Humanized anti-CD3 specific antibodies

• US 5,585,097 A
• Filed: 11/08/1993
• Issued: 12/17/1996
• Est. Priority Date: 03/24/1992
• Status: Expired due to Term

• Current Assignee: BTG International Limited (Boston Scientific Corporation)
• Original Assignee: British Technology Group Ltd.
• Inventors: Gorman, Scott D., Routledge, Edward G., Waldmann, Herman, Clark, Michael R., Bolt, Sarah L.
• Primary Examiner(s): Eisenschenk, Frank C.
• Application Number:
  US07/988,925
• Time in Patent Office: 1,135 Days
• Field of Search: 530/387.3, 530/388.75, 435/172.1, 435/172.3, 435/70.1, 435/71.1, 435/69.6, 435/240.1, 435/320.1, 424/133.1, 424/154.1, 536/23.53
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/74 Inducing cell proliferation

Abstract

Novel aglycosylated antibodies having a binding affinity for the CD3 antigen complex are of value for use in therapy, particularly in immunosuppression.

Claims

1. An aglycosylated IgG antibody which binds to the CD3 antigen complex, comprising:

a light chain having the sequence, reading in the leader-constant direction, of SEQ ID NO;

16, and

a heavy chain comprising a variable region having the sequence, reading in the leader-constant direction, of SEQ ID NO;

11 and an aglycosylated constant region derived from the wild type Glm (1,17) gene, wherein asparagine 297 is mutated to another amino acid.

2. A method of treating a patient to prevent renal allograft rejection, said method comprising the step of administering to said patient a therapeutically effective amount of an antibody according to claim 1.

3. An aglycosylated IgG antibody which binds to the CD3 antigen complex obtainable by co-transfecting subconfluent monolayers of dhfr-Chinese Hamster Ovary cells with vector p323 containing the heavy chain gene and vector p274 containing the re-shaped human λ

light chain.

4. A method of treating a patient to prevent renal allograft rejection, said method comprising the step of administering to said patient a therapeutically effective amount of an antibody according to claim 3.