Recombinant adenoviral vector and methods of use

• US 6,989,268 B2
• Filed: 05/19/2003
• Issued: 01/24/2006
• Est. Priority Date: 10/25/1993
• Status: Expired due to Fees

• Current Assignee: Canji Inc. (Merck & Co., Inc.)
• Original Assignee: Canji Inc. (Merck & Co., Inc.)
• Inventors: Maneval, Daniel C., Wills, Ken N., Gregory, Richard J.
• Primary Examiner(s): Guzo, David
• Application Number:
  US10/441,510
• Publication Number:
  US 20040038404A1
• Time in Patent Office: 981 Days
• Field of Search: 435/320.1, 435/325, 435/366, 424/93.1, 424/93.2, 424/93.6
• US Class Current: 435/320.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/4746 p53
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination
• CPC Class Codes: C12N 2830/85 mammalian
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with thymidine kinase metabolite in order to be effective).

Claims

1. A recombinant adenovirus expression vector comprising

a partial or total deletion of a protein IX DNA sequence;

and

a DNA sequence encoding p21.

2. The recombinant adenovirus expression vector of claim 1, wherein the protein IX polyadenylation site is deleted from the adenovirus expression vector.

3. The recombinant adenovirus expression vector of claim 1, wherein said adenovirus is a group C adenovirus selected from a serotype 1, 2, 5, or 6.

4. The recombinant adenovirus expression vector of claim 1, wherein said DNA sequence encoding p21 is operably linked to a cytomegalovirus (CMV) promoter.

5. The recombinant adenovirus expression vector of claim 1, wherein said DNA sequence encoding p21 further comprises a palyadenylation site.

6. A host cell transformed with the recombinant adenovirus expression vector of claim 1.

7. A composition comprising the recombinant adenovirus expression vector of claim 1 and a pharmaceutically acceptable carrier.

8. The composition of claim 7, wherein said DNA sequence encoding p21 is operably linked to a cytomegalovirus (CMV) promoter.

9. The composition of claim 7, wherein said pharmaceutically acceptable carrier comprises a physiologically acceptable compound.