Patent ID: 8114637

Claim:
A method for generating a batch of recombinant adenovirus having a deletion in the adenovirus' E1 region, the method comprising: a) introducing a recombinant adenovirus or recombinant adenovirus' genome into a cell comprising adenovirus E1 nucleic acid sequences able to complement the deletion of the adenovirus' E1 region of the recombinant adenovirus, wherein the cell comprises an adenovirus E1 A coding sequence, an adenovirus E1B-19K coding sequence, and an adenovirus E1B-55K coding sequence integrated into the cell's genome, wherein the cell has been prepared by a process comprising: introducing into a precursor cell a nucleic acid molecule or molecules selected from the group consisting of: i) a single nucleic acid molecule comprising the adenovirus E1 A coding sequence, the adenovirus E1B-19K coding sequence, and the adenovirus E1B-55K coding sequence, wherein the E1 A coding sequence and at least one of the E1B-19K and E1B-55K coding sequences are separated by at least 8 kb; and ii) two or more nucleic acid molecules together comprising the adenovirus E1 A, the adenovirus E1B-19K coding sequence and the adenovirus E1B-55K coding sequence, wherein the E1 A coding sequence and at least one of the E1B-19K and E1B-55K coding sequences are separated by at least 8 kb when the two or more nucleic acid molecules would form a single molecule by end-to-end joining before integrating into the precursor cell's genome; b) culturing the cell; and c) harvesting the batch of recombinant adenovirus.