Interference 102,728
vector (M13), modifying the DNA-containing vector with an oligonucleotide primer which
lacks the codons encoding the glu-ala residues of the " factor spacer region, screening
the vectors with the oligonucleotide primer to isolate a clone having desired
modification, and sequencing said clone. These were all routine and predictable
procedures in genetic engineering.19 In addition, we find that the level of skill in the field
of molecular genetics at the relevant time was very high and that those having ordinary
skill in the art would have been able to use techniques then known in the art to make
Brake’s described n=0 construct. Thus, we find that the disclosure of the “n=0” DNA
construct in Brake 1, in combination with routine techniques and knowledge generally
available in the art, would have enabled those skilled in the art of genetic engineering to
make a species within the scope of Count 1 without undue experimentation at the time
the application was filed.
Dr. Tekamp-Olson describes a known alternative method for making a species
within the scope of the count which involves the use of the enzyme Bal 31 to remove
the sequence encoding the DPAP A (the glu-ala residues of the " factor spacer
sequence) site from a vector (pAB112) disclosed in Brake 1. Tekamp-Olson
Declaration, pp. 3-4, para. 5b; see also, para. 14 on p. 11, above. According to Dr.
Tekamp-Olson, this method of modifying DNA was known by those skilled in the art in
January, 1983. Id.
19 We point out that several of the techniques described by Dr. Tekamp-Olson;
viz., digestion of DNA with known restriction enzymes, subcloning into a vector,
screening with a synthetic oligonucleotide, are described on pp. 12-15 of Brake 1.
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