from the United States District Court for the District of
Delaware in No. 1:17-cv-00546-LPS, Chief Judge Leonard P.
Nicholas P. Groombridge, Paul, Weiss, Rifkind, Wharton &
Garrison LLP, New York, NY, argued for plaintiffs-appellants.
Also represented by Jennifer Gordon, Golda Lai, Peter Sandel,
Jacob Whitt, Jennifer H. Wu; Lois M. Kwasigroch, Kimberlin L.
Morley, Wendy A. Whiteford, Amgen Inc., Thousand Oaks, CA.
G. Unikowsky, Jenner & Block LLP, Washington, DC, argued
for defendant-appellee. Also represented by Bradford Peter
Lyerla, Aaron A. Barlow, Louis Fogel, Susan O'Brien,
Reyna, Hughes, and Stoll, Circuit Judges.
Inc. and Amgen Manufacturing Ltd. (collectively,
"Amgen") sued Coherus BioSciences Inc. for patent
infringement in the District of Delaware. The district court
dismissed Amgen's complaint for failure to state a claim,
and Amgen appeals. Because prosecution history estoppel bars
Amgen from succeeding on its infringement claim under the
doctrine of equivalents, we affirm the order of the district
therapeutic proteins are a class of biologic medicines that
are manufactured inside living cells. Before a protein can be
therapeutically useful, it must first be purified from
contaminants. Amgen's U.S Patent No. 8, 273, 707 claims
methods of purifying proteins using hydrophobic interaction
chromatography ("HIC"). A HIC column contains a
solid, hydrophobic matrix and "is used to separate
proteins on the basis of hydrophobic interactions between the
hydrophobic moieties of the protein and insoluble,
immobilized hydrophobic groups on the matrix." '707
patent col. 1 ll. 36-39. In a HIC purification, a buffered
salt solution containing the desired protein and associated
impurities is first poured onto a HIC column. Id. at
col. 1 ll. 40-41. This is known as the "loading"
step. The salt in the buffer exposes the hydrophobic regions
of the protein and causes them to adsorb (i.e.,
attach) onto the hydrophobic groups on the column matrix.
See id. at col. 1 ll. 41-44. The impurities are then
washed out of the column with a buffered salt solution while
the desired protein remains attached to the matrix. See
id. at col. 4 ll. 27-29. Finally, molecules of the
desired protein are detached (or "eluted") by
pouring a buffer solution with a lower salt concentration
through the column. See id. at col. 1 ll. 44-49.
"Usually, a decreasing salt gradient is used to elute
proteins from a column. As the ionic strength decreases, the
exposure of the hydrophilic regions of the protein increases
and proteins elute from the column in order of increasing
hydrophobicity." Id. at col. 1 ll. 45-49.
the loading step, only a finite amount of protein can bind to
the matrix. If too much protein is loaded on the column,
"'breakthrough' or loss of protein to the
solution phase before elution" will occur. Id.
at col. 3 ll. 40-41. The '707 patent claims a process
that reduces breakthrough, or in other words, increases the
"dynamic capacity" of a HIC column. Dynamic
capacity refers to "the maximum amount of protein in
solution which can be loaded onto a column without
significant breakthrough or leakage of the protein into the
solution phase of a column before elution." Id.
at col. 3 l. 65-col. 4 l. 3.
art methods of increasing a HIC column's dynamic capacity
included using a higher salt concentration in the buffer
solution. See id. at col. 3 ll. 37-38. This resulted
in other problems, however, as "high salt can be
detrimental to protein stability. High salt increases the
viscosity of a solution, results in increased formation of
aggregates, results in protein loss due to dilution and
filtration of the protein after elution from the column, and
can lead to reduced purity." Id. at col. 3 ll.
41-45. Instead of increasing the concentration of a single
salt, the '707 invention:
provides combinations of salts useful for increasing the
dynamic capacity of an HIC column compared with the dynamic
capacity of the column using separate salts alone. These
combinations of salts allow for a decreased concentration of
at least one of the salts to achieve a greater dynamic
capacity, without compromising the quality of the protein
Id. at col. 2 ll. 9-15. All of the '707 claims
require a salt combination chosen from one of three pairs:
citrate and sulfate, citrate and acetate, or sulfate and
acetate. Representative claim 1 recites:
1. A process for purifying a protein on a hydrophobic
interaction chromatography column such that the dynamic
capacity of the column is ...