Interference No. 105,136 Paper 62
Wang v. Imler Page 11
the Ad genome....Substitution of the E1 or E4 regions produces
conditional recombinants which can be propagated in complementing cell
lines.
and that (Exh. 2012 at 40):
The creation of a human cell line (293) that contains and expresses most
of the E1a and E1b regions [citation omitted] has been invaluable both in
the genetic analysis of these regions and in the complementation of Ad
recombinants with heterologous sequences substituted for E1.
and that (Exh. 2012 at 46):
The Ad genome is large (- 36 kb) and current helper-independent vectors
have the capacity to accept up to approximately 7.5. kb of foreign DNA.
This results from the ability to package genomes of up to 106 mu (i.e., 38
kb) [and] from the availability of cell lines that express and thus
complement the E1 or E4 regions...
and that (Exh. 2012 at 46):
Another limitation [on the use of adenoviral vectors] is that wild-type (wt)
Ad infection ultimately kills the host cell, thereby limiting the time scale for
protein production.
43. Berkner II describes methods for generating adenovirus recombinants. (Exh.
2012 at 47-50).
44. Berkner II notes that "[f]oreign genes have...been inserted into the Ad genome
as part of a self-sufficient expression cassette that includes a promoter".
(Exh. 2012 at 47).
45. Berkner II does not specifically describe an adenovirus mutant having deletions
in both the E1 and E4 regions of the adenovirus genome.
46. Bridge II reports the construction and testing of mutant human type 5
adenoviruses having deletions in the E1b and E4 regions. (Exh. 2026, Fig. 1, at
11
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