United States District Court, D. Delaware
OPINION & ORDER
Honorable Timothy B. Dyk United States Circuit Judge.
4, 2017, Baxalta Inc. and Baxalta GmbH (together,
"Baxalta") brought suit against Genentech, Inc. and
Chugai Pharmaceutical Co., Ltd., alleging infringement of
U.S. Patent No. 7, 033, 590 ("the '590 patent")
by the manufacture, use, sale, offer to sell, and importation
of an antibody used to treat hemophilia A and known as
emicizumab or ACE910, marketed under the brand name Hemlibra.
On December 14, 2017, Baxalta moved for a preliminary
injunction barring further sales or offers to sell Hemlibra
in the United States, with exceptions for certain patients.
In addition to two rounds of briefing, the Court held an
evidentiary hearing on Baxalta's motion on June 13 and
14, 2018, and heard oral argument on July 2, 2018. Baxalta
having failed to meet its burden for showing the propriety of
preliminary injunctive relief, the motion for a preliminary
injunction is DENIED. This opinion constitutes the
Court's findings of fact and conclusions of law pursuant
to Federal Rule of Civil Procedure 52(a).
filed its complaint on May 4, 2017, alleging infringement of
the '590 patent. Compl. ¶¶ 37-51, ECF No. 1.
Genentech answered on June 30, denying Baxalta's
allegations and counterclaiming for declaratory judgment of
noninfringement and invalidity. Answer & Countercl.
¶¶ 37-51, 120-49, ECF No. 9. With the Court's
leave, Baxalta has since amended its complaint to add
allegations of willfulness. 1st Am. Compl. ¶¶
37-44, 60-65, ECF No. 239.
December 14, 2017, Baxalta moved for a preliminary injunction
against Genentech (but not Chugai). Mot. Prelim. Inj. 2, ECF No.
41; Prop. Prelim. Inj. Order 1, ECF No. 42-1. Although
Baxalta initially asserted seven claims of the '590
patent, Bax. Mem., at v, ECF No. 42, it later filed notice
that it would assert only claim 1 for purposes of this
motion, Notice 1, ECF No. 106.
4, 2018, this action was reassigned to the undersigned,
sitting by designation. Genentech thereafter filed its
opposition to Baxalta's motion, Gen. Mem., ECF No. 154,
and Baxalta filed its reply, Bax. Reply, ECF No. 180. A group
of potentially affected hemophilia patients, Patients for
Access to Advanced Hemophilia Therapy (PAAHT), filed a brief
as amicus curiae in opposition to Baxalta's motion.
Amicus Br., ECF No. 190. Finally, the parties filed
supplemental letters concerning the claim-construction issues
bearing on Baxalta's motion. Gen. Ltr., ECF No. 201; Bax.
Ltr., ECF No. 202.
Court held a two-day evidentiary hearing on Baxalta's
motion on June 13 and 14, 2018. See Tr., ECF Nos.
214-15. The Court heard oral argument on the motion on July
2, 2018. See Oral Arg. Tr., ECF No. 229. The parties
then submitted proposed findings of fact and conclusions of
law, as well as replies thereto. See Bax. Prop. F.
& C, ECF No. 230; Gen. Prop. F. & C, ECF No. 232;
Bax. Reply F. & C, ECF No. 242; Gen. Reply F. & C,
ECF No. 244. The parties submitted a list of exhibits to be
included in the preliminary-inunction record and their
objections thereto. See Joint Ltr., ECF No. 245.
Treating Hemophilia A
body stops bleeding by relying on blood coagulation, also
known as clotting, which is accomplished through a cascade of
reactions between proteins, including those proteins known as
clotting factors. See Aledort Decl. ¶¶
13-14, ECF No. 46; Sheehan Decl. ¶ 35, ECF No. 111.
Several of these factors are identified by Roman numerals,
e.g., Factor I or Factor IX, and when activated are
identified with an appended a, e.g., Factor IXa.
Aledort Decl. ¶ 13. The relevant steps in this clotting
cascade here involve the coming together of Factor Villa and
Factor IXa. See Id. These two activated factors form
a complex, which in turn activates Factor X. See
id.; Sheehan Decl. ¶ 36. Several steps later, the
cascade yields a protein known as fibrin, and a blood clot is
formed. See Aledort Decl. ¶ 13; Sheehan Decl.
A is a genetic disorder in which Factor VIII is reduced,
defective, or absent. See Aledort Decl. ¶ 14;
Sheehan Decl. ¶ 42. This amounts to a roadblock in the
clotting cascade, and hemophilia A patients therefore suffer
from a reduced ability to form quick and effective blood
clots. Aledort Decl. ¶ 14; Sheehan Decl. ¶ 42.
Hemophilia A can be classified as mild, moderate, or severe
based on the level of Factor VIII activity. See
Sheehan Decl. ¶ 43.
common treatment for hemophilia A patients is infusion with a
Factor VIII replacement, either natural or synthetic. Aledort
Decl. ¶ 14; Callaghan Decl. ¶ 15, ECF No. 109.
Factor VIII replacement therapy can be administered either as
an ongoing prophylactic therapy and/or on-demand to treat
bleeding episodes. See Tr. 205:24-206:13.
Baxalta's Factor VIII therapies include two products at
issue here: Advate and Adynovate. See Bakewell Decl.
¶ 33, ECF No. 43; Tr. 299:8-14.
up to 35% of patients with hemophilia A develop Factor VIII
inhibitors, antibodies produced by the immune system that
block the effect of the Factor VIII replacement. See
Tr. 163:21-22; Aledort Decl. ¶ 15; Young Decl. ¶
20, ECF No. 110. These are known as inhibitor patients.
See, e.g., Aledort Decl. ¶ 16. Prior to the
introduction of Hemlibra, there had been two approaches to
treatment of inhibitor patients. Somewhere between 40% and
70% of inhibitor patients (who cannot receive Factor VIII
therapy) are able to build up a tolerance for Factor VIII
therapy through routine injection of the factor in a therapy
known as immune tolerance induction (ITI). See
Aledort Decl. ¶ 16; Young Decl. ¶¶ 22-23. ITI
requires daily infusion of Factor VIII for months or even
years before it is clear whether it has been successful.
Callaghan Decl. ¶ 16; Young Decl. ¶ 22. If
inhibitor patients are unable to achieve such a tolerance,
they are unable to receive Factor VIII therapies.
See Callaghan Decl. ¶ 16; Young Decl. ¶
second method of treatment for inhibitor patients involves
bypassing agents (BPAs), which bypass the Factor VIII step in
the clotting cascade. Aledort Decl. ¶ 17; Young Decl.
¶ 24. This includes Baxalta's BPA product, Feiba.
See Bakewell Decl. ¶ 33; Young Decl. ¶ 24;
Tr. 299:8-14. Feiba is FDA-approved only for inhibitor
patients. See, e.g., Aledort Decl. Ex. J, at 1, ECF
No. 46-10. BPAs can be used in two ways, on-demand when a
bleeding episode occurs and/or on a regular schedule as
prophylaxis. Aledort Decl. ¶ 17; Young Decl. ¶ 25.
But BPAs, like Factor VIII replacement therapies, must be
infused, which may impose a substantial treatment burden on
patients and their families. In particular, the infusion can
take up to an hour as often as every other day in order to
achieve the desired prophylactic effect. See
Callaghan Decl. ¶¶ 20, 26; Young Decl. ¶ 29.
(Baxalta's expert, Dr. Aledort, testified that he did not
think infusion takes as long as described, but he was unable
to provide an alternative estimate. See Tr.
181:16-182:23.) Moreover, the infusion must be administered
directly into a vein or through a central venous-access
device, more commonly known as a port, and each of these
methods entails risk of infection or venous-access issues.
See, e.g., Callaghan Decl. ¶ 49; Young Decl.
¶¶ 19, 25.
the accused product, treats hemophilia A in yet another
manner. In general, antibodies are K-shaped, with two arms
connected by disulfide bonds. Strohl Decl. ¶ 22, ECF No.
112. Each arm of the Y shape contains two
polypeptides known as the heavy chain and the light chain.
See Id. Hemlibra is a bispecific antibody, meaning
that the heavy chains on its two arms are not identical.
See Krishnaswamy Decl. ¶¶ 55, 60, ECF No.
47; Strohl Decl. ¶¶ 38, 53. One of its arms binds
to Factor IX (or IXa) and the other binds to Factor X.
See Krishnaswamy Decl. ¶ 55, 60; Strohl Decl.
¶ 53. Hemlibra replaces Factor Villa in the clotting
cascade, activates Factor X, and allows the process to
continue to clot formation despite the deficiency in Factor
VIII caused by hemophilia A. See Krishnaswamy Decl.
¶ 61, Strohl Decl. ¶¶ 178-79. Unlike BPAs,
Hemlibra can be administered by a once-weekly subcutaneous
injection using a syringe rather than by infusion. Callaghan
Decl. ¶¶ 47-48; Young Decl. ¶¶ 50-53.
Food and Drug Administration (FDA) approved Hemlibra for
hemophilia A patients with inhibitors on November 16, 2017,
and Genentech launched the product in the United States for
that population later that month. Bakewell Decl. ¶ 40.
For the treatment of noninhibitor patients, the FDA has
granted Hemlibra Breakthrough-Therapy Designation and
Priority Review, Tr. 591:18-24, which generally indicates
that the FDA will undertake an expedited review on the basis
of promising clinical data and a treatment's expected
medical benefits, Tr. 589:2-15. Pursuant to this priority
review, Genentech expects approval of Hemlibra for
noninhibitor patients no later than early October 2018-and
possibly sooner. See Tr. 592:1-593:24. In the
meantime, some small number of patients falling within the
noninhibitor category are being prescribed Hemlibra by their
doctors off-label, i.e., notwithstanding the lack of FDA
approval for that patient population. See, e.g., Tr.
summarize: there are four products at the heart of this
litigation. Baxalta offers two primary Factor VIII
replacement therapies for noninhibitor patients: Advate and
Adynovate. It also offers a BPA product for inhibitor
patients: Feiba. All three Baxalta products can be
administered prophylactically and/or on-demand to treat
particular bleeding episodes. See, e.g., Tr.
552:15-554:5. None of Baxalta's products practices the
'590 patent. Bakewell Decl. ¶ 55. Genentech's
product, emicizumab, is marketed as Hemlibra. It is
administered only as prophylaxis. See, e.g., Tr.
206:14-23. Hemlibra competes with Feiba in the inhibitor
market, and Hemlibra will compete with Advate and Adynovate
in the noninhibitor market once FDA approval is forthcoming.
The Proposed Injunction
with its motion for a preliminary injunction, Baxalta filed a
proposed order that would bar Genentech from selling or
offering to sell Hemlibra to any noninhibitor patients and
would allow sales to inhibitor patients only if they (1) had
already been receiving Hemlibra or (2) met a set of criteria
generally indicating some heightened need for Hemlibra
treatment. See Prop. Prelim. Inj. Order ¶¶
2, 4, 6. Those criteria included a documented annual bleed
rate over a certain threshold; a documented, spontaneous
life- or limb-threatening bleeding episode; and documented
venous-access issues. Id. ¶ 4(b)-(c). The
proposed order did not appear to carve out noninhibitor
patients who have already been receiving Hemlibra as part of
the clinical trials. See Id. ¶ 6; Tr. 199:1-11.
the hearing on its motion, Baxalta agreed to broaden the
scope of this carveout from its proposed injunction. Tr.
309:23-310:8. In particular, Baxalta agreed "to amend
its proposed carveout to extend to all inhibitor patients for
FDA-approved use at this time, assuming appropriate steps
were taken to ensure that off-label sales did not
occur." Tr. 310:4-8. Following the hearing, Baxalta
submitted an amended proposed injunction order that would bar
Genentech from selling or offering to sell Hemlibra except
(a) "patients with inhibitors";
(b) "patients in connection with clinical trials";
(c) "patients without inhibitors who had received
HEMLIBRA (whether in connection with clinical studies
pursuant to 35 USC § 271(e)(1) or commercially) prior to
entry of [the preliminary injunction]"; and
(d) "patients without inhibitors whose doctor has
certified that the patient has a medically diagnosed
condition that makes intravenous administration of Factor
VIII replacement therapy impracticable."
Am. Prop. Prelim. Inj. Order ¶ 4, ECF No. 218. The
proposed order would further require Genentech to institute
some mechanism for doctors prescribing Hemlibra to certify
that their patient falls within one of these categories.
Id. ¶ 5(b). It would also require Genentech to
"make reasonable efforts to confirm" the accuracy
of those certifications. Id. ¶
plaintiff seeking a preliminary injunction must establish 
that he is likely to success on the merits,  that he is
likely to suffer irreparable harm in the absence of
preliminary relief,  that the balance of equities tips in
his favor, and  that an injunction is in the public
interest." Winter v. Nat. Res. Def. Council,
Inc., 555 U.S. 7, 20 (2008); accord Benisek v.
Lamone, 138 S.Ct. 1942, 1943-44 (2018) (per curiam);
Osorio-Martinez v. Att'y Gen. U.S., 893 F.3d
153, 178 (3d Cir. 2018); Metalcraft of Mayville, Inc. v.
Toro Co., 848 F.3d 1358, 1363-64 (Fed. Cir. 2017).
recently, the Supreme Court has reiterated that "[a]s a
matter of equitable discretion, a preliminary injunction does
not follow as a matter of course from a plaintiffs showing of
a likelihood of success on the merits," rather, the
other factors must also be considered and could also support
the denial of a preliminary injunction. Benisek, 138
S.Ct. at 1943-44. In Benisek, the Supreme Court
affirmed the denial of a preliminary injunction even assuming
a likelihood of success on the merits, because "the
balance of equities [including a lack of diligence] and the
public interest tilted against" granting an injunction.
the parties have taken starkly different positions on the
merits, i.e., the invalidity and infringement of the '590
patent. Both issues present difficult questions best resolved
based on a fuller record. But, as in Benisek, even
assuming Baxalta has some likelihood of success on the
merits, its failure to establish two other ...