Immunosuppression compound and treatment method
First Claim
1. A composition for suppressing an immune response in a subject, comprising(a) a pharmaceutically effective amount of a morpholino antisense oligonucleotide having between 12 and 40 morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′
- -exocyclic carbon of an adjacent subunit and having a targeting sequence that contains at least 12 contiguous bases that are complementary to SEQ ID NO;
22, the region of SEQ ID NO;
1 targeted by the overlapping sequences identified by SEQ ID NOS;
4-6, where the oligonucleotide is capable of forming with pre-processed cytotoxic T-lymphocyte antigen-4 (CTLA-4) mRNA, a heteroduplex structure characterized by a Tm of dissociation of at least 45°
C.; and
(b) a pharmaceutically acceptable carrier.
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Accused Products
Abstract
Provided are methods and antisense oligonucleotide analogs for suppressing an immune response in a mammalian subject, for the treatment or prevention of an autoimmune condition or transplantation rejection. The oligonucleotide analogs provided herein comprise a targeting sequence complementary to a preprocessed CTLA-4 mRNA region that spans the splice junction between intron 1 and exon 2 of the preprocessed CTLA-4 mRNA. Also provided are methods of use, in which the oligonucleotides are effective, when administered to a subject, to form within host cells, a heteroduplex structure (i) composed of the preprocessed CTLA-4 mRNA and the oligonucleotide compound, (ii) characterized by a Tm of dissociation of at least 45° C., and (iii) resulting in an increased ratio of processed mRNA encoding ligand-independent CTLA-4 to processed mRNA encoding full-length CTLA-4.
84 Citations
16 Claims
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1. A composition for suppressing an immune response in a subject, comprising
(a) a pharmaceutically effective amount of a morpholino antisense oligonucleotide having between 12 and 40 morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ - -exocyclic carbon of an adjacent subunit and having a targeting sequence that contains at least 12 contiguous bases that are complementary to SEQ ID NO;
22, the region of SEQ ID NO;
1 targeted by the overlapping sequences identified by SEQ ID NOS;
4-6, where the oligonucleotide is capable of forming with pre-processed cytotoxic T-lymphocyte antigen-4 (CTLA-4) mRNA, a heteroduplex structure characterized by a Tm of dissociation of at least 45°
C.; and(b) a pharmaceutically acceptable carrier. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)
- -exocyclic carbon of an adjacent subunit and having a targeting sequence that contains at least 12 contiguous bases that are complementary to SEQ ID NO;
Specification