CTLA4 Ig fusion proteins

• US 5,844,095 A
• Filed: 01/18/1995
• Issued: 12/01/1998
• Est. Priority Date: 06/27/1991
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Ledbetter, Jeffrey A., Linsley, Peter S., Brady, William, Damle, Nitin K.
• Primary Examiner(s): Ulm, John
• Assistant Examiner(s): Spector, Lorraine
• Application Number:
  US08/375,390
• Time in Patent Office: 1,413 Days
• Field of Search: 435/69.7, 530/386, 530/387.1, 530/387.3, 536/23.1, 536/23.5, 935/10, 514/2, 424/85.8, 424/134.1, 424/192.1
• US Class Current: 530/387.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Claims

1. A CTLA4Ig fusion protein which binds the B7 antigen, said protein having a first amino acid sequence consisting of the extracellular domain of CTLA4 and a second amino acid sequence consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin molecule.

2. A CTLA4Ig fusion protein which bonds the B7 antigen, said protein having (a) a first amino acid sequence beginning with alanine at amino acid position 1 and ending with aspartic acid at amino acid position 125 of SEQ ID NO 13 which represents the extracellular domain of CTLA4 and (b) a second amino acid sequence consisting of the hinge, CH2 and CH3 regions of a human immunoglobulin molecule.