Title:
ANTI-HLA-DQ2.5/8 ANTIBODY AND ITS USE FOR THE TREATMENT OF CELIAC DISEASE
Document Type and Number:
WIPO Patent Application WO/2018/155692
Kind Code:
A1
Abstract:
The invention provides anti-HLA-DQ2.5/8 antibodies and methods of using the same. The antibodies of the present invention have binding activity to human HLA-DQ2.5/8 and monkey MHC-DQ, but substantially no binding activity to HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5/8. The antibodies bind to HLA-DQ2.5/8 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5/8 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5/8 and TCR, and thus block the interaction between HLA-DQ2.5/8 and an HLA-DQ2.5/8-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain. These characteristics are particularly useful for treating celiac disease. Thus, the present invention also provides a method of treating celiac disease using the antibodies of the present invention.
Inventors:
OKURA YUU (SG)
TAKAHASHI NORIYUKI (SG)
TAKAHASHI NORIYUKI (SG)
Application Number:
PCT/JP2018/007023
Publication Date:
August 30, 2018
Filing Date:
February 26, 2018
Export Citation:
Assignee:
CHUGAI PHARMACEUTICAL CO LTD (JP)
International Classes:
C07K16/28; A61K39/395; A61P1/00; A61P37/06; G01N33/531; G01N33/577; C12N15/13; C12P21/08
Domestic Patent References:
| WO2010141658A1 | 2010-12-09 | |||
| WO2002083722A2 | 2002-10-24 |
Other References:
MEGIORNI, FRANCE SCA ET AL.: "Celiac disease predisposition: practical implications of the HLA molecular typing", JOURNAL OF BIOMEDICAL SCIENCE, vol. 19, no. 88, 2012, pages 1 - 5, XP021106563
M. FLEUR DU PRE ET AL.: "Tolerance to Ingested Deamidated Gliadin in Mice is Maintained by Splenic , Type 1 Regulatory T cells", GASTROENTEROLOGY, vol. 141, no. 2, August 2011 (2011-08-01), pages 610 - 662, XP028253746, Retrieved from the Internet
MOLDENHAUER, G ET AL.: "Surface-expressed invariant chain ( CD 74) is required for internalization of human leucocyte antigen-DR molecules to early endosomal compartments", IMMUNOLOGY, vol. 96, no. 3, 1 March 1999 (1999-03-01), pages 473 - 484, XP055590649, ISSN: 0019-2805, DOI: 10.1046/j.1365-2567.1999.00676.x
STEIN , RHONA ET AL.: "CD 74: A New Candidate Target for the Immunotherapy of B- cell Neoplasms", CLIN CANCER RES, vol. 13, no. 18, 15 September 2007 (2007-09-15), pages 5556s - 5563s, XP002510850, Retrieved from the Internet
See also references of EP 3585818A4
M. FLEUR DU PRE ET AL.: "Tolerance to Ingested Deamidated Gliadin in Mice is Maintained by Splenic , Type 1 Regulatory T cells", GASTROENTEROLOGY, vol. 141, no. 2, August 2011 (2011-08-01), pages 610 - 662, XP028253746, Retrieved from the Internet
MOLDENHAUER, G ET AL.: "Surface-expressed invariant chain ( CD 74) is required for internalization of human leucocyte antigen-DR molecules to early endosomal compartments", IMMUNOLOGY, vol. 96, no. 3, 1 March 1999 (1999-03-01), pages 473 - 484, XP055590649, ISSN: 0019-2805, DOI: 10.1046/j.1365-2567.1999.00676.x
STEIN , RHONA ET AL.: "CD 74: A New Candidate Target for the Immunotherapy of B- cell Neoplasms", CLIN CANCER RES, vol. 13, no. 18, 15 September 2007 (2007-09-15), pages 5556s - 5563s, XP002510850, Retrieved from the Internet
See also references of EP 3585818A4
Attorney, Agent or Firm:
HARUNA, Masao et al. (JP)
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