Title:
ANTI-SENSE OLIGONUCLEOTIDES FOR ISOTYPE-SPECIFIC SUPPRESSION OF IMMUNOGLOBULIN PRODUCTION
Document Type and Number:
WIPO Patent Application WO/1993/010138
Kind Code:
A1
Abstract:
The invention includes oligonucleotides which are complementary to the 3'-end untranslated regions or to at least some of the splicing recognition region of an mRNA transcript precursor for a particular immunoglobulin heavy chain. More particularly, the oligonucleotides are complementary to at least a continuous 12 nucleotide segment of the sequence upstream to the 3' splice junction up to and including the branch point A residue. Sequences of some of the oligonucleotides of the invention are the underlined portions of SEQ ID NOS: 3-33. These oligonucleotides will hybridize with the splicing recognition region and prevent or inhibit maturation of the mRNA. This will prevent production of mRNA encoding a complete immunoglobulin, so that it will not be translated into a functional immunoglobulin. The invention also pertains to the preparation of these anti-sense oligonucleotides for specifically suppressing IgG and/or IgM production in patients suffering from autoimmune diseases and for specifically suppressing IgE in patients suffering from allergic diseases manifested by immediate-type hypersensitivities.
Inventors:
CHANG TSE WEN (US)
Application Number:
PCT/US1992/010024
Publication Date:
May 27, 1993
Filing Date:
November 18, 1992
Export Citation:
Assignee:
TANOX BIOSYSTEMS INC (US)
International Classes:
A61K45/00; C07H21/04; C12N15/113; (IPC1-7): A61K45/00; C07H21/00
Other References:
Molecular Biology, Vol. 24, No. 1, Part 2, August 1990 (Translation of January - February 1990), VLASOV et al., "Inhibition of Translation of Immunoglobulin mRNA in Vitro by Means of an Alkylating Derivative of an Oligonucleotide", pages 151-155, see entire document.
P.N.A.S. USA, Vol. 85, August 1988, GOODCHILD et al., "Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligonucleotides", pages 5507-5511, see entire document.
EMBO Journal, Vol. 7, No. 8, 1988, MUNROE, S.H., "Antisense RNA Inhibits Splicing of pre-mRNA in Vitro", pages 2523-2532, see entire document.
Journal of Allergy & Clinical Immunology, Vol. 17, No. 1, Part 2, Abstracts, No. 414, HALL et al., "Specific Inhibition of IgE Antibody Production in Vitro by an Antisense Oligonucleotide", page 243, Abstract only.
E.A. KABAT et al., "Sequences of Protein of Immunological Interest", Fourth edition, published 1987, cover sheet only.
See also references of EP 0641353A4
P.N.A.S. USA, Vol. 85, August 1988, GOODCHILD et al., "Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligonucleotides", pages 5507-5511, see entire document.
EMBO Journal, Vol. 7, No. 8, 1988, MUNROE, S.H., "Antisense RNA Inhibits Splicing of pre-mRNA in Vitro", pages 2523-2532, see entire document.
Journal of Allergy & Clinical Immunology, Vol. 17, No. 1, Part 2, Abstracts, No. 414, HALL et al., "Specific Inhibition of IgE Antibody Production in Vitro by an Antisense Oligonucleotide", page 243, Abstract only.
E.A. KABAT et al., "Sequences of Protein of Immunological Interest", Fourth edition, published 1987, cover sheet only.
See also references of EP 0641353A4
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