Compound with affinity for the cytotoxic T...

Details Compound with affinity for the cytotoxic T... Compound with affinity for the cytotoxic T...

2011-02-22

2011-02-22

Rawlings, Stephen L (Department: 1643)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C530S350000, C536S023500

Reexamination Certificate

active

07892827

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 KDof 50 nM or less. The invention also relates to a pharmaceutical composition comprising such a compound or mutein as well as to various pharmaceutical uses of such a compound or mutein, for example, for the prevention and/or treatment of cancer, an auto-immune disease or an infectious disease.

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Beste et al., “Small antibody-like proteins with prescribed ligand specificities derived from the lipocalin fold,” PNAS, Mar. 1999, 96:1898-1903.
Skerra et al., “‘Anticalins’: a new class of engineered ligand-binding proteins with antibody-like properties,” Reviews in Molecular Biotechnology, 2001, 74:257-275.

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