In his testimony, Langone expressed the following opinions (Engvall Brief, p. 101-102): (1)
that the hyperimmunization technique described in Example 1 for preparing the monoclonal antibodies
bound to the substrate was a procedure that optimized the production of antibodies having an affinity
of at least 10 liters/mole (Langone, ER 3503-11); (2) that the ELISA assay used to identify8
antibodies against AFP in example 1 removed low affinity antibodies resulting in antibodies having
affinity constants “greater than 10 liters/mole” (Langone, ER 3527-28, 4236-38; Exhibit 130, page8
137, ¶ 3); (3) the sensitivity of the assay and the fact that both antibodies had to have a similar affinity
indicates that the example 1 antibodies have and affinity of “at least 10 liters/mole” (Langone, ER8
3496-3502); and (4) that the relatively short time to complete the assay indicates affinities “greater
than 10 liters/mole” (Langone, ER 3502-03, 3815-16; Exhibit E129, page 11, lines 26-29). We do8
not credit Langone’s testimony since no objective evidence has been identified which indicates why
8 6
the value for the affinity constant would be viewed as greater than 10 rather than greater than 10 ,
7 9 10
10 , 10 or 10 liters/mole. For example, Engvall has not pointed to any evidence that relates the
time to complete the assay (Langone opinion (4)) to any quantitative value for the affinity constant.
In other words, the evidence does not show that the person having ordinary skill in the art would not
7 9.
reach a conclusion that the affinity constant was “greater than 10 ,” “greater than 10 ” or “greater
than 10 .”10
In any event, evidence of record contradicts most of Langone’s opinions. With respect to
hyperimmunization, Langone also testified that the hyperimmunization process does not always and
necessarily make high affinity antibodies. Langone, ER 3873, line 6 - ER 3874, line 18. Thus, the
record does not establish that a person having ordinary skill in the art repeating Engvall’s example
1 would necessarily obtain high affinity antibodies for AFP using the hyperimmunization technique.
As to the ELISA assay removing low affinity antibodies, Engvall and her coinventors
published an article (E67) discussing radioimmunoassay using monoclonal antibodies to AFP. The
article was published in 1982, after Engvall’s U.S. parent application filing date. Like Engvall’s
example 1, an ELISA assay was used to screen for anti-AFP activity. E67, p.11. Positive cultures
identified by the ELISA assay were cloned and used for radioimmunoassay. E69, p.11. The authors
report that this procedure did not always provide high affinity monoclonal antibodies. The article
states:
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