Interference No. 105,136 Paper 62
Wang v. Imler Page 17
methods for generating Ad recombinants. (FF 43). 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". (FF 44). Berkner II does not specifically describe
an adenovirus mutant having deletions in both the E1 and E4 regions of the adenovirus
genome. (FF 45).
Bridge II describes adenovirus mutants having deletions in a portion of both the
E1b and E4 regions of the viral genome. (FF 46). At least one of these mutants, i.e.,
that mutant designated H5dl1016, is said to be defective for DNA replication. (FF 47).
H5dl1016 is said to have been propagated in the 293 cell line (FF 49), a cell line that
Berkner II describes as containing and expressing most of the E1a and E1b regions of
the Ad5 genome. (FF 42).
It would have been obvious to one having ordinary skill in the art at the time of
the invention to select an adenovirus mutant such as H5dl1016 to use as an expression
vector for heterologous genetic material. As noted in Berkner II, infection by wild type
adenovirus will ultimately kill the host cell. (FF 50). Thus, one skilled in the art would
have been motivated to use a mutant, such as H5dl1016, that is unable to replicate on
its own.
As the deletions present in H5dl1016 render the mutant replication defective, it
follows that H5dl1016 is defective for at least a portion of the functions of E1b and E4.
In particular, Bridge II states that "the joint disruption of the 116R and 496R proteins [in
H5dl1016] is important in conferring the defect in DNA replication". ( FF 48). It also
17
Page: Previous 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Next
Last modified: November 3, 2007