US2006188479A1PendingUtilityA1

Adenovirus vectors containing cell status-specific response elements and methods of use thereof

67
Individually held — no corporate assignee on recordPriority: Sep 10, 1998Filed: Aug 18, 2005Published: Aug 24, 2006
Est. expirySep 10, 2018(expired)· nominal 20-yr term from priority
Inventors:De-Chao YuDaniel R. Henderson
A61K 35/13A61K 48/0058C12N 2830/008C12N 2710/10343C12N 15/86C12N 2710/10345C12N 2830/002A61P 35/00C12N 2830/007
67
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Claims

Abstract

The present invention provides adenoviral vectors comprising cell status-specific transcriptional regulatory elements which confer cell status-specific transcriptional regulation on an adenoviral gene. A “cell status” is generally a reversible physiological and/or environmental state. The invention further provides compositions and host cells comprising the vectors, as well as methods of using the vectors.

Claims

exact text as granted — not AI-modified
1 - 28 . (canceled)  
     
     
         29 . A replication-competent adenovirus vector for selective cytolysis of a target cell with a disrupted RB function, comprising: 
 an E2F-1 transcriptional regulatory element (TRE) operably linked to an adenovirus gene essential for replication selected from the group consisting of E1A, E1B and E4 and a transgene or a gene that contributes to cytotoxicity or cell death, wherein said vector effects selective cytolysis due to selective replication in a target cell with disrupted RB function.    
     
     
         30 . The adenovirus vector of  claim 29 , wherein said E2F-1 TRE is human.  
     
     
         31 . The adenovirus vector of  claim 30 , wherein said E2F-1 TRE comprises the nucleotide sequence set forth in SEQ ID NO:2.  
     
     
         32 . The adenovirus vector of  claim 31 , wherein said E2F-1 TRE comprises a nucleotide sequence having at least 80% sequence identity with the sequence set forth in SEQ ID NO:2.  
     
     
         33 . The adenovirus vector of  claim 29 , wherein said transgene is operably linked to a cell-type specific transcriptional regulatory element (TRE).  
     
     
         34 . The adenovirus vector of  claim 33 , wherein said cell-type specific transcriptional regulatory element (TRE) is a tumor cell-specific transcriptional regulatory element (TRE).  
     
     
         35 . The adenovirus vector of  claim 34 , wherein said tumor cell-specific transcriptional regulatory element (TRE) is selected from the group consisting of a prostate-specific TRE (PSA-TRE), a glandular kallikrein-1 TRE (hKLK2-TRE), a probasin TRE (PB-TRE), an α-fetoprotein TRE (AFP TRE) and a carcinoembryonic antigen TRE (CEA TRE).  
     
     
         36 . The adenovirus vector of  claim 29 , wherein said transgene is a cytokine.  
     
     
         37 . The adenovirus vector of  claim 36 , wherein said cytokine is GM-CSF.  
     
     
         38 . The adenovirus vector of  claim 29 , wherein said gene that contributes to cytotoxicity or cell death is ADP.  
     
     
         39 . The adenovirus vector of  claim 38 , wherein said ADP gene has a sequence presented as SEQ ID NO:5.  
     
     
         40 . The adenoviral vector of  claim 29 , further comprising a deletion in the E3 region.  
     
     
         41 . A composition comprising a replication competent adenovirus vector of  claim 29  and a pharmaceutically acceptable excipient.  
     
     
         42 . A composition comprising a replication competent adenovirus vector of  claim 37  and a pharmaceutically acceptable excipient.  
     
     
         43 . A viral vector particle comprising the adenovirus vector of  claim 29 .  
     
     
         44 . A viral vector particle comprising the adenovirus vector of  claim 37 .  
     
     
         45 . An isolated host cell comprising the adenovirus vector of  claim 29 .  
     
     
         46 . An isolated host cell comprising the adenovirus vector of  claim 37 .  
     
     
         47 . A eukaryotic cell transfected with the viral vector particle of  claim 29 .  
     
     
         48 . A eukaryotic cell transfected with the viral vector particle of  claim 37 .  
     
     
         49 . A replication-competent adenovirus vector for selective cytolysis of a target cell, comprising: 
 a cell status-specific transcriptional regulatory element (TRE) selected from a cell cycle-activated TRE or cell-cycle specific TRE, operably linked to an adenovirus gene essential for replication selected from the group consisting of E1A, E1B and E4, wherein said vector effects selective cytolysis of said target cell.    
     
     
         50 . The adenovirus vector of  claim 49 , wherein said target cell exhibits de-regulated cell division.  
     
     
         51 . The adenovirus vector of  claim 49 , wherein said target cell is in S phase.  
     
     
         52 . The adenovirus vector of  claim 49 , wherein said cell cycle-activated TRE or cell-cycle specific TRE is an hTERT TRE.  
     
     
         53 . The adenovirus vector of  claim 52 , further comprising a transgene or a gene that contributes to cytotoxicity or cell death.  
     
     
         54 . The adenovirus vector of  claim 53 , wherein said transgene is operably linked to a cell-type specific transcriptional regulatory element (TRE).  
     
     
         55 . The adenovirus vector of  claim 54 , wherein said cell-type specific transcriptional regulatory element (TRE) is a tumor cell-specific transcriptional regulatory element (TRE).  
     
     
         56 . The adenovirus vector of  claim 55 , wherein said tumor cell-specific transcriptional regulatory element (TRE) is selected from the group consisting of a prostate-specific TRE (PSA-TRE), a glandular kallikrein-1 TRE (hKLK2-TRE), a probasin TRE (PB-TRE), an α-fetoprotein TRE (AFP TRE) and a carcinoembryonic antigen TRE (CEA TRE).  
     
     
         56 . The adenovirus vector of  claim 53 , wherein said transgene is a cytokine.  
     
     
         57 . The adenovirus vector of  claim 57 , wherein said cytokine is GM-CSF.  
     
     
         58 . The adenovirus vector of  claim 53 , wherein said gene that contributes to cytotoxicity or cell death is ADP.  
     
     
         59 . The adenovirus vector of  claim 59 , wherein said ADP gene has a sequence presented as SEQ ID NO:5.  
     
     
         60 . The adenoviral vector of  claim 49 , further comprising a deletion in the E3 region.  
     
     
         61 . A composition comprising a replication competent adenovirus vector of  claim 52  and a pharmaceutically acceptable excipient.  
     
     
         62 . A viral vector particle comprising the adenovirus vector of  claim 52 .  
     
     
         63 . An isolated host cell comprising the adenovirus vector of  claim 52 .  
     
     
         64 . A eukaryotic cell transfected with the viral vector particle of  claim 63.

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