Interference 102,728
Second, Brake points out the loop deletion method described in the September,
1983, Genentech paper (SX 53) mandates the use of two (2) unique oligonucleotide
primers.39 Paper No. 190, p. 52. An additional primer (the “LAC” primer), which is
complementary to a region upstream from the site of mutagenesis, is also required. Id.,
SX 53, Bates No. 708, col. 2, last paragraph and Figure 3. Although it is an essential
reagent for the “loop deletion” procedure, Singh does not point to any evidence which
indicates that Dr. Singh ordered or possessed the LAC primer on December 1, 1982, or
understood the need to order or possess said primer prior to January 12, 1983.
which is a photocopy of the original “pink” file copy. Written on it, in the top right
hand corner, is a note in Mr. Ng’s handwriting, which I recognize, which states as
follows: “legal got original, Peter 2/27/92.” That particular form has been
maintained in our possession as a part of these files since that date. The
original pink copy was maintained in our possession from the date of the request
until 2/27/92. Copies of the original “pink” copies and one photocopy are shown
and Singh Exhibit 54, Bates No. 000714-000719.
Thus, we find that Mr. Vasser does not mention the loop deletion mutagenesis
technique, let alone testify as to his awareness that Dr. Singh intended to employ the
24-mer to make a compound within the scope of the count using said technique.
39 Brake directs attention to the teachings of the Genentech article which
describes the differences between the new loop deletion procedure and prior
mutagenesis techniques. Paper No. 190, pp. 58-59. The teachings are, in relevant
part:
Similar in vitro mutagenesis protocols involving a single primer ... have
been used by others. In such a single primer approach, heteroduplex
structures are stabilized by eventually joining the 3' end of the in vitro-
synthesized DNA to its own 5' end after synthesis of one full-length
complement of the template DNA. To obtain heteroduplex stability after
short times of DNA synthesis, we used an additional primer (“LAC”)
complementary to a region upstream from the site of mutagenesis [SX 53,
Bates No. 708].
63
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