In her brief, Engvall summarizes the evidence of conception as follows (Engvall Brief, pp. 20-
21):
• Dr. Ruoslahti’s 1978 Grant Applications described his plans
to obtain high affinity antibodies to AFP, to have Uotila make
monoclonal antibodies and test them, and to use monoclonal
antibodies in diagnostic applications, including assaying for AFP.
• In the Fall of 1978, Dr. Engvall was throughly familiar with
the use of polyclonal antibodies in the sandwich assay, having taught
it to undergraduate students, having published descriptions and
illustrations of it, having carried out sandwich assays, having carried
out sandwich assays herself, and having taught and supervised Susan
Holbeck in carrying out sandwich assays.
• Susan Holbeck, Esther Oh, and Dr. Edward Hayman each
confirmed that in the Fall of 1978 Dr. Engvall came up with the idea
of using such high affinity monoclonal antibodies in a sandwich assay.
[Emphasis added, references to Engvall’s brief deleted.]
Engvall’s evidence is, in our view, insufficient to show that the inventors had an appreciation
of the use of monoclonal antibodies having an affinity constant of at least about 10 liters/mole.8
Engvall argues at pages 14 to 19 of her reply brief that
Engvall appreciated the need for “high affinity” monoclonal
antibodies, that is, antibodies having an affinity constant of at least
about 10 liters per mole.8
In making this argument, Engvall notes that one of the inventors, Dr. Ruoslahti had been working
with AFP for many years. Engvall also notes that concentration of 20 nanograms or more of AFP
per milliliter was significant and any assay to be clinically useful would have to be sensitive enough
to detect AFP in a concentration of 20 nanograms per liter. Counsel calculates this to be 3x10-10
moles per liter and using the rule of thumb from the Parker text, arrives at a minimum acceptable
affinity constant of 3.3x10 liters per mole for AFP. And since the determination of the affinity9
constant is allegedly only accurate to an order of magnitude, this translates to a constant of 3.3x108
liters per mole. This value is within the scope of the count. Engvall also points to Dr. Uotila’s
testimony that she was looking for antibodies with a “high affinity” for AFP and that by “high affinity”
she meant affinity which was comparable to the affinity of the best available conventional antiserum.
Engvall reply brief, p 17. Engvall then states:
42
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