Patent NL-1027975-C2 (NL)
Title: New antibody to Mucosal Adressin Cell Adhesion Molecule, useful for diagnosing and treating an inflammatory disease, e.g. inflammatory bowel disease, ulcerative colitis, gastritis, insulin-dependent diabetes or graft versus host disease
Inventor: PULLEN NICOLAS
IPC: C12N5/06
Filed: 2005-01-07
Granted: 2005-12-23
Abstract: A human monoclonal antibody or its antigen-binding portion that specifically binds to Mucosal Adressin Cell Adhesion Molecule (MAdCAM), is new. A human monoclonal antibody or its antigen-binding portion, produced by a hybridoma cell line, that specifically binds to Mucosal Adressin Cell Adhesion Molecule (MAdCAM), where the antibody is selected from an antibody comprising any of the 17 sequences of 233-241 amino acids (SEQ ID NOS: 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 54, 58, 62, 66 or 68), without the signal sequences, where the heavy chain of the antibody or its portion comprises the heavy chain CDR1, CDR2 and CDR3 amino acid sequences of a reference monoclonal antibody and/or where the light chain comprises the light chain CDR1, CDR2 and CDR3 amino acid sequences of a reference monoclonal antibody, where the antibody or its portion comprises one or more of an FR1, FR2, FR3 or FR4 amino acid sequence of a human monoclonal antibody, where the reference or human monoclonal antibody is selected from 1.7.2, 1.8.2, 6.14.2, 6.22.2, 6.34.2, 6.67.1, 6.73.2, 6.77.1, 7.16.6, 7.20.5, 7.26.4, 9.8.2, 6.22.2-mod, 6.34.2-mod, 6.67.1-mod, 6.77.1-mod and 7.26.4-mod. Independent claims are also included for: (1) a hybridoma cell line that produces the human monoclonal; (2) a pharmaceutical composition comprising an amount of the monoclonal antibody or its antigen-binding portion and a pharmaceutical carrier; (3) treating inflammatory disease in a subject; (4) an isolated cell line that produces the monoclonal antibody or its antigen-binding portion or the heavy chain or light chain of the antibody or of its portion; (5) an isolated nucleic acid molecule comprising a nucleotide sequence encoding the heavy chain or its antigen-binding portion or the light chain or its antigen-binding portion of an antibody described above; (6) a vector comprising the nucleic acid molecule, where the vector optionally comprises an expression control sequence operably linked to the nucleic acid molecule; (7) a host cell comprising the vector or the nucleic acid molecule above; (8) producing a human monoclonal antibody or its antigen-binding portion that specifically binds MAdCAM; (9) a non-human transgenic animal or transgenic plant comprising: (i) nucleic acid molecule encoding the heavy chain or its antigen-binding portion, (ii) a nucleic acid molecule encoding the light chain or its antigen-binding portion, or both (i) and (ii) of an antibody, where the non-human transgenic animal or transgenic plant expresses the heavy chain and/or light chain; (10) isolating an antibody or its antigen-binding portion that specifically binds to MAdCAM; (11) treating a subject in need with a human antibody or its antigen-binding portion that specifically binds to MAdCAM and inhibits binding to alpha 4beta 7; (12) inhibiting alpha 4beta 7 binding to cells expressing human MAdCAM; (13) inhibiting MAdCAM-mediated leukocyte-endothelial cell adhesion; (14) inhibiting MAdCAM-mediated leukocyte adhesion, migration and infiltration into tissues; (15) inhibiting alpha 4beta 7/MAdCAM-dependent cellular adhesion; (16) inhibiting the MAdCAM-mediated recruitment of lymphocytes to gastrointestinal lymphoid tissue; (17) diagnosing a disorder characterized by circulating soluble human MAdCAM; (18) detecting inflammation in a subject; (19) a diagnostic kit comprising the monoclonal antibody or its antigen-binding portion; (20) a vaccine comprising an amount of the human antibody or its antigen-binding portion and a pharmaceutical carrier; and (21) detecting the effect of administration of an inhibitory anti-MAdCAM antibody or its antigen-binding portion to a subject. ACTIVITY : Antiinflammatory; Gastrointestinal-Gen; Antiulcer; Hepatotropic; Antidiabetic; Immunosuppressive. No biological data given. MECHANISM OF ACTION : Gene Therapy; Vaccine.