Appeal No. 1997-2139
Application No. 08/114,595
OPINION
1. Rejection of claim 49 under § 103 over Muzyczka and Drumm
Muzyczka reviews the biology of adeno-associated virus (AAV) and its use as a
general transduction vector for mammalian cells. According to Muzyczka, AAV is a
human virus which, except under special circumstances, requires coinfection with a
helper virus, e.g., a herpes or adeno virus, to replicate. In the absence of a helper
virus, AAV establishes a latent infection in which its chromosome is integrated into the
host chromosome. (§ 1, pp. 97-98; Fig. 1). The first use of AAV as a viral transduction
vector comprised replacing the AAV capsid gene with nonviral DNA (i.e., bacterial
neomycin resistance gene under control of the SV40 early promoter) to produce a
recombinant plasmid which was then transfected into human cells that had been
infected with adenovirus. The cells were cotransfected with a second plasmid, itself
defective for packaging but containing a wild type capsid gene, to supply the missing
capsid protein. The resulting virus stock contained both adenovirus and AAV
recombinant virus. Adenovirus was inactivated by heat or removed by density gradient
centrifugation. (§ 4, pp. 110-112; Fig. 6). According to Muzyczka, rep- AAV vectors are
attractive candidates for human gene therapy because (1) the cloning capacity of 5 kb
can accommodate a variety of cDNAs, (2) the transduction frequency in human cells is
high, (3) no disease has been associated with AAV in either human or animal
populations, (4) AAV proviruses appear to be stable, and (5) in the absence of the rep
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