Compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4)

US7892827B2 · kind B2 · utility

Assignee

• Pieris AG · DE

Inventors

• Gabriele Matschiner · Munich, DE
• Andreas Hohlbaum · Paunzhausen, DE
• Steffen Schlehuber · Ruppertsberg, DE
• Martin Pöhlchen · Haar, DE
• Arne Skerra · Freising, DE

Key dates

• Filing date: Nov 25, 2005
• Grant date: Feb 22, 2011
• Expiry date: Nov 10, 2026

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P37/06
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention relates to a compound with affinity for the cytotoxic T lymphocyte-associated antigen (CTLA-4), wherein the compound exhibits a synergistic mode of action in that the compound: (a) increases T cell priming or T cell expansion or the generation of memory T cells by blocking of CTLA-4, and (b) enhances effector T cell activity in tumor tissue or lymphoid tissue by blocking of CTLA-4. The compound of the invention can be a protein, a small organic molecule, a peptide, or a nucleic acid. The invention also relates to a mutein derived from a protein selected from the group consisting of human neutrophil gelatinase-associated lipocalin (hNGAL), rat α2-microglobulin-related protein (A2m) and mouse 24p3/uterocalin (24p3), said mutein having binding specificity for the cytotoxic T lymphocyte-associated antigen (CTLA-4), wherein said mutein: (a) comprises amino acid replacements at least one of the sequence position corresponding to sequence positions 33 to 54, 66 to 83, 94 to 106, and 123 to 136 of hNGAL, and (b) binds human CTLA-4 with a KD of 50 nM or less. The invention also relates to a pharmaceutical composition comprising such a compound or mutein as well as to v…