CTLA4-immunoglobulin fusion proteins having modified effector functions and uses therefor

US6750334B1 · kind B1 · utility

Assignee

• Repligen Corporation · US

Inventors

• Gary S. Gray · Brookline, US
• Jerry Carson · Belmont, US
• Kashi Javaherian · Heidelberg, DE
• Cindy L. Jellis · Londonderry, US
• Paul Rennert · Holliston, US
• Sandra Silver · Boston, US

Key dates

• Filing date: Feb 2, 1996
• Grant date: Jun 15, 2004
• Expiry date: Feb 9, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.