: 143 and SEQ ID NO: 144. The disclosed binding proteins are described as inhibiting IL-23-driven signaling and IL-23-induced cytokine release in functional comparisons.

The invention further describes IL-23 binding proteins that include a modified human IgG Fc region. The Fc region is described with half-life extending and/or effector-function altering substitutions, including named EU-numbered amino-acid substitutions and an Fc chain having the amino acid sequence of SEQ ID NO: 15. Exemplary functional comparisons are described by inhibition of IL-23-driven STAT3 activation and inhibition of IL-23-induced IL-17 release, including relative IC50 comparisons versus a reference antibody.

The invention also discloses nucleic acids encoding the IL-23 binding protein with the same defined VH and VL sequences, together with expression vectors and host cells comprising such nucleic acids or expression vectors. The disclosed therapeutic use is directed to inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, and to other inflammatory conditions described in the document. The disclosed therapeutic context includes pharmaceutical compositions with a pharmaceutically acceptable carrier and may include co-administration with a second therapeutic agent.

Claims Coverage

Two independent claims are identified, covering an IL-23 binding protein defined by specific VH/VL sequences and an isolated nucleic acid encoding that IL-23 binding protein. The independent claims focus on a defined heavy-chain variable domain and light-chain variable domain sequence set (SEQ ID NO: 145 and SEQ ID NO: 146), with additional inventive coverage in dependent claims relating to Fc format/modification and nucleic acid/expression system formats.

Across the independent claims, the main inventive focus is a specific IL-23 binding protein defined by VH (SEQ ID NO: 145) and VL (SEQ ID NO: 146). Dependent claim coverage further specifies nucleic-acid and protein formats, including Fc region composition and defined Fc chain sequence (SEQ ID NO: 15), and optional alternative variable-domain sequence options (SEQ ID NO: 143/144).

Stated Advantages

Documented Applications