Modulation of cd40 expression

Abstract

Disclosed herein are antisense compounds and methods for decreasing CD40. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to CD40 include hyperproliferative disorders, graft versus host disease (GVHD), graft rejection, asthma, airway hyperresponsiveness, chronic obstructive pulmonary disease (COPD), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and certain forms of arthritis.

1 .- 46 . (canceled) 
     
     
         47 . A compound comprising a modified oligonucleotide consisting of 18 to 24 linked nucleosides having a nucleobase sequence comprising a portion of at least 18 contiguous nucleobases complementary to an equal length portion of nucleobases 8492 to 10547, 11244 to 12591 or 13802 to 14016 of SEQ ID NO: 4, wherein the nucleobase sequence of the modified oligonucleotide is at least 80% complementary to SEQ ID NO: 4. 
     
     
         48 . The compound of  claim 47 , wherein the nucleobase sequence of the compound is at least 85%, at least 90%, at least 95%, or 100% complementary to SEQ ID NO: 4. 
     
     
         49 . The compound of  claim 47 , wherein the modified oligonucleotide consists of 20 linked nucleosides. 
     
     
         50 . The compound of  claim 47 , wherein at least one internucleoside linkage is a modified internucleoside linkage. 
     
     
         51 . The compound of  claim 50 , wherein at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         52 . The compound of  claim 50 , wherein each modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         53 . The compound of  claim 47 , wherein the modified oligonucleotide comprises at least one modified sugar. 
     
     
         54 . The compound of  claim 53 , wherein at least one modified sugar is a bicyclic sugar. 
     
     
         55 . The compound of  claim 54 , wherein the bicyclic sugar has a 4′-CH(CH 3 )—O-2′ bridge or a 4′-(CH 2 ) n —O-2′ bridge, wherein n is 1 or 2. 
     
     
         56 . The compound of  claim 53 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl. 
     
     
         57 . The compound of  claim 47 , wherein at least one nucleoside comprises a modified nucleobase. 
     
     
         58 . The compound of  claim 57 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         59 . The compound of  claim 47 , wherein the modified oligonucleotide is single-stranded. 
     
     
         60 . The compound of  claim 47 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides;   a 3′ wing segment consisting of linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.   
     
     
         61 . The compound of  claim 60 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of ten linked deoxynucleosides;   a 5′ wing segment consisting of five linked nucleosides;   a 3′ wing segment consisting of five linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar, wherein at least one internucleoside linkage is a phosphorothioate linkage, and wherein each cytosine is a 5-methylcytosine.   
     
     
         62 . The compound of  claim 60 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of ten linked deoxynucleosides;   a 5′ wing segment consisting of three linked nucleosides;   a 3′ wing segment consisting of three linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a modified sugar, wherein at least one internucleoside linkage is a phosphorothioate linkage, and wherein each cytosine is a 5-methylcytosine.   
     
     
         63 . A composition comprising the compound of  claim 47 , or a salt thereof, and a pharmaceutically acceptable carrier or diluent. 
     
     
         64 . A method comprising administering to an animal the compound of  claim 47  for the treatment of cancer or an inflammatory or immune associated condition. 
     
     
         65 . The method of  claim 64 , wherein the animal is a human. 
     
     
         66 . The method of  claim 64 , wherein the administering is parenteral administration. 
     
     
         67 . The method of  claim 66 , wherein the parenteral administration is subcutaneous or intravenous administration. 
     
     
         68 . The method of  claim 64 , wherein the administering is aerosol, topical or oral administration.