Amicus Curiae Brief — Hikma Pharmaceuticals USA Inc., et al., Petitioners v. Amarin Pharma, Inc., et al.
Supreme Court briefMar 27, 2026
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No. 24-889
IN THE
Supreme Court of the United States
____________________________
HIKMA PHARMACEUTICALS USA INC., et al.,
Petitioners,
v.
AMARIN PHARMA, INC., et al.,
Respondents.
____________________________
ON WRIT OF CERTIORARI TO
THE UNITED STATES COURT OF APPEALS
FOR THE FEDERAL CIRCUIT
____________________________
BRIEF FOR PHARMACEUTICAL RESEARCH
AND MANUFACTURERS OF AMERICA AND
BIOTECHNOLOGY INNOVATION
ORGANIZATION AS AMICI CURIAE IN
SUPPORT OF RESPONDENTS
____________________________
David E. Korn
PHARMACEUTICAL
RESEARCH AND
MANUFACTURERS OF
AMERICA
670 Maine Ave., SW
Washington, DC 20024
(202) 835-3400
Sarah E. Harrington
Counsel of Record
Michael N. Kennedy
Krista H. Carver
COVINGTON & BURLING LLP
850 Tenth Street, NW
Washington, DC 20001
(202) 662-6000
sharrington@cov.com
Counsel for Amici Curiae
Additional Counsel Listed on Inside Cover
Joseph B. Franklin
John T. Delacourt
BIOTECHNOLOGY
INNOVATION
ORGANIZATION
1201 New York Ave., NW
Washington, DC 20005
Charlotte S. Butash
COVINGTON & BURLING
LLP
30 Hudson Yards
New York, NY 10001
i
TABLE OF CONTENTS
Page
TABLE OF AUTHORITIES .................................... iii
INTEREST OF AMICI CURIAE ............................. iii
INTRODUCTION AND SUMMARY ........................ 3
ARGUMENT ............................................................. 5
I.
Petitioners Seek a Special Immunity for
Generic Drugs That Has No Basis in the
Hatch-Waxman Act. ........................................... 5
A. Congress Struck a Careful Balance
Between Permitting Generics to Enter
the Market and Encouraging the
Research and Development of
Additional Indications. ................................. 7
B. Petitioners Seek to Upset Congress’s
Balance, Grabbing More Benefits for
Generic Drugs and Imperiling
Valuable Multiple-Indication
Innovation. .................................................. 10
C. Petitioners Propose Bright-line
Immunity for Generic Drug
Manufacturers to Encourage
Infringing Use Through Their
Promotional Materials and Statements
to Investors. ................................................. 13
D. Embracing Petitioners’ Position Would
Leave Generic Manufacturers to
Effectively Be the Final Judges of
Their Own Carveouts. ................................. 16
ii
II. Immunizing Petitioners’ Infringing
Statements, Including in Claimed Skinny
Labeling, Would Disrupt Investment and
Discourage the Discovery of New Uses for
Existing Drugs. ................................................. 20
A. Incentivizing Innovation Beyond FirstApproved Indications Promotes Public
Health. ......................................................... 22
1. Post-Approval Research and
Development Is a Vital Source of
New, Improved Treatment Options. ..... 22
2. Novel Indications May Prove Even
More Consequential Than the First...... 28
3. Post-Approval Research Has Led to
New Treatments for Rare Diseases
with Unmet Medical Need..................... 30
4. Investing in Additional Uses Can
Have Significant Benefits. ..................... 32
B. Drug Innovation Requires Massive
Investments in Post-Approval
Research That Will Be Inhibited If
Generic Manufacturers Are Permitted
to Infringe Patented Uses. .......................... 33
CONCLUSION ........................................................ 36
iii
TABLE OF AUTHORITIES
Page(s)
Cases
Amarin Pharma, Inc. v. Hikma Pharms.
USA Inc.,
104 F.4th 1370 (Fed. Cir. 2024) ....................... 29
Amarin Pharma, Inc. v. Hikma Pharms.
USA Inc.,
449 F. Supp. 3d 967 (D. Nev. 2020).................. 29
Amarin Pharma, Inc. v. Hikma Pharms.
USA Inc.,
819 F. App’x 932 (Fed. Cir. 2020) ..................... 29
Bell Atl. Corp. v. Twombly,
550 U.S. 544 (2007) ........................................... 10
Broadcom Corp. v. Qualcomm Inc.,
543 F.3d 683 (Fed. Cir. 2008) ........................... 15
Caraco Pharm. Lab’ys, Ltd. v. Novo Nordisk
A/S,
566 U.S. 399 (2012) ........................................... 18
Cox Commc’ns, Inc. v. Sony Music Ent.,
607 U.S. __, 2026 WL 815823 (2026) ........... 9, 10
GlaxoSmithKline LLC v. Teva Pharms.
USA, Inc.,
7 F.4th 1320 (Fed. Cir. 2021) ........................... 18
iv
Lucent Techs., Inc. v. Gateway, Inc.,
580 F.3d 1301 (Fed. Cir. 2009) ......................... 15
Roche Prod., Inc. v. Bolar Pharm. Co.,
733 F.2d 858 (Fed. Cir. 1984) ........................... 15
Statutes
21 U.S.C.
§ 355(j) ................................................................. 7
§ 355(j)(2)(A)(vii) ................................................. 8
§ 355(j)(2)(A)(viii) ................................ 7, 9, 10, 19
§ 355(j)(2)(B).................................................. 8, 19
§ 355(j)(5)(B)(ii) ................................................... 8
§ 355(j)(5)(B)(iv) .................................................. 8
§ 355(j)(5)(F)(ii) ................................................... 8
35 U.S.C.
§ 271(b) ................................................................ 9
§ 271(e)(1) ...................................................... 8, 15
§ 156..................................................................... 8
Regulatory Materials
21 C.F.R. § 314.94 .................................................... 9
Applications for FDA Approval to Market a
New Drug,
68 Fed. Reg. 36,676 (June 18, 2003) ................ 19
Abbreviated New Drug Applications and
505(b)(2) Applications,
81 Fed. Reg. 69,580 (Oct. 6, 2016) .................... 18
v
Legislative Materials
H.R. Rep. No. 98-857, pt. 1 (1984) ..................... 8, 15
Other Authorities
Ali Abbasi, Donna Rivera, Lesley H. Curtis
& Robert M. Califf, Post-Approval
Evidence Generation: A Shared
Responsibility for Healthcare, 30 Nature
Med. 3046 (2024)......................................... 32, 33
Amarin, Vascepa: Benefits, Clinical Trial
Results (2024) .................................................... 29
David Crosby et al., Early Detection of
Cancer, 375 Sci. 1244 (2022) ............................ 25
Joseph A. DiMasi, Henry G. Grabowski &
Ronald W. Hansen, Innovation in the
Pharmaceutical Industry: New
Estimates of R&D Costs, 47 J. Health
Econ. 20 (2016) .................................................. 34
Empl. Benefit Rsch. Inst., What Employers
Should Know About the Inflation
Reduction Act and Drug Development
(May 1, 2025) .................................................... 23
FDA, 40th Anniversary of the Generic Drug
Approval Pathway (Sep. 23, 2024) ............... 6, 11
FDA, FDA approves crizotininib for ALKpositive inflammatory myofibroblastic
tumor (July 14, 2022)........................................ 25
vi
FDA, FDA approves new treatment for
certain advanced or metastatic breast
cancers (Sept. 28, 2017) .................................... 26
FDA, New Drug Therapy Approvals (Jan.
2023) ...................................................... 29, 30, 31
FDA, Rare Disease Innovation Hub (Feb. 2,
2026) .................................................................. 30
Lawrence M. Fisher, Interferon Set to Treat
Hepatitis, N.Y. Times (Feb. 26, 1991) .............. 30
Henry Grabowski & Genia Long, PostApproval Indications and Clinical Trials
for Cardiovascular Drugs: Some
Implications of the US Inflation
Reduction Act, 27 J. Med. Econ. 463
(2024) ................................................................. 23
Henry Grabowski, Joseph A. DiMasi &
Genia Long, Postapproval Innovation for
Oncology Drugs and the Inflation
Reduction Act, 43 Health Affs. 1400
(2024) ................................................................. 23
IQVIA Inst., Global Oncology Trends 2022
(May 26, 2022) .................................................. 25
IQVIA Inst., Proliferation of Innovation
Over Time (Feb. 18, 2025) ................................ 31
Stephen Johnston et al., Overall Survival
with Abemaciclib in Early Breast
Cancer, 37 Annals Oncol. 156 (2026) ............... 26
vii
Lilly Investors, FDA Approves Verzenio®
(abemaciclib) as the First and Only
CDK4/6 Inhibitor for Certain People
with HR+ HER2- High Risk Early
Breast Cancer (Oct. 13, 2021) ........................... 26
Margret Merino et al., Irreconcilable
Differences: The Divorce Between
Response Rates, Progression-Free
Survival, and Overall Survival, 41 J.
Clin. Oncol. 2706 (2023) ................................... 27
Daniel Tobias Michaeli et al., Initial and
Supplementary Indication Approval of
New Targeted Cancer Drugs by the FDA,
EMA, Health Canada, and TGA, 40
Investigational New Drugs 798 (2022) ...... 24, 25
Kathleen L. Miller & Michael Lanthier,
Orphan Drug Label Expansions:
Analysis of Subsequent Rare and
Common Indication Approvals, 43
Health Affs. 18 (2024) ....................................... 31
P’ship for Health Analytic Rsch.,
Implications of the Inflation Reduction
Act Price Setting Provisions on Postapproval Indications for Small Molecule
Medicines (June 2023) ...................................... 22
Pfizer, Pfizer’s XALKORI® (crizotinib)
Approved by FDA for ALK positive
Anaplastic Large Cell Lymphoma in
Children and Young Adults, (Jan. 14,
2021) .................................................................. 25
viii
Pfizer, U.S. Food and Drug Administration
Approves Pfizer’s XALKORI® (crizotinib)
As First and Only Therapy Specifically
for Patients with Locally Advanced or
Metastatic ALK-Positive Non-Small Cell
Lung Cancer (Aug. 26, 2011) ............................ 24
PhRMA, Emerging Value Report (July
2023) .................................................................. 24
PhRMA, What is Hatch-Waxman? (June
2018) .................................................................. 11
Deborah Plana, Adam C. Palmer & Peter K.
Sorger, Independent Drug Action in
Combination Therapy: Implications for
Precision Oncology, 12 Cancer Discov.
606 (2022) .................................................... 26, 27
Benjamin N. Roin, Solving the Problem of
New Uses (Oct. 1, 2013) .................................... 21
Aylin Sertkaya, Trinidad Beleche, Amber
Jessup & Benjamin D. Sommers, Costs
of Drug Development and Research and
Development Intensity in the US, 20002018, 7 JAMA Network Open 1 (2024) ............ 33
Rajni Sethi & Nicholas Sanfilippo, SixMonth Depot Formulation of Leuprorelin
Acetate in the Treatment of Prostate
Cancer, 4 Clinical Interventions Aging
259 (2009) .......................................................... 31
Jesse C. Vivian, Generic Substitution Laws,
33 U.S. Pharmacist 30 (2008)........................... 12
1
INTEREST OF AMICI CURIAE1
The Pharmaceutical Research and Manufacturers
of America (PhRMA) represents the country’s leading
innovative biopharmaceutical research companies,
which are focused on developing innovative medicines
that transform lives and create a healthier world. Together, PhRMA’s member companies are fighting for
solutions to ensure patients can access and afford
medicines that prevent, treat, and cure disease.
PhRMA member companies have invested more than
$850 billion in the search for new treatments and
cures over the last decade, supporting nearly five million jobs in the United States.
Biotechnology Innovation Organization (BIO) is
the premier biotechnology advocacy organization representing biotech companies, industry leaders, and
state biotech associations in the United States and
more than 35 countries around the globe. BIO members range from biotech start-ups to some of the
world’s largest biopharmaceutical companies—all
united by the same goal: to develop medical and scientific breakthroughs that prevent and fight disease,
restore health, and improve patients’ lives. Many of
BIO’s members are small companies that have yet to
bring products to market or to attain profitability.
These members rely heavily on venture capital and
1 No counsel for a party authored this brief in whole or in part.
No party, counsel for a party, or any person other than amici and
their counsel made a monetary contribution intended to fund the
preparation or submission of this brief.
2
other private investment, based on and protected by
strong intellectual property rights.
Amici’s members share a significant interest in
the proper application of the framework Congress established in the Hatch-Waxman Act, 21 U.S.C.
§§ 355, et seq., which strikes a careful balance between permitting generic drugs to enter the market
and promoting ongoing investment in much-needed
post-approval research of approved, innovative medicines. Although amici’s members recognize that a return on their substantial investments in
pharmaceutical research and innovation is never
guaranteed, the meaningful protections found in the
U.S. patent system for both initial and subsequently
approved drug indications justify those investments
and encourage the cutting-edge drug innovation at
the heart of this country’s pharmaceutical industry.
3
INTRODUCTION AND SUMMARY
Research and clinical trials following a drug’s
initial approval are vital for medical progress, drug
innovation, and public health. After a drug’s initial
approval by the Food and Drug Administration
(FDA), it is not unusual for the drug’s manufacturer
to invest hundreds of millions of dollars to investigate
and develop additional uses for that drug. Resulting
FDA-approved indications provide new or improved
treatment options for a variety of diseases and conditions, including hard-to-treat and rare diseases. And
these medical advancements require massive investments—multi-year clinical programs and expensive
outcomes trials that often exceed the effort behind the
clinical program for the first approved use.
I. The Hatch-Waxman Act, 21 U.S.C. §§ 355, et
seq., represented Congress’s solution to balancing its
desire to expedite market entry for generic drugs with
the need to preserve incentives for drug innovation,
including in new uses of approved drugs. The Act does
so by establishing an abbreviated FDA approval process that allows generic manufacturers to sell their
products for unpatented uses. At the same time, the
Act maintains meaningful protections for patented indications. This balance encourages the search for new
drug indications through scientifically rigorous research and development after initial approval, while
permitting generic manufacturers to enter the market where their generic drugs are labeled and promoted only for unpatented indications.
The Federal Circuit’s decision in this case permitting Respondents’ patent infringement inducement
4
suit to proceed past the motion-to-dismiss stage is a
faithful implementation of that settled regulatory regime and long-established patent law. In asking this
Court to affirm that decision, Respondents seek only
the chance to prove their allegations that Petitioners
induced infringement of Respondents’ patent. Respondents do not seek special rules or expanded patent rights. They seek only application of ordinary
inducement principles, under which courts—not generic manufacturers—determine whether conduct
unlawfully encourages patented uses.
Petitioners in contrast ask this Court to upend
Congress’s careful design and award them a special
immunity from inducement liability not afforded to
companies in any other sector. But the bright-line, generic drug-specific immunity that Petitioners seek in
the name of improving access to medicines for patients would actually result in a contrary outcome. It
would erode drug innovation incentives, chill post-approval research, and ultimately deprive patients of
new treatments—backed by clinical trials demonstrating each use’s safety and efficacy—that will improve their lives. This Court should reject Petitioners’
invitation to accord them special treatment. It should
instead honor Congress’s weighing of interests in the
Hatch-Waxman Act and protect the ability of this
country’s pharmaceutical companies to develop innovative and transformative new treatments for patients who need them most.
II. The drug innovation at the core of this case is
essential to public health. Medical progress depends
on costly investment in research and development, including investments to study existing medicines for
5
potential new uses. That post-approval research has
delivered important new treatments for hard-to-treat
and rare diseases, and the benefits of some of these
new uses have dwarfed the benefits of the original indication several times over. But medical breakthroughs take time, and they take money. Ruling in
favor of Petitioners will undercut the incentives that
drive innovation, and when innovation falters, American patients waiting on new pharmaceutical treatments suffer.
ARGUMENT
I.
Petitioners Seek a Special Immunity for
Generic Drugs That Has No Basis in the
Hatch-Waxman Act.
Over forty years ago, Congress enacted the Drug
Price Competition and Patent Term Restoration Act,
better known as the Hatch-Waxman Act, 21 U.S.C.
§§ 355, et seq., to streamline the process for approving
generic drugs while preserving incentives for innovation. On one side of the ledger, Congress created a
new path for generic manufacturers to bring their
drugs to market through an abbreviated pathway.
One part of this pathway allows generic companies to
seek approval only for non-patented uses of the innovator drug while “carving out” a patented use. On the
other side of the ledger, Congress provided incentives
to ensure that pharmaceutical companies would continue researching and developing new, innovative
medicines—including new uses of approved drugs—
by, among other things, preserving patent protection
for such new uses and maintaining the applicability
6
of the Patent Act for any patent issues not resolved
before a generic launch.
That balance has proven remarkably effective at
achieving Congress’s goals. Before Hatch-Waxman,
only 19% of prescriptions were filled with generics.
Now, that number is 90%. See FDA, 40th Anniversary
of the Generic Drug Approval Pathway (Sep. 23,
2024).2 At the same time, innovative pharmaceutical
companies have continued to drive the development
of revolutionary new treatments, including discovering new uses for existing medications, such as treatments for chronic, complex, and rare diseases.
Yet Petitioners seemingly believe that Congress
should have given them more than this fair balance.
Petitioners argue that, as long as a “skinny” label
avoids reciting the relevant claim language, the
skinny label is non-inducing as a matter of law, and
infringement allegations directed against that label
must be dismissed at the pleading stage, regardless of
what other statements the generic manufacturer
makes about its product. The practical effect of Petitioners’ standard would be that a skinny label could
be deemed non-inducing as a matter of law regardless
of any other allegations showing inducement in a particular case, and generic manufacturers would be
granted license to make public statements about the
patented use without risk of inducement liability.
Petitioners thus seek to upset the careful balance
Congress created in Hatch-Waxman. They ask for a
2
https://www.fda.gov/drugs/cder-conversations/40th-anniversary-generic-drug-approval-pathway.
7
one-of-a-kind immunity from inducement liability, allowing generic manufacturers to promote the carvedout patented use in addition to the non-patented use
approved by FDA, as long as certain magic words are
not in their label. That is not the law. In Hatch-Waxman, Congress did not create special inducement
rules for generic drugs. Instead, generic manufacturers are, and should be, subject to the same inducement liability as companies in all other industries.
Congress certainly did not give generic manufacturers unreviewable discretion to decide for themselves
whether their labeling statements constitute unlawful inducement. Nor did it allow them to make public
statements concerning the patented use with impunity. Granting generic drug manufacturers these benefits would sharply depart from the careful
framework Congress established in the Hatch-Waxman Act and make it more difficult for pharmaceutical companies to drive innovation.
A. Congress Struck a Careful Balance
Between Permitting Generics to Enter
the Market and Encouraging the
Research
and
Development
of
Additional Indications.
To expedite generic drugs’ path to market, Congress bestowed several advantages on generic manufacturers in the Hatch-Waxman Act. As relevant to
this case, Congress created a statutory pathway allowing generics to come to market for non-protected
uses while “carving out” protected uses from their labeling. See 21 U.S.C. § 355(j)(2)(A)(viii). It also allowed generics to obtain FDA approval based on the
innovator manufacturer’s approval, see 21 U.S.C.
8
§ 355(j), established a 180-day market exclusivity period for certain generic drugs, see id. § 355(j)(5)(B)(iv),
and exempted generics from patent infringement liability for certain development work, see 35 U.S.C.
§ 271(e)(1).
Recognizing the risk that encouraging expansion
of the generic drug market might stifle drug development innovation, Congress at the same time provided
pharmaceutical companies with incentives for innovation. It granted innovator companies statutory exclusivities for eligible innovator drugs and permitted
innovators to seek to restore some of the patent term
lost due to the FDA approval process. See 21 U.S.C.
§ 355(j)(5)(F)(ii); 35 U.S.C. § 156. It generally required generic applicants to certify to innovator patents and provide notice of challenges to those
patents, and it gave the innovator the opportunity to
file an infringement suit to defend its patents against
a challenge before a generic launch. 21 U.S.C.
§§ 355(j)(2)(A)(vii), 355(j)(2)(B), 355(j)(5)(B)(ii).
And, critically, Congress maintained patent protections for method-of-use patents that remain in effect even if another indication for a drug is not
patented. In designing its framework, Congress specifically contemplated situations in which a “listed
drug may be approved for two indications.” H.R. Rep.
No. 98-857(I), at 22 (1984). In those situations, “[i]f
the [generic] applicant is seeking approval only for indication No. 1, and not indication No. 2 because it is
protected by a use patent, then the applicant must
make the appropriate certification and a statement
explaining that it is not seeking approval for indication No. 2.” Id. Even the government concedes here
9
that this “availability of method-of-use patents provides an important incentive for continued research
to identify additional therapeutic uses of established
drugs.” Br. for U.S. as Amicus Curiae Supp. Pet’rs 31
(filed Feb. 25, 2026) (U.S. Br.).
In other words, Congress allowed generic companies to obtain FDA approval of their drugs for off-patent uses and to market for only those uses. To obtain
approval for so-called “skinny labeling” covering only
unpatented uses of a drug, a generic manufacturer
files a “Section viii” statement with the FDA as part
of its abbreviated new drug application attesting that
the indication for which the applicant is seeking approval is not a patented method of use. 21 U.S.C.
§ 355(j)(2)(A)(viii). The applicant must also submit its
proposed labeling to the FDA omitting or carving out
all methods of use claimed in a patent. 21 C.F.R.
§ 314.94(a)(8)(iv).
But Section viii is not about liability. Congress
created a specific application requirement as an alternative to patent certification; it did not exempt filers
from the Patent Act or any other law. Thus, the abbreviated FDA drug approval in no way diminishes
patent protection over any patented method of use. As
a result, generic manufacturers may be liable for patent infringement if they encourage use of their product for a patented use—whether in their labeling
itself or in other statements, or both. See 35 U.S.C.
§ 271(b) (“Whoever actively induces infringement of a
patent shall be liable as an infringer.”).3 And a suit
3 This Court recently looked to Section 271(b) when analyzing
contributory liability under copyright law. See Cox Commc’ns,
10
against a generic manufacturer may therefore proceed beyond a motion to dismiss so long as the complaint provides “enough facts to state” an inducement
claim “that is plausible on its face.” Bell Atl. Corp. v.
Twombly, 550 U.S. 544, 570 (2007). Nothing in the
Hatch-Waxman Act, the Patent Act, or general pleading standards suggests that the Section viii pathway
constitutes a get-out-of-jail-free card for inducement
liability. Indeed, the provision discussing Section viii
statements simply requires generic applicants to include in their applications “a statement that the
method of use patent does not claim” “a use for which
the applicant is seeking approval.” 21 U.S.C.
§ 355(j)(2)(A)(viii). It says nothing about this statement somehow relieving the applicant of inducement
liability.
B. Petitioners Seek to Upset Congress’s
Balance, Grabbing More Benefits for
Generic Drugs and Imperiling Valuable
Multiple-Indication Innovation.
In keeping with the Hatch-Waxman Act’s structure, Petitioners received FDA approval only for generic icosapent ethyl’s unpatented use. That approval
was conditioned on Petitioners marketing the generic
drug only for the unpatented indication. Petitioners
Inc. v. Sony Music Ent., 607 U.S. __, 2026 WL 815823, at *3
(2026). In that case, the plaintiff “provided no evidence of express
promotion, marketing, and intent to promote infringement. And
[the defendant] repeatedly discouraged copyright infringement
by sending warnings, suspending services, and terminating accounts.” Id. at *7. In contrast, here, Respondents pointed to specific statements and promotional activities in alleging induced
infringement on the part of Petitioners.
11
now seek more than they are due under the Act—not
just sales and promotion of their generic for the unpatented use, but immunity to promote the patented
use, too.
It is important to emphasize what this case is not
about. The Federal Circuit’s decision did not cut back
in any way on Petitioners’ ability to sell their drug for
the unpatented use. The Federal Circuit’s decision
merely recognizes that generic drug manufacturers
may not use their labels, promotional materials, and
public statements to promote a patented use. That Respondents are not attempting to stamp out use of the
generic icosapent ethyl for non-patented uses is underscored by the fact that they have sued only one generic manufacturer for engaging in promotional
activities that encourage use of icosapent ethyl for its
patented use.
Nor is there any crisis in generic manufacturing
requiring this Court’s intervention. The Hatch-Waxman Act skyrocketed generic uptake in the United
States—from 19% of prescriptions to 90%. See 40th
Anniversary of the Generic Drug Approval Pathway,
supra. Other metrics reinforce the prevalence of generics. For example, more than 80% of approved medications have generic versions available on the
market, up from only 35% in the time before HatchWaxman. See PhRMA, What is Hatch-Waxman?
(June 2018).4 And generics often enter the market immediately upon patent expiration and are adopted
rapidly—some capture as much as 90% of the market
within three months. Id. Indeed, even when FDA
4 https://perma.cc/4Y3G-LHBM.
12
approves a generic drug only for non-patented indications, it has long been the case that generic products
are nevertheless used for patented indications
through automatic substitution of generics for the
listed drug, providing generic manufacturers with
even more market penetration. See Jesse C. Vivian,
Generic Substitution Laws, 33 U.S. Pharmacist 30
(2008) (describing automatic substitution for generic
drugs).5 Even though automatic substitution occurs,
pharmaceutical companies are able to pursue innovation because of the protections for new uses.
In short, the Hatch-Waxman Act has succeeded in
achieving Congress’s goals: the United States has a
robust generic drug market, and drug innovation continues. The Federal Circuit’s decision in this case
broke no new ground; the government’s concern that
“[u]ncertainty about [S]ection viii will deter generic
manufacturers from invoking that mechanism” is
therefore entirely misplaced. U.S. Br. 20.
There is thus no cause to contort either patent law
or pleading standards to provide generic manufactures like Petitioners with additional market advantages beyond those fairly afforded by Congress.
Indeed, although Petitioners contend their alleged
statements do not amount to patent inducement, they
fail to explain why they made the statements they
did—preplanned and considered statements like
press releases—if not to encourage use beyond the unpatented indication. Petitioners will have an opportunity at trial to convince a jury that they did not have
5 https://perma.cc/D9BQ-6LUF.
13
the requisite intent to induce infringement; this case
is solely about the adequacy of the pleadings.
C. Petitioners
Propose
Bright-line
Immunity
for
Generic
Drug
Manufacturers to Encourage Infringing
Use
Through
Their
Promotional
Materials and Statements to Investors.
In attempting to obtain more from the HatchWaxman Act than that scheme provides, Petitioners
seek to turn Section viii into an immunity provision.
They ask this Court to bless an approach that would
in effect provide a safe harbor for generic manufacturers to promote their drugs for patented uses in public
statements, so long as they do not expressly urge prescribers and patients to use the drug.
But that is not the statute that Congress enacted.
The skinny-labeling provisions of Hatch-Waxman
were never intended to provide generic manufacturers carte blanche to encourage using their drugs for
patented indications. The congressional scheme for
abbreviated FDA approval has always had as its
counterbalance the legal prohibitions on patent infringement and inducement of such infringement,
preserving for patentees their remedies under law to
address infringement.
This Court should reject Petitioners’ call for a
bright-line rule that general statements cannot induce infringement and must be considered in isolation.
Respondents
allege
that
Petitioners
intentionally induced infringement through their label in combination with statements in press releases
14
and on their website—including touting sales figures
largely attributable to the patented indication and
calling the product the “generic version” of a drug that
is indicated “in part” for the unpatented indication.
See, e.g., JA42–43. Petitioners argue in contrast
that—as a categorical rule—a case must be thrown
out on a motion to dismiss if the generic manufacturer’s communications do not each recite all the patent claim language or expressly encourage patients
and prescribers to use the drug for the patented uses.
Ruling that a party is, as a matter of law, not liable for induced infringement unless it uses the claim
language verbatim would fundamentally change inducement law across the board. Were Petitioners’
pleading standard adopted, a generic manufacturer
defendant could easily avoid liability for patent infringement by couching its references to patented
uses in more general language, even though its intended audience would readily recognize what is being conveyed. Indeed, Petitioners here chose to rely on
the language of a “generic version of Vascepa”—Respondents’ trademark that uniquely identifies their
product and indications—and chose to make references to the sales figures associated with Vascepa. If,
however, patent infringement defendants know that
courts will consider the full context of their public
statements, they have less incentive to craft
“wink-and-nod” messages designed to spur infringing
uses while staying just shy of an explicit instruction.
The immunity Petitioners seek would also make
generics the only actors in any patent-heavy industry
that are insulated from inducement liability. Manufacturers of software, telecommunications equipment,
15
and the like remain bound by the standard rules governing the encouragement of infringing conduct.
Those industries benefit from no safe harbors from infringement liability; in each, a court, looking at the
totality of allegations, considers whether the plaintiff
has stated an inducement claim. See, e.g., Lucent
Techs., Inc. v. Gateway, Inc., 580 F.3d 1301, 1322
(Fed. Cir. 2009) (regarding software products, “[a]
plaintiff may still prove the intent element [of induced
infringement] through circumstantial evidence”);
Broadcom Corp. v. Qualcomm Inc., 543 F.3d 683, 700
(Fed. Cir. 2008) (regarding wireless voice and data
communications patents, affirming a jury instruction
to consider “all of the circumstances” relevant to the
alleged induced infringement and concluding that
“[t]aken as a whole,” the record provided substantial
evidence to support the jury verdict).
Indeed, under Petitioners’ theory, innovator companies would lose their remedy for induced infringement of use patents, allowing generics to knowingly
profit from infringing uses. Congress expressly authorized only one safe harbor in Hatch-Waxman: the
safe harbor from infringement codified in 35 U.S.C.
§ 271(e)(1), which states that “[i]t shall not be an act
of infringement to make, use, offer to sell, or sell
within the United States or import into the United
States a patented invention . . . solely for uses reasonably related to the development and submission of information under a Federal law which regulates the
manufacture, use, or sale of drugs or veterinary biological products.” This provision overruled Roche
Product, Inc. v. Bolar Pharmaceutical Co., 733 F.2d
858 (Fed. Cir. 1984)), and created a safe harbor for
such development and submission activities. See H.R.
16
Rep. No. 98-857(I) (1984). Section 271(e)(1) demonstrates that when Congress meant to enact a safe harbor in this context, it expressly did so. Yet Congress
did not enact a safe harbor in the context of inducement liability for skinny labels. Generic manufacturers’ attempt to add a second safe harbor not
contemplated by Congress as part of the Hatch-Waxman compromise should be rejected.
Maintaining the balance struck by Congress is
particularly important in the biopharmaceutical industry, where the incentives to develop new, clinically
meaningful uses are fragile and the stakes for patients are profound. As explained in more detail, infra
Section II, the research necessary to bring a second
indication to market is long, expensive, and uncertain. Companies cannot justify investing millions of
dollars and years of effort only to be governed by a
regime where a generic competitor can promote the
patented use with impunity.
D. Embracing Petitioners’ Position Would
Leave
Generic
Manufacturers
to
Effectively Be the Final Judges of Their
Own Carveouts.
A decision from this Court holding that a pharmaceutical company plaintiff does not even state a claim
for induced patent infringement when it details multiple statements by the defendant referring to the infringing use gives generic manufactures an extrastatutory safe harbor, as explained supra Section I.C.
It also prevents judicial factfinders from determining
whether labels and promotional statements, considered together or taken separately, constitute unlawful
17
inducement. Without the policing of courts, generic
manufacturers would be free to decide—without oversight—that their labeling and marketing does not unlawfully encroach on patented uses.
The briefs of other parties are replete with statements asserting—or assuming—that Petitioners
drafted a properly skinny label. See, e.g., U.S. Br. 11
(“FDA approved Hikma’s ANDA, including its carvedout or ‘skinny’” labeling”); id at 26 (“Hikma’s skinny
labeling cannot properly be treated as evidence of culpable encouragement to infringe.”). These briefs elide
the fact that Respondents’ inducement allegations relied in significant part on Petitioners’ statements extrinsic to the label (as evidenced by the fact that
Respondents have not sued other generics who carved
out the patented indication). But the adequacy of Petitioners’ carveout is also a disputed factual question
in the case. Respondents asserted that Petitioners’ label encouraged use of the generic drug for the patented use. See Compl. ¶¶ 130–135, Amarin Pharma,
Inc. v. Hikma Pharms. USA Inc., 2021 WL 9316574
(D. Del. filed Jan. 25, 2021). If generic manufacturers
could self-certify that their labeling is properly
“skinny” without fear of inducement liability, they
would have unchecked discretion to discuss patented
uses in their labeling.
FDA’s review of the proposed skinny label is no
stand-in for judicial review. FDA does not police inducement; courts do. Rather, FDA’s role is a regulatory one—it determines whether the drug is the same
and bioequivalent to the listed drug for the requested
indication and whether the label accurately reflects
the non-patented approved use. FDA takes a Section
18
viii statement at face value. It does not evaluate
whether a proposed generic label infringes any patent, and FDA approval does not confirm that the label, or the marketing materials for the label, complies
with patent law. See GlaxoSmithKline LLC v. Teva
Pharms. USA, Inc., 7 F.4th 1320, 1332 (Fed. Cir.
2021) (“FDA plays no role in determining patent infringement”). When Petitioners suggest that FDA’s
acceptance of the Section viii carve-out somehow validates their position, they therefore misrepresent the
statutory scheme and FDA’s role within it.
Consistent with that statutory scheme, FDA has
made clear that its role in the approval process does
not remove the need for generic manufacturers to
evaluate their potential for liability under the patent
laws. As FDA has explained, the FDA “use code,” a
standardized descriptor that links a specific patent to
an FDA-approved method of using a drug, “is not intended to substitute for the . . . ANDA applicant’s review of the patent and the approved labeling.”
Abbreviated New Drug Applications and 505(b)(2)
Applications, 81 Fed. Reg. 69,580, 69,598 (Oct. 6,
2016); see also Caraco Pharm. Lab’ys, Ltd. v. Novo
Nordisk A/S, 566 U.S. 399, 403 (2012) (“[T]he FDA
requires brand manufacturers to submit descriptions
of the scope of their patents, known as use codes. The
FDA does not attempt to determine if that information is accurate.”); see U.S. Br. 7 (describing use
codes in FDA approval process). Any suggestion otherwise misconstrues the administrative function of
the tools at FDA’s disposal.
FDA’s role is limited, as it acknowledges. FDA
lacks the expertise, resources, and statutory
19
authority to review labeling or marketing materials
for generic products to ensure they avoid patent infringement by construing patent claims and adjudicating infringement issues. Indeed, FDA itself
observed that “[a] fundamental assumption of the
Hatch-Waxman Amendments is that the courts are
the appropriate mechanism for the resolution of disputes about the scope and validity of patents.”
Applications for FDA Approval to Market a New
Drug, 68 Fed. Reg. 36,676, 36,683 (June 18, 2003).
These legal questions are left with the courts because courts possess the expertise necessary to evaluate pharmaceutical patent infringement suits, just as
they do with respect to all other industries. Claim construction usually requires fact development and expert testimony. Whether a generic drug manufacturer
induced infringement through its label and promotional activities is a matter of patent enforcement.
That oversight is firmly within the purview of the federal judiciary. And this is especially important in the
Section viii context, which affords the patent holder
no other opportunity to weigh in on the proposed
skinny label; indeed, the patent holder does not even
receive advance notice of a generic’s skinny label.
Compare 21 U.S.C. § 355(j)(2)(B) (requiring notice to
the patent holder under a different mechanism under
the
Hatch-Waxman
Act)
with
21
U.S.C.
§ 355(j)(2)(A)(viii) (containing no notice requirement
for a Section viii statement).
As a final matter, amici curiae urge this Court—
whatever resolution it reaches in this particular
case—not to create a self-policed safe harbor for a selfdeclared skinny label and its marketing materials.
20
Even if the outcome in this case is favorable to Petitioners, the inquiry in future cases should remain
fact-specific and governed by an evaluation of the totality of the allegations in a particular complaint.
II. Immunizing
Petitioners’
Infringing
Statements, Including in Claimed Skinny
Labeling, Would Disrupt Investment and
Discourage the Discovery of New Uses for
Existing Drugs.
As explained, the Federal Circuit’s decision
should be upheld because it properly engaged with
the allegations in the complaint just as it would in any
other patent inducement suit and its ruling poses no
threat to the benefits provided to generic manufacturers under the Hatch-Waxman Act as properly understood. Overturning that decision, in contrast, would
impede American drug innovation and threaten potentially devastating consequences. Companies make
investment decisions in reliance on enforceable use
patents, and the investments are made with the understanding that the courts—not the generic competitors—will determine whether inducement has
occurred.
The biopharmaceutical industry, and the patients
it serves, depend on sustained investment in and continued pursuit of new drug therapies, in reliance on
enforceable use patents. This pursuit includes, but is
not limited to, new therapeutic uses for medicines already approved for a particular indication. Unlocking
additional indications has achieved significant medical breakthroughs in treating, for example, cancer
and rare diseases. At times, these transformative
21
treatment benefits have far exceeded the first approved use in terms of economic value to the innovator and therapeutic value to the patients. And that
work is far from over. Using screening technologies,
researchers have identified hundreds of drugs that
have the potential for additional indications. See Benjamin N. Roin, Solving the Problem of New Uses, at 42
(Oct. 1, 2013).6
But innovation does not come easily or cheaply. It
demands substantial post-approval investments in
scientific research and drug development—amounting to hundreds of millions of dollars and years of
study—undertaken amid significant uncertainty. Regardless of whether a new-indication patent issues,
automatic substitution will result in dispensing of generic versions to patients for all indications, including
the patented one, the moment a generic enters the
market. Under current law, those effects are partially
offset by the ability to pursue induced infringement
claims when a generic manufacturer actively promotes or knowingly facilitates infringing use through
its statements, labels, and marketing.
Permitting generic manufacturers to infringe
pharmaceutical patents on indications by encouraging use of generic drugs for patented uses would further
diminish
incentives
for
innovation.
Pharmaceutical companies strive to provide the best
medicines for American patients, but they are also
economic actors who must consider returns on investments as well as their duties to shareholders. Without
meaningful patent protection for additional
6 https://dx.doi.org/10.2139/ssrn.2337821.
22
indications for existing medicines, potential returns
are unlawfully limited and innovation will suffer,
harming patients in the process. Indeed, if pharmaceutical companies are deprived of any real mechanism to seek court review of whether a generic
manufacturer is inducing infringement of a patented
use, those companies will be forced to reevaluate their
investment decisions with respect to existing medications—and potentially even with respect to pre-approval innovation as well. They may choose not to
take on the risk and invest the time and money necessary to achieve the next breakthrough indication.
A. Incentivizing Innovation Beyond FirstApproved Indications Promotes Public
Health.
Innovative pharmaceutical companies often continue to study their products for additional indications after FDA approval. Discoveries emerging from
that research and investigation have reshaped standards of care, addressed serious unmet medical needs,
and delivered meaningful benefits to millions of patients.
1.
Post-Approval
Research
and
Development Is a Vital Source of
New, Improved Treatment Options.
Innovation after a first approval plays an indispensable role in advancing patient treatment. More
than half of small molecule medicines approved between 2006 and 2012 received FDA approval for at
least one additional post-approval new use. See P’ship
for Health Analytic Rsch., Implications of the
23
Inflation Reduction Act Price Setting Provisions on
Post-approval Indications for Small Molecule Medicines 2 (June 2023).7 Among cardiovascular medicines, for example, approximately half of all approved
uses and three-quarters of industry-funded clinical
trials occurred post-approval. See Henry Grabowski &
Genia Long, Post-Approval Indications and Clinical
Trials for Cardiovascular Drugs: Some Implications
of the US Inflation Reduction Act, 27 J. Med. Econ.
463, 466 (2024).8 And “small-molecule drugs used to
treat conditions related to oncology, cardiology, and
immunology” were prescribed to patients about twice
as often as they were prescribed for the initial indication. Empl. Benefit Rsch. Inst., What Employers
Should Know About the Inflation Reduction Act and
Drug Development 2 (May 1, 2025).9 About 35% of prescriptions were associated with the initial approval,
while 65% were associated with one of the medicine’s
subsequent indications. Id.
The evolution of new cancer therapies underscores just how essential post-approval research is to
advancing patient care. Post-approval research and
development is the main source of new cancer treatments—the majority of cancer research and development occurs after initial approval. For oncology drugs
approved from 2000 to 2021, more than half of all indications approved and approximately two-thirds of
industry-funded clinical trials occurred after the first
approval of the drug. Henry Grabowski, Joseph A.
7 https://perma.cc/UCY8-9A4U.
8 https://doi.org/10.1080/13696998.2024.2323903.
9 https://perma.cc/Q7XT-3USF.
24
DiMasi & Genia Long, Postapproval Innovation for
Oncology Drugs and the Inflation Reduction Act, 43
Health Affs. 1400, 1400 (2024).10
The importance of post-approval research and development is in part due to the nature of cancer, the
manner in which research on the value and benefits
of a medicine is conducted, and the way that scientific
evidence accumulates over time. See PhRMA, Emerging Value Report (July 2023).11
First, post-approval research and development often reveal shared features in different cancers, which
informs potential new uses of existing medicines. See
Daniel Tobias Michaeli et al., Initial and Supplementary Indication Approval of New Targeted Cancer
Drugs by the FDA, EMA, Health Canada, and TGA,
40 Investigational New Drugs 798, 798 (2022) (Initial
and supplementary indication approval).12 For example, in 2011, FDA granted accelerated approval to crizotinib to treat patients with locally advanced or
metastatic non-small cell lung cancer whose tumors
had an abnormality leading to cancer cell growth
caused by changes in a particular gene. See Pfizer,
U.S. Food and Drug Administration Approves Pfizer’s
XALKORI® (crizotinib) As First and Only Therapy
Specifically for Patients with Locally Advanced or
Metastatic ALK-Positive Non-Small Cell Lung Cancer
(Aug. 26, 2011).13 Similar changes in that gene then
10 https://doi.org/10.1377/hlthaff.2024.00202.
11 https://perma.cc/ARN3-6YTC.
12 https://doi.org/10.1007/s10637-022-01227-5.
13 https://perma.cc/YP62-TSKM.
25
were discovered in tumors across cancer types,
prompting researchers to study crizotinib’s untapped
potential. See Pfizer, Pfizer’s XALKORI® (crizotinib)
Approved by FDA for ALK positive Anaplastic Large
Cell Lymphoma in Children and Young Adults, (Jan.
14, 2021) (XALKORI Approved);14 see FDA, FDA approves crizotininib for ALK-positive inflammatory myofibroblastic tumor (July 14, 2022).15 That research
paid off. FDA has since greenlit multiple additional
indications—some coming a full decade after initial
approval—expanding treatment to adults and pediatric patients with rare cancer types. See XALKORI Approved, supra.
Second, researchers typically begin cancer research and development in narrowly defined patient
populations with advanced stages of cancer—those
who have exhausted all other treatment options. But
if that medicine proves to be safe and effective, researchers may seek to introduce the medicine to patients at earlier stages, where a new treatment is
more likely to significantly modify the course of the
disease and may even halt its progression. See generally IQVIA Inst., Global Oncology Trends 2022 (May
26, 2022);16 Initial and Supplementary Indication Approval, supra; David Crosby et al., Early Detection of
Cancer, 375 Sci. 1244, 1244 (2022).17 Abemaciclib, for
14 https://perma.cc/Z2L4-8NYL.
15
https://www.fda.gov/drugs/resources-information-approveddrugs/fda-approves-crizotinib-alk-positive-inflammatory-myofibroblastic-tumor.
16 https://doi.org/10.13140/RG.2.2.11901.06882.
17 https://doi.org/10.1126/science.aay9040.
26
example, was originally approved to treat advanced
or metastatic breast cancer that had progressed following hormone therapy. See FDA, FDA approves new
treatment for certain advanced or metastatic breast
cancers (Sept. 28, 2017) (republished in PR Newswire).18 After additional clinical research, it was later
approved to treat the most common subtype of early
breast cancer: HR+ HER2-. That approval marked the
first new treatment of its kind in nearly two decades,
and the first and only medicine in its class approved
for patients with that subtype. See Lilly Investors,
FDA Approves Verzenio® (abemaciclib) as the First
and Only CDK4/6 Inhibitor for Certain People with
HR+ HER2- High Risk Early Breast Cancer (Oct. 13,
2021).19 Recent data confirm that abemaciclib significantly improves overall survival in patients with this
type of early breast cancer, making it the first CDK4/6
inhibitor to demonstrate that reducing the risk of recurrence translates into improved overall survival,
and “mark[ing] [a] major milestone in the development of effective therapies that have the potential to
cure more patients with this common form of breast
cancer.” Stephen Johnston et al., Overall Survival
with Abemaciclib in Early Breast Cancer, 37 Annals
Oncol. 156, 162 (2026).20
Third, post-approval research and development
can lead to a greater understanding of the safety and
efficacy of combining multiple medicines as compared
to a single therapy. See Deborah Plana, Adam C.
18 https://perma.cc/H77M-9UUW.
19 https://perma.cc/W23L-ZZCJ.
20 https://doi.org/10.1016/j.annonc.2025.10.005.
27
Palmer & Peter K. Sorger, Independent Drug Action
in Combination Therapy: Implications for Precision
Oncology, 12 Cancer Discov. 606, 606–07 (2022).21
That benefit is particularly important for treating
cancers, where patients often need a combination of
treatments to attack the disease on multiple fronts
and prevent treatment resistance. A single drug
might not be effective in eradicating every cancer cell
in a tumor—it might target some, or even a majority,
of a certain type of cells but leave behind resistant
cells, which then repopulate the tumor. See id. at 607.
Drug combinations, in contrast, can target different
subsets of cells, which improves both the efficacy and
the durability of the treatment. See id. The same goes
for treatments across different patients: a single therapy will not be effective in every patient, but combination therapies provide patients with opportunities
for a clinically meaningful response. See id. Post-approval research is necessary to determine the availability of these combination treatments.
Finally, post-approval research and development
help shed light on the full therapeutic value of a particular cancer treatment. Overall survival is considered the “gold standard” for evidence of a cancer
drug’s safety and effectiveness, but it can take years
of follow up with patients to determine if a treatment
actually prolongs patients’ lives. Margret Merino et
al., Irreconcilable Differences: The Divorce Between
Response Rates, Progression-Free Survival, and Overall Survival, 41 J. Clin. Oncol. 2706, 2706 (2023).22 As
21 https://doi.org/10.1158/2159-8290.CD-21-0212.
22 https://doi.org/10.1200/JCO.23.00225.
28
a result, beneficial evidence of a treatment’s safety
and effectiveness can emerge years after a drug first
reaches the market, through continued investment in
post-approval research.
The long-term clinical development needed to discover these additional uses involves years of research,
significant risk, and substantial financial investment.
Without post-approval research and development—
and the necessary incentives to enable it—these medications would never have expanded beyond their
original uses.
2.
Novel Indications May Prove Even
More Consequential Than the First.
Post-approval research and development do not
just drive development within the same therapeutic
area; they have also resulted in transformative new
uses and treatments in different diseases, including
on a scale the original indication never approached.
New uses of approved medicines have provided critical treatment advances, particularly for cancer patients, children, and those impacted by rare diseases.
Many of these post-approval research advances
brought first-time treatments for patients.
Take Respondents’ product, Vascepa. Respondents seek to enforce their patent on a subsequent patented use approved by the FDA. Vascepa began as a
triglyceride-lowering therapy in patients with very
high triglycerides and has evolved into a major cardiovascular-risk-reduction drug. After obtaining approval on an initial indication that covered a limited
29
patient population,23 Amarin invested in a
“[l]andmark” trial that included over 8000 patients
and lasted nearly five years, see Amarin, Vascepa:
Benefits, Clinical Trial Results (2024).24 That trial revealed “groundbreaking” results showing that, when
used together with cholesterol medications known as
statins, Vascepa reduced cardiovascular events by
roughly 25%. Id. Those results far exceeded the clinical impact of the initial hypertriglyceridemia indication. And there had previously been no proven way to
reduce persistent cardiovascular risk for this population of cardiovascular patients with high triglycerides. Id. Vascepa became the first and only medication
approved by FDA for that purpose. Id.
Similar examples exist across therapeutic areas.
In 2022, FDA approved a new indication for an existing medicine that became the first approved therapy
targeted to “HER2-low” breast cancer—a form of
breast cancer that historically has had limited treatment options. See FDA, New Drug Therapy Approvals
23 See Amarin Pharma, Inc. v. Hikma Pharms. USA Inc., 449 F.
Supp. 3d 967, 983 (D. Nev.) (noting first indication trial included
only 151 patients), aff’d, 819 F. App’x 932 (Fed. Cir. 2020); see
also Amarin Pharma, Inc. v. Hikma Pharms. USA Inc., 104
F.4th 1370, 1374 (Fed. Cir. 2024) (“[T]he CV indication ... undisputedly made up more than 75% of the drug’s sales.”); Compl.
¶ 152, Amarin Pharma, Inc. v. Hikma Pharms. USA Inc., 2021
WL 9316574 (“Available market data indicates that less than
10% of the prescriptions of VASCEPA® are currently in the Severe Hypertriglyceridemia population and thus could be covered
under the Severe Hypertriglyceridemia Indication.”).
24 https://perma.cc/AQ8L-ZRTR.
30
(Jan. 2023).25 The same year, two treatments were
newly approved for use in combination to treat pediatric patients whose tumors express a BRAF mutation. See id. The list goes on. See id. (collecting notable
approvals for new uses or indications of approved
drugs).
And this is not a new phenomenon. In 1986, interferon was approved for hairy cell leukemia, a very
rare cancer. See Lawrence M. Fisher, Interferon Set to
Treat Hepatitis, N.Y. Times (Feb. 26, 1991). Five
years later, interferon was approved to treat hepatitis
C—a contagious disease for which there was no reliable therapy. See id. Interferon became the standard of
care in hepatitis C treatment for years.
3.
Post-Approval Research Has Led to
New Treatments for Rare Diseases
with Unmet Medical Need.
Discovering treatments for rare diseases is a top
public health priority. Rare diseases can be lifethreatening, and most do not have approved treatments. An estimated 10,000 rare diseases affect approximately one out of every ten Americans—more
than 30 million people. Half of those affected are children. See FDA, Rare Disease Innovation Hub (Feb. 2,
2026).26
https://www.fda.gov/drugs/novel-drug-approvals-fda/newdrug-therapy-approvals-2022.
25
26 https://www.fda.gov/industry/medical-products-rare-diseases-
and-conditions/fda-rare-disease-innovation-
31
Post-approval research and development are essential for advancing new treatments for rare diseases. Nearly 30% of all post-approval uses treat
patients with rare diseases. See IQVIA Inst., Proliferation of Innovation Over Time, at 14 (Feb. 18, 2025).27
And 35% of drugs for rare diseases—known as “orphan-designated” drugs—have a post-approval indication in a new disease. See Kathleen L. Miller &
Michael Lanthier, Orphan Drug Label Expansions:
Analysis of Subsequent Rare and Common Indication
Approvals, 43 Health Affs. 18, 20 (2024).28
To take some examples, the first approved treatment for symptoms of Bardet-Biedl syndrome, a rare
genetic disorder, emerged from an existing medicine.
See New Drug Therapy Approvals, supra. As did the
first approved treatment for pediatric patients with
juvenile myelomonocytic leukemia, a rare and aggressive blood cancer primarily affecting young children.
See id. And in 1985, leuprolide acetate was approved
as a palliative treatment for advanced prostate cancer; less than ten years later, it was approved to treat
central precocious puberty, a rare disease in children
under the age of nine. Rajni Sethi & Nicholas Sanfilippo, Six-Month Depot Formulation of Leuprorelin Acetate in the Treatment of Prostate Cancer, 4 Clinical
Interventions Aging 259, 261 (2009).29 Without the
sponsor’s investment in a second medical use,
hub#:~:text=An%20estimated%2010%2C000+%20rare%20diseases,and%20Office%20of%20Combination%20Products./.
27 https://perma.cc/BV7X-R3WU.
28 https://doi.org/10.1377/hlthaff.2023.00219.
29 https://doi.org/10.2147/cia.s4885.
32
treatment options for these rare diseases would not
exist, and patients would be deprived of potentially
life-saving medicines.
4.
Investing in Additional Uses Can
Have Significant Benefits.
Clinical trials for second indications provide authoritative evidence of safety and efficacy beyond the
research necessary to obtain an initial approval. This
in-depth clinical research creates confidence in a particular medication and ensures that it is safe and effective for patients for the new use. The alternative is
that the manufacturer never invests in a second indication, but doctors nevertheless prescribe the medication “off-label” without any (or insufficient) safety and
efficacy studies on that particular use.
Some of the most important insights into a drug’s
potential occur after approval; indeed, some questions
can be answered only after a drug is approved. See Ali
Abbasi, Donna Rivera, Lesley H. Curtis & Robert M.
Califf, Post-Approval Evidence Generation: A Shared
Responsibility for Healthcare, 30 Nature Med. 3046,
3047 (2024).30 Questions of comparative effectiveness,
for example, are rarely resolved at the time of approval because the standard of care is constantly
evolving and context specific; a comparator used in
pre-approval trials is not necessarily the alternative
option actively considered by doctors and patients after a drug reaches the market. Id. And continued research often sheds greater light on a drug’s safety,
30 https://doi.org/10.1038/s41591-024-03241-x.
33
especially given the length of time required for the
completion of some clinical trials. Id.
All of this reflects a simple but important reality:
protecting the exclusivity afforded by a grant of a patent—and therefore return on investment—of subsequent indications strengthens patient safety and
public health. It promotes the rigorous research and
clinical studies needed to understand a therapy’s full
clinical value and supports the evidence-backed treatments patients turn to most frequently.
B. Drug Innovation Requires Massive
Investments in Post-Approval Research
That Will Be Inhibited If Generic
Manufacturers
Are
Permitted
to
Infringe Patented Uses.
Securing a second indication is not simply an extension of the first; it often represents a new—and
sometimes even bigger—financial bet. Post-approval
development regularly requires massive investments,
multi-year clinical programs, and large outcome trials
designed to generate the evidence needed to affirm a
medicine’s safety and efficacy for a new purpose.
Novel indications can require large, expensive
outcome trials—especially for common conditions.
These trials deliver outsized population-health gains,
across safety, efficacy, and appropriate use. Most approvals of additional indications are supported by
Phase III trials. Based on trial data from both new
and existing molecules, some estimates put the cash
outlay for a Phase III clinical trial at $31.3 to $214.4
million across therapeutic areas. See Aylin Sertkaya,
34
Trinidad Beleche, Amber Jessup & Benjamin D. Sommers, Costs of Drug Development and Research and
Development Intensity in the US, 2000-2018, 7 JAMA
Network Open 1, 7 (2024) (using 2018 dollars).31 This
cost represents solely the expense of running a trial,
not incorporating the costs of failures. Other estimates set the mean total cash outlay for Phase III at
$255.4 million based on data from new molecules. See
Joseph A. DiMasi, Henry G. Grabowski & Ronald W.
Hansen, Innovation in the Pharmaceutical Industry:
New Estimates of R&D Costs, 47 J. Health Econ. 20,
24 (2016).32
As explained above, pharmaceutical companies
are able to make these substantial investments, even
in the face of meaningful scientific uncertainty, in reliance on their ability to protect against induced infringement. Companies understand that on the other
end of hundreds of millions of dollars and a decade or
more of research, the novel use that they discover can
be protected, even as generics enter the market.
Although in reality generic drugs are often dispensed as substitutes for the prescribed innovator
drug, under existing law generic manufacturers are
not immunized from infringement liability, and patent owners can address infringement through all the
tools provided in the Patent Act. Under Petitioners’
proposed rule, however, any generic that files a Section viii statement and has an allegedly skinny label
would be categorically immunized from inducement
31 https://doi.org/10.1001/jamanetworkopen.2024.15445.
32 https://doi.org/10.1016/j.jhealeco.2016.01.012.
35
liability, no matter how it encourages infringement
through its statements or marketing. Petitioners thus
seek to turn Section viii into an express immunity
ticket, effectively taking away remedies Congress
chose to make available to patent owners. Doing so
would amplify the effects of automatic substitution
and erode innovation incentives beyond the status
quo.
Pharmaceutical companies cannot rationally invest in developing new uses if, on the other side, they
will be denied the opportunity to obtain meaningful
judicial review of whether a generic manufacturer induced infringement. Petitioners’ position thus undermines the legal protections that are necessary for
pharmaceutical companies to justify continued investment in developing lifesaving new treatments.
***
Congress has already struck the balance between expediting generic drugs’ market entry and assuring patent protections for later-approved
indications. The Federal Circuit’s decision respected
that balance, applying generally applicable patent
and pleading principles to the case before it. Petitioners instead invite this Court to create a bright-line
safe harbor for infringing statements that has no statutory basis. The Court should decline the invitation;
regardless of how it rules on the facts of this case, the
Court should make clear that generic manufacturers
are subject to the same rules governing infringement
inducement as manufacturers in other industries.
36
CONCLUSION
The Federal Circuit’s decision should be affirmed.
Respectfully submitted,
David E. Korn
PHARMACEUTICAL
RESEARCH AND
MANUFACTURERS OF
AMERICA
670 Maine Ave., SW
Washington, DC 20024
(202) 835-3400
Sarah E. Harrington
Counsel of Record
Michael N. Kennedy
Krista H. Carver
COVINGTON & BURLING
LLP
850 Tenth Street, NW
Washington, DC 20001
(202) 662-6000
sharrington@cov.com
Joseph B. Franklin
John T. Delacourt
BIOTECHNOLOGY
INNOVATION
ORGANIZATION
1201 New York Ave., NW
Washington, DC 20005
Charlotte S. Butash
COVINGTON & BURLING
LLP
30 Hudson Yards
New York, NY 10001
March 27, 2026
This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.