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Title:
PEMPHIGUS MONOCLONAL ANTIBODY
Document Type and Number:
WIPO Patent Application WO/2003/020769
Kind Code:
A1
Abstract:
It is intended to provide a monoclonal antibody having a pathological activity of inducing pemphigus lesions, a peptide useful as a remedy for pemphigus autoimmune disease which is specifically recognized by the above monoclonal antibody, etc. Antimouse Dsg3 antibody−producing cells occur in spleen cells of a pemphigus vulgaris model mouse constructed by using an autoantigen model mouse. Thus, spleen cells of the model mouse are fused with mouse myeloma cells with the use of polyethylene glycol to give hybridomas. Then monoclonal antibodies against Dsg3 are constructed and a monoclonal antibody having a pathological activity of inducing pemphigus lesions is screened therefrom. The base sequence and the amino acid sequence in its variable region (heavy and light chains) are determined and thus the specific epitope part is identified.

Inventors:
TSUNODA KAZUYUKI (JP)
AMAGAI MASAYUKI (JP)
NISHIKAWA TAKEJI (JP)
KOYASU SHIGEO (JP)
Application Number:
PCT/JP2002/008987
Publication Date:
March 13, 2003
Filing Date:
September 04, 2002
Export Citation:
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Assignee:
UNIV KEIO (JP)
TSUNODA KAZUYUKI (JP)
AMAGAI MASAYUKI (JP)
NISHIKAWA TAKEJI (JP)
KOYASU SHIGEO (JP)
International Classes:
A61K38/17; A61P31/12; A61P37/02; A61P43/00; C07K16/18; C07K16/28; C12N5/20; C12N15/13; G01N33/564; (IPC1-7): C07K16/28; C07K14/47; C12N5/20; A01K67/027; A61K38/16; A61P31/12; A61P37/02; A61P43/00; G01N33/564
Foreign References:
JPH08188540A1996-07-23
Other References:
TSUNODA K. ET AL.: "Development of anti-desmoglein 2 (Dsg3) pathogenic monoclonal antibody using active disease mouse model for pemphigus vulgaris (PV)", J. INVEST. DERMATOL., vol. 117, no. 2, August 2001 (2001-08-01), pages 394, XP002961049
TSUNODA K. ET AL.: "Production of anti-desmoglein 3 mouse monoclonal antibodies using active disease mouse model for pemphigus", J. INVEST. DERMATOL., vol. 114, no. 4, 2000, pages 846, XP002904796
AMAGAI M. ET AL.: "Use of autoantigen-knockout mice in developing an active autoimmune disease model for pemphigus", J. CLIN. INVEST., vol. 105, no. 5, 2000, pages 625 - 631, XP002946608
AMAGAI M. ET AL.: "Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice", J. CLIN. INVEST., vol. 102, no. 4, 1998, pages 775 - 782, XP002904797
AMAGAI M. ET AL.: "Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion", CELL, vol. 67, no. 5, 1991, pages 869 - 877, XP002904798
TSUNODA K. ET AL.: "A pathogenic antidesmoglein 3 monoclonal antibody recognizes the N-terminal adhesive region of desmoglein 3", J. INVEST. DERMATOL., vol. 119, no. 1, July 2002 (2002-07-01), pages 228, XP002904799
OHYAMA M. ET AL.: "Immunologic and histopathologic characterization of active disease model mouse for pemphigus vulgaris", J. INVEST. DERMATOL., vol. 117, no. 2, August 2001 (2001-08-01), pages 459, XP002904800
ISHIKAWA H. ET AL.: "Molecular cloning of the mouse desmoglein 3 gene (Dsg3): genomic structure and homology with the human gene", J. INVEST. DERMATOL., vol. 106, no. 4, 1996, pages 848, XP002983501
FUTEI Y. ET AL.: "Use of domain-swapped molecules for conformational epitope mapping of desmoglein 3 in pemphigus vulgaris", J. INVEST. DERMATOL., vol. 115, no. 5, 2000, pages 829 - 834, XP002983502
Attorney, Agent or Firm:
Hirota, Masanori (8-5 Akasaka 2-chom, Minato-ku Tokyo, JP)
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