Apparently recognizing that the affinity of the carrier-bound antibody could not be calculated
from the data in Engvall’s example 1, Bergland and Langone expressed their opinions that the affinity
of the constant for the carrier-bound antibody would be about the same as the enzyme labeled (liquid-
phase) antibody. ER 1959; ER 3496. As we indicated above, the asserted value for the enzyme-
labeled antibody was too speculative to provide reasonable direction to the person of ordinary skill
in the art to constitute a written description of the lower limit of 10 liters per mole. Thus, their8
testimony that the affinity constant for the antibody bound to a solid carrier is about the same as the
affinity constant for the liquid-phase antibody is equally speculative.
In any event, Bergland’s and Langone’s opinions as to the magnitude of the affinity constant
of the carrier bound antibody are questionable. The Rodbard publication, in noting the complexity
of the reaction system involved in with immunometric assays, cautions that “numerical evaluation of
the curves is essential, and intuitive predictions are likely to be misleading.” GCX141, p. 81, col. 1.
In addition, the “affinity” of the antibody bound to a carrier may be artificially increased. Thus, David
testified that in an ELISA type of assay
antigen is applied, for example, to the bottom of a microtiter plate to
create a solid-phase reagent which reacts with the monoclonal
antibody. The microenvironmental concentration of antigen on the
solid phase is artificially increased, causing the antigen to react with
antibodies of lower affinity.
DR116 . David’s testimony is consistent with other objective evidence. A publication titled58
“Antibodies A Laboratory Manual” (DCX83 ) states the following:59
Antigens immobilized on solid supports at high concentrations
promote high avidity, bivalent bonding.
When an antibody binds to an antigen on a solid phase, the
interaction is biphasic, and two factors, in addition to the intrinsic
58
Engvall has moved for suppression of Dr. Gary David’s declaration on the basis that is argumentative
and misleading. Engvall et al. Motion under 37 C.F.R. § 1.656(h) to Suppress Certain Evidence Offered by David et al.
(Paper 325), pp. 15-18 The motion is denied. The matters raised go to the weight of the evidence rather than its
admissibility.
59
Engvall has moved to suppress this document. Engvall et al. Motion under 37 C.F.R. § 1.656(h) to
Suppress Certain Evidence Offered by David et al. (Paper 325), p. 12. The motion is denied. Engvall asserts that as a
laboratory manual published in 1988 it is irrelevant and hearsay. We consider the document relevant to the opinions
expressed by Langone and Bergland with respect to the affinity constant of the bound antibody. In addition, had we been
asked we might have taken official notice of the scientific facts presented therein. FRE 201.
36
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