ELI LILLY AND COMPANY v. HOSPIRA, INC.

Filing 89

ENTRY ON CROSS MOTIONS FOR SUMMARY JUDGMENT - Eli Lilly and Company ("Lilly") initiated this Hatch-Waxman litigation against Defendant Hospira, Inc. ("Hospira") for infringement of Lilly's U.S. Patent 7,772,209 ("the & #039;209 Patent"). On April 6, 2018, Hospira filed a Motion for Summary Judgment of Non- Infringement on its New Drug Application ("NDA") No. 208746, on the bases that there is no plausible theory pled under which Hospira would infri nge the patent in suit and the doctrine of equivalents does not expand the scope of Lilly's patent to include Hospira's product. (Filing No. 73 .) On April 27, 2018, Lilly filed a Cross-Motion for Summary Judgment of Infringement. (Fili ng No. 78 .) Hospira's Motion for Summary Judgment of Non-Infringement (Filing No. 73) is DENIED and Lilly's Cross-Motion for Summary Judgment of Infringement pursuant to literal infringement and doctrine of equivalents (Filing No. 78) is GRANTED. (See Entry.)Signed by Judge Tanya Walton Pratt on 6/15/2018. (NAD)

UNITED STATES DISTRICT COURT
SOUTHERN DISTRICT OF INDIANA
INDIANAPOLIS DIVISION
ELI LILLY AND COMPANY,

)
)
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) Case No. 1:16-cv-03460-TWP-MPB
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)

Plaintiff,
v.
HOSPIRA, INC.,
Defendant.

ENTRY ON CROSS MOTIONS FOR SUMMARY JUDGMENT
Before the Court are the parties’ cross-motions for summary judgment. Eli Lilly and
Company (“Lilly”) initiated this Hatch-Waxman litigation against Defendant Hospira, Inc.
(“Hospira”) for infringement of Lilly’s U.S. Patent 7,772,209 (“the ’209 Patent”). On April 6,
2018, Hospira filed a Motion for Summary Judgment of Non-Infringement on its New Drug
Application (“NDA”) No. 208746, on the bases that there is no plausible theory pled under which
Hospira would infringe the patent in suit and the doctrine of equivalents does not expand the scope
of Lilly’s patent to include Hospira’s product. (Filing No. 73.) On April 27, 2018, Lilly filed a
Cross-Motion for Summary Judgment of Infringement. (Filing No. 78.) For the reasons stated
below, the Court grants Lilly’s Cross-Motion for Summary Judgment, and denies Hospira’s
Motion for Summary Judgment.
I.

BACKGROUND

The ‘209 Patent describes a method of administering the chemotherapy drug, pemetrexed
disodium, with a pretreatment regimen of vitamin B12 and folic acid (the “pretreatment regimen”),
which is marketed by Lilly under the trade name ALIMTA®. The ‘209 Patent has been the subject
of previous trials before this Court. See Eli Lilly and Co. v. Teva Parenteral Medicines, Inc., 126

F. Supp.3d 1037, 1038 (S.D. Ind. 2015). 1 Two of those cases specifically concerned generic drug
manufacturers that sought to market a generic version of ALIMTA® including labeling that
induced physicians to direct patients to take folic acid and vitamin B12 in accordance with the
pretreatment claims in the ‘209 Patent. Specifically, in the Teva case, the pretreatment regimen
and whether the steps of the claimed method could be attributed to a single actor was at issue. Id.
On February 1 and 2, 2018, this Court held a bench trial in Eli Lilly & Co. v. Dr. Reddy’s
Laboratories, Ltd., No. 1:16-cv-308-TWP-MPB (the “Dr. Reddy’s Case”) involving primarily the
same alleged infringing drug product at issue in this action: pemetrexed ditromethamine. 2
During prosecution of its patent application for ALIMTA®, the U.S. Patent and Trademark
Office originally rejected claim 2 of the ‘209 Patent as being anticipated by a prior art article,
Arsenyan et.al. (“Arsenyan”). Arsenyan concerned the administration of the compound
methotrexate. 3 (Filing No. 76-3 at 105.) To avoid rejection of its patent in view of Arsenyan,
Lilly narrowed the scope of its claims from a broad category of antifolates to specifically
pemetrexed disodium. (Filing No. 76-3 at 123.)
Similar to the issue in Dr. Reddy’s Case, Hospira has also developed and designed a
competing pemetrexed drug product, which uses a salt base, tromethamine, rather than the sodium
base contained in Lilly’s product. 4 Hospira seeks to market its product in the form of a new product
that uses pemetrexed ditromethamine, unlike the generic drugs in previous trials before the Court.

1

The ‘209 Patent is also the subject of other pending infringement suits pending before this Court.
Because Hospira has conceded that many of the case-dispositive questions were all resolved against its interest in
the Court’s summary judgment ruling in the Dr. Reddy’s Case, the Court relies heavily on the analysis contained
therein in resolving the present cross-summary judgment motion in this case. (See Filing No. 79-3.)
2

3

Both methotrexate and pemetrexed fall within the broader antifolate group, but they target different enzymes. (See
Filing No. 79 at 24.)

4

Although Hospira’s drug label is slightly different, Hospira’s drug product is identical to that in the Dr. Reddy’s
Case. (Filing No. 74-1 at 15.)

2

In large part, the issues in the present case and the Dr. Reddy’s Case are the same. However, unlike
Dr. Reddy’s label, Hospira’s label instructs that it can be reconstituted in saline solution (like
ALIMTA®) in addition to 5% dextrose solution (like Dr. Reddy’s product). (Filing No. 49-29;
Filing No. 74-1 at 15-16.)
A point of contention between the parties is whether pemetrexed ditromethamine was
excluded (thus, designated public use) from the claims during patent prosecution by Lilly’s
specification and narrowing amendment from the term “antifolates” to “pemetrexed disodium”.
The liquid solution of both chemical compounds results in pemetrexed treatment, but the powdered
solid form of the two products differ as a result of the different salt compounds used. The patient
receives the liquid solution intravenously. Both products are sold in solid form. (Filing No. 74-1
at 17; Filing No. 79 at 14.) Claim 12 of the ‘209 Patent, a dispositive issue (agreed by the parties)
regarding whether or not Hospira’s product infringes was construed in the Dr. Reddy’s Case by
this Court. (Filing No. 79-3 at 6.) Claim 12 reads as follows:
12. An improved method for administering pemetrexed disodium to a patient in
need of chemotherapeutic treatment, wherein the improvement comprises:
a) administration of between about 350 µg and about 1000 µg of folic acid
prior to the first administration of pemetrexed disodium;
b) administration of about 500 µg to about 1500 µg of vitamin B12, prior to the
first administration of pemetrexed disodium; and
c) administration of pemetrexed disodium.
(Filing No. 1-1 at 9). The Court construed administration of pemetrexed disodium to refer to a
liquid administration of pemetrexed disodium. (No. 1:16-308-TWP-MPB, ECF 199 at 9.) In the
claim construction, the Court did not address the science of what happens when pemetrexed
disodium is dissolved in aqueous solution in construing claim 12. Id. at 8-9. Nevertheless, Hospira
and Lilly agree that based on the Court’s construction in the Dr. Reddy’s Case, that claim 12 would
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necessarily encompass any solution containing pemetrexed and sodium ions because it is
undisputed that when pemetrexed disodium is dissolved in solution, pemetrexed disodium would
not exist as an ionically bonded compound. (Filing No. 79 at 9; Filing No. 79-3 at 8). Rather the
liquid solution contains pemetrexed and disodium (or tromethamine) ions disassociated from one
another. 5 Id. Thus, the solution that is administered to the patient would not contain pemetrexed
disodium as an ionically bonded salt, and instead would contain disassociated pemetrexed and
sodium ions in solution. The Court directs the parties to the Dr. Reddy’s Case for the analysis of
the claim construction ruling, which binds the identical claim at issue in this case.
II.

LEGAL STANDARD

The purpose of summary judgment is to “pierce the pleadings and to assess the proof in
order to see whether there is a genuine need for trial.” Matsushita Electric Industrial Co. v. Zenith
Radio Corp., 475 U.S. 574, 587 (1986). Federal Rule of Civil Procedure 56 provides that summary
judgment is appropriate if “the pleadings, depositions, answers to interrogatories, and admissions
on file, together with the affidavits, if any, show that there is no genuine issue as to any material
fact and that the moving party is entitled to a judgment as a matter of law.” Hemsworth v.
Quotesmith.Com, Inc., 476 F.3d 487, 489-90 (7th Cir. 2007). In ruling on a motion for summary
judgment, the court reviews “the record in the light most favorable to the nonmoving party and
draw[s] all reasonable inferences in that party’s favor.” Zerante v. DeLuca, 555 F.3d 582, 584
(7th Cir. 2009) (citation omitted). However, “[a] party who bears the burden of proof on a
particular issue may not rest on its pleadings, but must affirmatively demonstrate, by specific
factual allegations, that there is a genuine issue of material fact that requires trial.” Hemsworth,
476 F.3d at 490 (citation omitted). “In much the same way that a court is not required to scour the

5

Hospira does not agree with this Court’s claim construction ruling, however it concedes that under this construction
its product would infringe. (Filing No. 79-3 at 7-8.)

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record in search of evidence to defeat a motion for summary judgment, nor is it permitted to
conduct a paper trial on the merits of a claim.” Ritchie v. Glidden Co., 242 F.3d 713, 723 (7th Cir.
2001) (citation and internal quotations omitted). Finally, “neither the mere existence of some
alleged factual dispute between the parties nor the existence of some metaphysical doubt as to the
material facts is sufficient to defeat a motion for summary judgment.” Chiaramonte v. Fashion
Bed Grp., Inc., 129 F.3d 391, 395 (7th Cir. 1997) (citations and internal quotations omitted). This
notion applies equally where, as here, opposing parties each move for summary judgment in their
favor pursuant to Rule 56. I.A.E., Inc. v. Shaver, 74 F.3d 768, 774 (7th Cir. 1996).
III. DISCUSSION
Lilly argues that Hospira’s product infringes under two theories: literal infringement and
the doctrine of equivalents. (Filing No. 79 at 18, 23.) Hospira raises three non-infringement
defenses to Lilly’s infringement theories. (Filing No. 74-1 at 5.) The Court will address each
argument in turn.
A.

Literal Infringement
“Literal infringement requires a patentee to prove by a preponderance of the evidence that

every limitation of the asserted claim is literally met by the allegedly infringing device.” Biovail
Corp. Intern. v. Andrx Pharmaceuticals, Inc., 239 F. 3d 1297, 1302 (Fed. Cir. 2001). Lilly
contends that Hospira’s product will literally infringe when it is reconstituted in saline according
to Hospira’s proposed labeling instructions. (Filing No. 79 at 18.) It is undisputed as manufactured
pemetrexed ditromethamine is a separate, distinct compound from the claimed pemetrexed
disodium. (Filing No. 74-1 at 24; Filing No. 79 at 18.) Thus, in solid form Hospira’s product does
not contain pemetrexed disodium. Hospira’s product may be reconstituted and diluted pursuant to

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either saline preparation or dextrose preparation. (Filing No. 74-1 at 24.) Lilly contends that the
saline preparation will literally infringe the ‘209 Patent.
Lilly has presented unrebutted expert testimony as to the chemical makeup of Hospira’s
product reconstituted in saline solution that would be administered to a patient. (Filing No. 78-1;
Filing No. 78-2.) Additionally, Hospira concedes that under the Court’s claim construction in the
Dr. Reddy’s Case, that its product, in accordance with its proposed labeling, literally infringes the
‘209 Patent. (Filing No. 79-3 at 12.) Saline solution contains sodium chloride, which also
dissociates (at the molecular level) completely into sodium and chloride ions when dissolved in
the solution. (Filing no. 79-2 at 12-13.) Because it is undisputed that, in liquid administration,
pemetrexed is the active moiety that exerts chemotherapeutic effect to the patient, in that the
pemetrexed dissociates from the ionic salt bond it was attached to, it makes no difference whether
the ionic bond started as pemetrexed disodium or pemetrexed ditromethamine. (Filing No. 79-2
at 13.) With regards to the saline dilution and reconstitution, the resulting solutions in both
instances would contain dissociated pemetrexed ions and sodium ions—that is pemetrexed
disodium. Id. at 15. It is of no moment if the solution also contains tromethamine ions (as in
Hospira’s product), so long as the solution contains pemetrexed and a corresponding number of
sodium ions (two per pemetrexed ion). Id. Accordingly, administering Hospira’s NDA products
reconstituted and diluted in saline literally infringe the ‘209 Patent. Thus, Lilly’s Cross-Motion
for Summary Judgment of literal infringement is granted.
B.

Doctrine of Equivalents
“The doctrine of equivalents extends the right to exclude beyond the literal scope of the

claims.” Johnson & Johnston Associates, Inc. v. R.E. Service Co., Inc., 285 F.3d 1046, 1053 (Fed.
Cir. 2002). “The doctrine of equivalents allows the patentee to claim those insubstantial alterations

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that were not captured in drafting the original patent claim but which could be created through
trivial changes.” Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 733 (2002).
The doctrine of equivalents is restricted by the “all limitations” rule and the prosecution history
estoppel rule by limiting the range of equivalents when claims have been narrowed. See Pozen
Inc. v. Par Pharmaceutical, Inc., 696 F.3d 1151, 1167. Hospira argues that Lilly’s doctrine of
equivalents infringement claim is foreclosed by prosecution history estoppel and the disclosure
dedication rule. The Court will address each of these threshold arguments in turn.
1.

Prosecution History Estoppel

Hospira presents defenses similar to those of Dr. Reddy’s in the Dr. Reddy’s Case. It is
undisputed that Lilly narrowed its broader antifolates claim to pemetrexed disodium during
prosecution to avoid Arsenyan prior art. It is also undisputed that Hospira’s product would fall
within the scope of the original antifolates claim. Under Festo, Lilly’s narrowing amendment
triggers a presumption of surrender that Lilly must rebut to sustain its doctrine of equivalents claim.
Festo, 535 U.S. at 725. Festo held three exceptions to defeat prosecution history estoppel:
The equivalent may have been unforeseeable at the time of the application; the
rationale underlying the amendment may bear no more than a tangential relation to
the equivalent in question; or there may be some other reason suggesting that the
patentee could not reasonably be expected to have described the insubstantial
substitute in question. In those cases the patentee can overcome the presumption
that prosecution history estoppel bars finding an equivalence.
Id. at 740-41. In contrast to Dr. Reddy’s argument on prosecution history estoppel, Hospira agrees
that there are three independent ways to overcome the presumption that prosecution history
estoppel bars Lilly’s doctrine of equivalents claim. (Filing No. 74-1 at 28.) Nevertheless, Hospira
argues that Lilly cannot meet any of the three possible grounds for rebuttal to apply. Id. at 31. In
the Dr. Reddy’s Case, the Court found that the tangential exception applied, and the Court will
focus on that exception in the case at bar.
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Hospira contends that Lilly’s amendment, made during prosecution of the ‘209 Patent,
related directly to the alleged equivalent pemetrexed ditromethamine, rather than a tangential
relationship because Lilly emphasized repeatedly that its invention concerned pemetrexed
disodium. Id. at 33. Lilly responds that the rationale for amending the ‘209 Patent claims from
“antifolate” to “pemetrexed disodium” bore no more than a tangential relation to the particular salt
form of pemetrexed (disodium as claimed versus ditromethamine used by equivalent). (Filing No.
79 at 23.) Moreover, Lilly explains that a person of skill in the art (“POSA”) would understand
that the rationale for the amendment was to distinguish pemetrexed from other active antifolates
such as methotrexate as it is undisputed that Arsenyan nor the prosecution history discuss different
salt forms of pemetrexed. Id. at 24.
On this issue, in the Dr. Reddy’s Case, the Court relied on Regents of University of Cal. v.
Dakocytomation Cal. Inc., where the federal circuit held that a patentee’s narrowing amendment
that centered on a method of blocking to avoid prior art that did not involve blocking was tangential
to the particular nucleic acid used to accomplish the blocking. 517 F. 3d 1364, 1378 (Fed. Cir.
2008). The patent at issue in that case claimed “blocking nucleic acid” which was construed by
the district court to involve human DNA, whereas the accused product used synthetic (not human)
nucleic acids referred to as peptide nucleic acids. Id. The use of synthetic nucleic acids to
accomplish the blocking method fell within the original broader claims, but was subsequently
removed by the amendment.

In reversing the district court’s summary judgment of non-

infringement, the federal circuit held “[t]he prosecution history therefore reveals that in narrowing
the claim to overcome the prior art rejections, the focus of the patentees’ arguments centered on
the method of blocking—not on the particular type of nucleic acid that could be used for blocking.”
Id. Thus, the federal circuit found the narrowing amendment was tangential.

8

Lilly also cites another line of cases that demonstrate that “the tangentiality exception has
routinely been applied in cases where the issued claims have been narrowed in a manner that
excludes the accused equivalent.” (Filing No. 79 at 26.) See Insituform Technologies, Inc., v. CAT
Contracting, Inc., 385 F.3d 1360 (Fed. Cir. 2004); Pfizer Inc., v. Teva Pharmaceuticals U.S.A.,
Inc., 882 F. Supp. 2d 643 (D. Del. 2012).

Lilly’s amendment focused on distinguishing

pemetrexed (the active antifolate) as opposed to methotrexate (a different antifolate) in that the
‘209 patent was drafted to protect a method of reducing toxicity associated with the administration
of pemetrexed disodium. (Filing No. 79 at 28-29). A POSA would regard the salt form of the
antifolate (pemetrexed) as peripheral to the amendment. Id. at 29. Because the tangentiality
exception applies, an independent and dispositive basis under Festo, Lilly is not estopped from
pursuing infringement under the doctrine of equivalents. The Court need not discuss Hospira’s
remaining arguments regarding the other two Festo exceptions (the foreseeability of tromethamine
or that Lilly could have drafted the ‘209 Patent to claim pemetrexed ditromethamine).
2.

Disclosure Dedication Doctrine

Similar to the Dr. Reddy’s Case, Hospira also argues a second threshold issue in that Lilly
is barred from pursuing infringement under the doctrine of equivalents because of the disclosurededication rule. However, Hospira has invoked the doctrine on a different aspect of the ‘209
Patent’s specification than the one relied on by Dr. Reddy’s. Specifically, Hospira contends that
the “‘209 patent specification unambiguously discloses the administration of any ‘antifolate’” 6 and
further, that Lilly’s claim to pemetrexed disodium dedicated to the public use of any antifolate
other than pemetrexed disodium, including pemetrexed ditromethamine. (Filing No. 74-1 at 36.)
Lilly responds that pemetrexed ditromethamine was never disclosed in the specification of the

6

Hospira agrees that there are no fact issues to resolve regarding its disclosure-dedication doctrine argument, and that
the issue must be resolved on summary judgment. (Filing No. 79-3 at 11-12.)

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‘209 Patent, as an alternative or otherwise, and that Lilly prosecuted claims that encompassed
pemetrexed ditromethamine. (Filing No. 79 at 31.)
“[W]hen a patent drafter discloses but declines to claim subject matter … this action
dedicates that unclaimed subject matter to the public.” Johnson, 285 F. 3d at 1054. “[T]he public
notice function of patents suggests that before unclaimed subject matter is deemed to have been
dedicated to the public, that unclaimed subject matter must have been identified by the patentee as
an alternative to a claim limitation.” Pfizer Inc. v. Teva Pharmaceuticals, USA, Inc., 429 F.3d
1364 (Fed. Cir. 2005). Generic references in a written specification do not necessarily dedicate all
members of a particular genus to the public. SanDisk Corp. v. Kingston Technology Co., Inc., 695
F.3d 1348, 1363 (Fed. Cir. 2012).
Rather, the ‘disclosure must be of such specificity that one of ordinary skill in the
art could identify the subject matter that had been disclosed and not claimed.’
Additionally, in Pfizer Inc. v. Teva Pharmaceuticals, USA, Inc., 429 F.3d 1364
(Fed. Cir. 2005), this court further clarified that ‘before unclaimed subject matter
is deemed to have been dedicated to the public, that unclaimed subject matter must
have been identified by the patentee as an alternative to a claim limitation.’
Id. (citations omitted). It is undisputed that pemetrexed ditromethamine was not disclosed
specifically in the ‘209 Patent, rather Hospira’s disclosure-dedication argument hinges on Lilly’s
disclosure of “any antifolate”. (Filing No. 74-1 at 35.) Additionally, Lilly asserts that pemetrexed
ditromethamine is not an alternative to pemetrexed disodium, rather the two are the same
antifolates because the active moiety—pemetrexed—targets the same relevant enzymes as defined
in the ‘209 Patent specification and understood by a POSA. (Filing No. 79 at 32-33.) Because
pemetrexed ditromethamine was not disclosed and identified with specificity, the disclosurededication rule does not prevent Lilly from pursuing a doctrine of equivalents infringement theory
nor dedicated it to the public.
C.

Inducement and Contribution to Infringement
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Direct infringement occurs when one party makes, uses, offers to sell, sells, or imports each
element of a patented invention. 35 U.S.C. § 271(a). Additionally, a party can be held liable for
indirect infringement by actively inducing or contributing to direct infringement by others. 35
U.S.C. § 271(b), (c). “Inducement requires that the alleged infringer knowingly induced
infringement and possessed a specific intent to encourage another’s infringement.” AstraZeneca
LP v. Apotex, Inc., 633 F.3d 1042, 1056 (Fed. Cir. 2010). Courts have inferred intent to induce
infringement based on the contents of labels. Id. (holding circumstantial evidence may suffice to
prove specific intent to induce infringement). “The pertinent question is whether the proposed
label instructs users to perform the patented method. If so, the proposed label may provide
evidence of [] affirmative intent to induce infringement.” AstraZeneca, 633 F.3d at 1060.
Similarly, labels may also form the basis to infer intent under contributory infringement when they
instruct users to perform a patented method. See Eli Lilly & Co. v. Actavis Elizabeth LLC, 435 F.
App’x 917, 926 (Fed. Cir. 2011). In a Hatch-Waxman case such as this, infringement “is focused
on the product that is likely to be sold following FDA approval,” including the relevant knowledge
of the parties at the time the product is sold. See Abbott Laboratories v. TorPharm, Inc., 300 F.3d
1367, 1373 (Fed. Cir. 2002) (“This determination is based on consideration of all the relevant
evidence, including the ANDA filing, other materials submitted by the accused infringer to the
FDA, and other evidence provided by the parties.”).
Hospira concedes that its label directs the use of folic acid and vitamin B12 as set forth in
the ‘209 Patent claims. (Filing No. 79-3 at 16.) Additionally, Hospira also concedes that should
this Court find literal infringement of “pemetrexed disodium” or finds that there is no bar to
infringement under the doctrine of equivalents, then, as a matter of law, use (and sale) of Hospira’s
NDA products according to their labeling, would satisfy indirect infringement under both

11

inducement and contributory theories. Moreover, Hospira has not addressed indirect infringement
in its summary judgment brief. Because the Court has found Hospira’s product literally infringes
and that there is no bar to infringement under the doctrine of equivalents, summary judgment is
granted to Lilly as to Hospira’s inducement of and contribution to infringement of the ‘209 Patent.
IV. CONCLUSION
For the foregoing reasons, Hospira’s Motion for Summary Judgment of Non-Infringement
(Filing No. 73) is DENIED and Lilly’s Cross-Motion for Summary Judgment of Infringement
pursuant to literal infringement and doctrine of equivalents (Filing No. 78) is GRANTED.
SO ORDERED.
6/15/2018
Date: ______________

DISTRIBUTION:
Adam L. Perlman
WILLIAMS & CONNOLLY LLP
[e-mail]

David M. Krinsky
WILLIAMS & CONNOLLY, LLP
[e-mail]

Alec T. Swafford
WILLIAMS & CONNOLLY LLP
[e-mail]

Dov P. Grossman
WILLIAMS & CONNOLLY, LLP
[e-mail]

Andrew Lemens
WILLIAMS & CONNOLLY LLP
Email: [e-mail]

Anne N. DePrez
BARNES & THORNBURG LLP
(Indianapolis)
[e-mail]

Bruce Roger Genderson
WILLIAMS & CONNOLLY LLP
[e-mail]

Jan M. Carroll
BARNES & THORNBURG, LLP
(Indianapolis)
[e-mail]

Galina I. Fomenkova
WILLIAMS & CONNOLLY LLP
[e-mail]

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Bradford P. Lyerla
JENNER & BLOCK LLP
[e-mail]

Sara Tonnies Horton
JENNER & BLOCK LLP
[e-mail]

Sally F. Zweig
KATZ KORIN CUNNINGHAM, P.C.
[e-mail]

Yusuf Esat
JENNER & BLOCK LLP
[e-mail]

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