Adenovector pharmaceutical composition

Abstract

The present invention provides multiply deficient adenoviral vectors and complementing cell lines. Also provided are recombinants of the multiply deficient adenoviral vectors and a therapeutic method, particularly relating to gene therapy, vaccination, and the like, involving the use of such recombinants.

What is claimed is:  
     
         1 . An adenoviral vector that is deficient in two or more adenoviral gene functions.  
     
     
         2 . The adenoviral vector of  claim 1 , wherein at least one of the said two or more gene functions is selected from the group of gene functions comprising the E 1 , E 2 , E 3  and E 4  regions of the adenoviral genome.  
     
     
         3 . The adenoviral vector of  claim 1 , wherein at least one of the said two or more gene functions is selected from the group of gene functions comprising the late regions of the adenoviral genome.  
     
     
         4 . The adenoviral vector of  claim 2 , wherein at least one of the said two or more gene functions is selected from the group of gene functions comprising the late regions of the adenoviral genome.  
     
     
         5 . The adenoviral vector of  claim 1 , wherein the said two or more adenoviral gene functions is all the adenoviral gene functions.  
     
     
         6 . The adenoviral vector of  claim 5 , wherein said adenoviral vector comprises adenoviral inverted terminal repeats and one or more adenoviral promoters.  
     
     
         7 . The adenoviral vector of  claim 5 , wherein said adenoviral vector comprises adenoviral inverted terminal repeats and a packaging signal.  
     
     
         8 . The adenoviral vector of  claim 1 , wherein said adenoviral vector only functions in a complementing cell line.  
     
     
         9 . The adenoviral vector of  claim 8 , wherein said adenoviral vector only functions in a complementing cell line as a result of the modification of adnoviral inverted terminal repeats or packaging signal.  
     
     
         10 . A cell line that complements an adenoviral vector of  claim 1 .  
     
     
         11 . A cell line that complements an adenoviral vector of  claim 2 .  
     
     
         12 . A cell line that complements an adenoviral vector of  claim 3 .  
     
     
         13 . A cell line that complements an adenoviral vector of  claim 4 .  
     
     
         14 . A cell line that complements an adenoviral vector of  claim 5 .  
     
     
         15 . A cell line that complements an adenoviral vector of  claim 6 .  
     
     
         16 . A cell line that complements an adenoviral vector of  claim 7 .  
     
     
         17 . A cell line that complements an adenoviral vector of  claim 8 .  
     
     
         18 . A cell line that complements an adenoviral vector of  claim 9 .  
     
     
         19 . A cell line selected from the group consisting of those cell lines designated as 293/E4, 293/ORF-6, and 293/E4/E2A.  
     
     
         20 . A recombinant multiply deficient adenoviral vector of  claim 1  comprising a foreign gene.  
     
     
         21 . The recombinant vector of  claim 20 , wherein said foreign gene is the cystic fibrosis transmembrane regulator gene.  
     
     
         22 . The recombinant vector of  claim 20 , wherein said recombinant vector is selected from the group consisting of Ad GV . 10 , Ad GV . 11 , Ad GV . 12 , and Ad GV . 13 .  
     
     
         23 . The recombinant vector of  claim 22 , wherein said recombinant vector is selected from the group consisting of Ad GV CFTR. 10 , Ad GV CFTR. 11 , Ad GV CFTR. 12 , and Ad GV CFTR. 13 .  
     
     
         24 . A recombinant multiply deficient adenoviral vector of  claim 1  comprising a DNA sequence capable of expressing in a mammal a therapeutic agent.  
     
     
         25 . The recombinant multiply deficient adenoviral vector of  claim 24 , wherein said therapeutic agent is an antisense molecule selected from the group consisting of mRNA and a synthetic oligonucleotide.  
     
     
         26 . A recombinant multiply deficient adenoviral vector of  claim 1  comprising a DNA sequence capable of expressing in a mammal a polypeptide capable of eliciting an immune response to said polypeptide.  
     
     
         27 . A method of gene therapy comprising the administration to a patient in need of gene therapy a therapeutically effective amount of a recombinant multiply deficient adenoviral vector of  claim 20 .  
     
     
         28 . A method of gene therapy comprising the administration to a patient in need of gene therapy a therapeutically effective amount of a recombinant multiply deficient adenoviral vector of  claim 21 .  
     
     
         29 . A method of gene therapy comprising the administration to a patient in need of gene therapy a therapeutically effective amount of a recombinant multiply deficient adenoviral vector of  claim 22 .  
     
     
         30 . A method of gene therapy comprising the administration to a patient in need of gene therapy a therapeutically effective amount of a recombinant multiply deficient adenoviral vector of  claim 23 .  
     
     
         31 . The method of  claim 28 , wherein the recombinant multiply deficient adenoviral vector is administered to the lungs of said patient.  
     
     
         32 . The method of  claim 30 , wherein the recombinant multiply deficient adenoviral vector is administered to the lungs of said patient.  
     
     
         33 . A method of therapy comprising the administration to a patient in need of therapy a therapeutically effective amount of a recombinant multiply deficient adenoviral vector of  claim 1  comprising a DNA sequence capable of expressing a therapeutic agent.  
     
     
         34 . The method of  claim 33 , wherein said therapeutic agent is an antisense molecule selected from the group consisting of mRNA and a synthetic oligonucleotide.  
     
     
         35 . A method of vaccination comprising the administration to a patient in need of vaccination an immunity-inducing effective amount of a recombinant multiply deficient adenoviral vector of  claim 1  comprising a DNA sequence capable of expressing a polypeptide capable of eliciting an immune response to said polypeptide.