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. 26Page: Previous 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 NextLast modified: November 3, 2007