THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1): THE COSTLY

CONFUSION ABOUT THE SCOPE OF “PATENTED INVENTION”

ABRAHAM PHILLIPS*

I. INTRODUCTION

A. The Problem to be Solved

A patent in the United States conveys an exclusive right over an invention for
a limited term,1 often about seventeen years.2 During this interval, the patent
holder has the right to stop others from making, using, selling, importing, or
offering to sell the claimed invention in the United States.3 This power to exclude
had a compounded effect for drug and medical device inventions requiring U.S.
Food and Drug Administration (“FDA”) approval prior to market entry. Stopping
a future competitor from using an FDA-regulated invention throughout the entire
patent term also prohibited the competitor from beginning the FDA approval
process until the patent expired. Quantitatively, this extended the legal monopoly
of the patent holder by between one-and-a-half to six years for the competitor’s
clinical trials alone.4

Meanwhile, the invention owner’s path to FDA approval for a regulated drug
or medical device was often not without a symmetric grievance. The patent holder
commonly obtained FDA approval long after their original patent filing date–the
date which started the clock on the twenty-year term. Accordingly, the inventor
waited several years for FDA approval to sell the regulated invention, thereby
shortening the effective patent term. Unsurprisingly, a patent holder’s enjoyment
of no competition while a generic sought FDA approval was often deemed
warranted by the patent holder’s own “regulatory entanglements” on the front end
of selling a patented drug.5 While this rationale may reek of the unsatisfying
fallacy that “two wrongs make a right,” it nevertheless prevailed during
legislative silence. Resolving this symmetric distortion is a subject courts and
legislatures have wrestled with for decades.

* J.D. Candidate, 2023, Indiana University– Robert H. McKinney School of Law; B.S.,

2013, University of Illinois, Urbana-Champaign.

1. 35 U.S.C. § 154(a)(2) (2013). The exact term of exclusionary rights over a patented

invention begins on the day the associated patent issues and terminates twenty years from its

earliest application’s filing date.

2. Id. The interval over which an inventor may enforce a patent is often around seventeen

years because patents often grant two to three years after their earliest filing date.

3. 35 U.S.C. § 154(a)(1) (2013).

4. Step 3: Clinical Research, U.S. FOOD & DRUG ADMIN., https://www.fda.gov/patients/

drug-development-process/step-3-clinical-research [https://perma.cc/Z76B-NZEL] (last updated

Jan. 4, 2018) (clinical trials are generally the longest phase of FDA approval).

5. Roche Products, Inc. v. Bolar Pharm. Co., 733 F.2d 858, 864 (Fed. Cir. 1984) (prior to

§156 of the Hatch-Waxman Act, the filing date started the patent term clock even though the drug

was not approved by the FDA and could not be sold).



144 INDIANA HEALTH LAW REVIEW [Vol. 20:143

B. Executive Summary

To understand current problems with the statutory solution to patent term
distortions arising from FDA approval, this Note begins with describing the
judicial tool most promising to resolve the most contentious distortion–an
“experimental use exemption” to patent infringement granted under certain
circumstances.6 After explaining how the experimental use exemption ultimately
failed to provide satisfactory results, the Note introduces the responsive
legislative solution–the Hatch-Waxman Act (“Act”).

The Note then assesses the language of the Act and unfolds the case law
developing its most litigated terms. After criticizing the Act’s use of undefined
statutory terms–which do not secure a preferable symmetry between
complementary Sections of the Act–the Note explains how courts now disagree,
at least in part, on the scope of what inventions are shielded from patent
infringement claims.

After suggesting a legislative amendment to the Act, the Note then focuses
on a certain class of inventions commonly known as research tools. These
inventions are not themselves subject to FDA approval–though they are
consistently used in obtaining FDA approval for other products. Research tools
are abundant in a laboratory and include at least mechanical, biochemical,
biological, and chemical articles. This Note exposes uncertainty in the status of
these tools under the Act and illustrates continued uncertainty after the judiciary’s
failed attempt to clarify. The Note also briefly assesses the general consequence
of this ambiguity.

The Note then illustrates the detrimental effect this uncertainty is having on
predictability of litigation by examining two cases, filed on the same day, in
different jurisdictions. The cases have materially equivalent facts–the same
plaintiff suing for patent infringement based on a similar use of the same patented
research tool. While one case has now settled, the jurisdictions still have
conflicting precedent on the precise issue which may prove dispositive in future
litigation.

The Note concludes by proposing the judiciary adopt a bright-line rule
excluding research tools from the purview of the Act’s safe harbor. Though
legislative action would be preferable, this Note maintains it is not required for
a clear interpretation of the statute. Importantly, the judiciary need not fear
entering the legislative realm to clarify the uncertainty–and it is in fact the
judiciary’s duty. Rather, for the judiciary to remain silent while a well-defined
industry is subject to unpredictable liability, arising from everyday business
decisions, may constitute a dereliction of duty.

C. From the Experimental Use Doctrine to a Statute

Sprouting from a germinate sentence written by Justice Story in 1813, the
common law exemption against patent infringement grew into the experimental

6. Moore U.S.A., Inc. v. Standard Reg., 144 F. Supp. 2d 188, 196 (W.D.N.Y. 2001).



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 145

use doctrine.7 Justice Story recognized a sort of honor in curiosity without
monetary gain and thought it was incompatible with the patent laws to punish a
purely inquisitive mind.8 With a subtle boldness, Story asserted “it could never
have been the intention of the legislature to punish a man, who constructed such
a machine merely for philosophical experiments, or for the purpose of
ascertaining the sufficiency of the machine to produce its described effects.”9 This
became known as the common law exemption to patent infringement. Forty-eight
years later this doctrine stated that an “experiment with a patented article for the
sole purpose of gratifying a philosophical taste, or curiosity, or for mere
amusement” is not patent infringement–considerably close to Justice Story’s own
description.10 In fact, the doctrine departed from its origins for over a century.

Gradually, in applying this doctrine, a distinction resulted in the emergence
of two branches of thought within cases. The broadest view maintained
experimental use defenses to patent infringement could be honored even when the
use was for business purposes–as long as the product was not sold or intended for
sale.11 The public policy rationale was to allow competitors to seek improvements
upon another’s invention without liability and, in theory, accelerate innovation.12

The narrower view held the experimental use exemption was to be forfeited as a
defense if the patented product was used “in keeping with a legitimate business
of the using agency.13 Thus, courts were divided on whether the experimental use
exemption could be used as a means of shielding oneself from liability while
actively advancing a business interest. In a fundamental sense, this conceptual
divide over public policy and the role of patents is still present today.

In 1984, the broader branch of case law invited a generic drug manufacturer
to offer the experimental use doctrine as a defense against patent infringement.14

In Roche Products v. Bolar Pharmaceuticals, the generic manufacturer used a
patented drug–prior to the patent’s expiration–in seeking its FDA approval.15

Bolar Pharmaceuticals had imported the patented substance to assess parameters
required by the FDA to prove bioequivalence, thus ensuring the generic version

7. Whittemore v. Cutter, 29 Fed. Cas. 1120, 1121 (C.C.D. Mass. 1813).

8. Id.

9. Id.

10. Poppenhusen v. Falke, 19 Fed. Cas. 1048, 1049 (C.C.S.D.N.Y. 1861).

11. See Chesterfield v. United States, 159 F. Supp. 371, 375 (Ct. Cl. 1958) (experimentation

with patented steel alloys excused under experimental use inter alia because no evidence suggested

the manufacture sold or intended it for sale); Dugan v. Lear Avia, 55 F. Supp. 223 (S.D.N.Y. 1944),

aff'd sub nom. Dugan v. Lear, Inc., 156 F.2d 29 (2d Cir. 1946) (building of a patented device was

protected from infringement because, though it was built by a business, it was not sold or intended

for sale); Akro Agate Co. v. Master Marble Co., 18 F. Supp. 305 (N.D.W. Va. 1937) (making and

using a patented product was protected from infringement because, though it was made and

confirmed to work with production equipment, it was not commercially sold).

12. Dugan v. Lear Avia, 55 F. Supp. 223, 228 (S.D.N.Y. 1944).

13. Pitcairn v. United States, 547 F.2d 1106, 1125-26 (Ct. Cl. 1976).

14. Roche Products, Inc., 733 F.2d at 862.

15. Id. at 860.



146 INDIANA HEALTH LAW REVIEW [Vol. 20:143

would be market-ready soon after Roche’s patent expired.16 In an unusually
forceful opinion, the newly minted17 Federal Circuit declined to extend the
experimental use doctrine to protect generics seeking FDA approval, emphasizing
the doctrine was ill-fitted for the circumstances and that the Federal Circuit was
not authorized to rewrite patent law.18

Thus, while generic drug manufacturers once offered the experimental use
exemption with a flicker of hope that it might protect their pursuit of FDA
approval in advance of patent expiration, the Roche court formally snuffed out
exactly that wish. In its stated refusal to act in a legislative manner,19 the Roche
court deliberately highlighted the strong public policy rationale for an exemption.
The public welfare, in the form of affordable drug prices, depends on price
competition as much as protecting the right to profit from a large investment.20

Without the former, fewer can afford the drugs produced; without the latter, the
drugs may never be developed at all. Even so, the court noted the strength of any
public policy rationale as immaterial to their task–naming the legislature as the
proper forum for such a debate and referencing pending legislation on the very
issue.21 The Roche opinion has been interpreted as a “very narrow” experimental
use exemption.22 The often-quoted standard from Roche holds the exemption is
limited to actions performed “for amusement, to satisfy idle curiosity, or for
strictly philosophical inquiry”– a hermetically sealed version of the Poppenhusen
wording from the mid-nineteenth century.23

Within months of the Roche decision, the Drug Price Competition and Patent
Term Restoration Act (“the Act” or “the Hatch-Waxman Act”) was signed into
law in September of 1984.24 As designed, § 271(e)(1) of the Hatch-Waxman Act,

16. Id.

17. U.S. CT. OF APP. FOR THE FED. CIR., https://cafc.uscourts.gov/home/the-court/about-the-

court/ [ https://perma.cc/TU97-7D48] (last visited Dec. 17, 2022) (the Federal Circuit formed as

an Article III court on October 1, 1982, by the merging of the United States Court of Customs and

Patent Appeals and the appellate division of the United States Court of Claims).

18. Roche Products, Inc., 733 F.2d at 862-65 (the Federal Circuit flags the expansive view

of experimental use shielding “experiment” as “obiter dictum” and refuses to “rewrite the patent

laws”).

19. Id. at 863-64 (“Parties. . .seem to think. . .we must resolve a conflict between the Federal

Food, Drug, and Cosmetic Act. . .and the Patent Act[.] We decline the opportunity here, however,

to engage in legislative activity proper only for the Congress.”).

20. Id. at 865.

21. Id. (the Federal Circuit emphasized the fact Congress was actively debating the Drug

Price Competition Act of 1983).

22. Madey v. Duke University, 307 F.3d 1351, 1362 (Fed. Cir. 2002).

23. Roche Products, Inc., 733 F.2d at 863; see also Madey, 307 F.3d at 1362 (quoting

Embrex, Inc. v. Serv. Eng’g Corp., 216 F.3d 1343 (Fed. Cir. 2000)) (consistent reliance on Roche’s

language).

24. President's Remarks on Signing the Drug Price Competition and Patent Term Restoration

Act of 1984 at the White House, Washington D.C., 20 PUB. PAPERS 39 (Sept. 24, 1984) (Ronald

Reagan signed the Hatch-Waxman Act into law on September 24, 1984).



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 147

commonly referred to as the “safe harbor” provision, successfully allows a
generic drug manufacturer to use a patented drug prior to patent expiration when
generating data for FDA submission:

It 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.25

When construing the terms of the statute above, it is interesting to consider
the judicial interpretation of its sister statute – § 156, relating to extension of a
patent term–also part of the Hatch-Waxman Act.26 In addition to providing a
remedy for generics being delayed in market entry, the Hatch-Waxman legislation
also sought to remedy the symmetric distortion on the effective start date of a
patent term.27 As introduced above, the patent term would often begin before the
FDA had approved the drug for use–reducing the profitable term of the patent on
its front end.28 This reduction in profitable term was not only unpredictable, but
out of the inventor’s control while the data was with the FDA for review and
approval.

Under § 156 of the 1984 Hatch-Waxman legislation, an original drug
manufacture can receive a patent term extension if the patent term is triggered
prior to receiving regulatory approval.29 The exact extension is calculated
according to the statute.30 Importantly, this provision is codified using the term
“product,” to describe those items falling within its ambit.31 Indeed, the statute
explicitly defines “product” to refer to “[a]ny medical device, food additive, or
color additive subject to regulation under the Federal Food, Drug, and Cosmetic
Act.”32 In an unsuspected contrast, and despite the symmetry in function, §
271(e)(1) uses “patented invention” to describe articles within its scope and is
internally silent on defining the term.33 While plot twists are amusing at the
cinema, they are good for nothing but a law review article when spotted in
legislation.

25. 35 U.S.C. § 271(e)(1) (2015).

26. 35 U.S.C. § 156(c) (2015).

27. Id.

28. Proveris Sci. Corp. v. Innovasystems, Inc., 536 F.3d 1256, 1261 (Fed. Cir. 2008).

29. 35 U.S.C. § 156(c) (2015).

30. Id.

31. § 156(a).

32. § 156(f).

33. 35 U.S.C. § 271 (2015).



148 INDIANA HEALTH LAW REVIEW [Vol. 20:143

II. BACKGROUND: THE STATUS OF JUDICIAL INTERPRETATION

A. A Tale of Two Terms

Though the legislative Act prevented extending a patent monopoly during the
delay of FDA approval, it has not alleviated the judiciary’s interpretive role.
Litigation over the statutory scope of both applicable subject matter and activity
has been frequent. Two terms of § 271(e)(1) have received the most attention: the
scope of “patented invention,” as alluded to above; and the scope of “reasonably
related.”34 Debate concerning the former term seeks to characterize eligible
inventions by several criteria, which will be explored below, and debate
concerning the latter seeks to characterize what FDA approval activity the statute
intended to protect.

B. Reasonably Related

Naturally, a ‘reasonableness’ standard left ripe for judicial interpretation
results in substantial case law. This case law has shaped the outer boundaries of
the exemptions of § 271(e)(1), but the exact contours form only a blurry line.
Where § 156 offered tidy definitions to assist in assessing its reach, § 271(e)(1)
has instead relied on the generation of a sizable body of case law.35

1. Expansive Scope

What is “reasonably related” to FDA approval is perhaps the best understood,
and the least consequential, of the two terms. Reasonably related activity has been
held to include: early experimentation where some or even all information may
never be submitted to the FDA;36 experimentation with a patented peptide in
hopes of success and eventual FDA submissions for an Investigational New Drug
(“IND”) application;37 use of data from clinical study for purposes other than
FDA submissions; and activities targeting revision of a drug label.38 Further, the
protection of the safe harbor extends to drug production runs for qualification of
processes and equipment under a federal regulation.39 However, designating some
of the resulting product from a qualification run as “commercial inventory,”
though not decisive, risks forfeiture of the safe harbor.40 The Supreme Court case
of Merck, which considered early experimentation, is generally regarded as an
inflection point solidifying an expansive view of “reasonably related.”41 Merck

34. § 271(e)(1).

35. 35 U.S.C. § 156(f) (2015).

36. Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 206 (2005).

37. Integra Lifesciences I, Ltd. v. Merck KGaA, 496 F.3d 1334, 1341 (Fed. Cir. 2007).

38. Classen Immunotherapies, Inc. v. Elan Pharm., Inc., 786 F.3d 892, 899 (Fed. Cir. 2015).

39. Amgen, Inc. v. Hospira, Inc., 944 F.3d 1327, 1339-40 (Fed. Cir. 2019).

40. Id. at 1340 (two batches designated as “commercial inventory,” one was shielded, and

the other was not).

41. Daniel Wobbekind, Integra Lifesciences I, Ltd. v. Merck KGaA: Re-Examining the Broad



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 149

will be unfolded later in this Note with focus on how its broad language has an
inevitable influence on the scope of the patented invention.

2. Not Routine

One judicial limitation on what constitutes “reasonably related” under the
safe harbor looks at the type of submission which might be generated from the
activity.42 Specifically, courts distinguish between activity resulting in “routine”
and “not routine” submissions to the FDA.43 Though both types of activities may
be related to obtaining or maintaining FDA approval, only activities which are
deemed “not routine” are eligible for shielding under the safe harbor.44 While this
requirement receives particular attention with post-approval activity, its waiver
should not be assumed simply because a product has not yet received FDA
approval. Such an absolute rule might encourage gamesmanship on the part of the
manufacturer. For example, production of commercial product prior to FDA-
approval would be disallowed afterward while the controlling patent is still in
force. Accordingly, the court has allowed discretion on this matter and referred
to the American Heritage Dictionary to define “routine” as an activity which is
“habitual” or “regular.”45 Hence, the word “reasonable” does not merely convey
a degree of relatedness but also a second qualifying quality concerning the
activity’s output. So, factual relatedness, though necessary, is not alone sufficient
to satisfy “reasonably related.” The activity must also be non-routine.

As for sample submissions, which do not rise above routine, the Federal
Circuit has clarified among them are some activities, which are continued
throughout market availability –such as quality control processes and reporting
adverse effects of a vaccine when administered according to a patented low-risk
method.46 In contrast, protected ”non-routine” FDA reporting has been held to
include: (1) submissions to revise a drug label;47 (2) experimentation which has
the potential to result in an FDA submission;48 and (3) preparation for a
mandatory FDA pre-approval inspection.49

From a theoretical viewpoint, two characteristics are often used to signify
routine. First, as introduced above, the “regularity” of a submission–especially
one which would continue throughout market availability–supports the “routine-
ness” of the activity used to generate the submission.50 Second, an activity must

Scope of the S 271(e)(1) Safe Harbor, 23 BERKELEY TECH. L.J. 107, 138 (2008).

42. Id. at 1338.

43. Integra Lifesciences I, Ltd. v. Merck KGaA, 496 F.3d 1334, 1343 (Fed. Cir. 2007).

44. Momenta Pharm., Inc. v. Amphastar Pharm., Inc., 686 F.3d 1348, 1358 (Fed. Cir. 2012).

45. Momenta Pharm., Inc. v. Teva Pharm. U.S.A., Inc., 809 F.3d 610, 620 (Fed. Cir. 2015).

46. Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1072 (Fed. Cir. 2011);

see also Momenta Pharm, 809 F.3d at 618.

47. Elan Pharms, 786 F.3d at 898.

48. Integra Lifesciences I, Ltd. v. Merck KGaA, 496 F.3d 1334, 1340-48 (Fed. Cir. 2007).

49. Amgen, 944 F.3d at 1339-44.

50. Momenta Pharm, 809 F.3d at 620.



150 INDIANA HEALTH LAW REVIEW [Vol. 20:143

produce submissions presently required to obtain FDA approval – not merely
maintain FDA approval – for it to succeed at overcoming the bar against routine
submissions.51 The Federal Circuit’s use of legislative history affirms this as a
minimum.52 In short, if the alleged infringing activity produces a submission type
which continues during market availability, the activity is likely routine, and use
of the associated patented invention will likely not be shielded.

B. Patented Invention

Not surprisingly, the generic term “patented invention” of § 271(e)(1) of the
Hatch-Waxman Act invariably includes – at the very least53 – the use of a drug
when that use is “reasonably related” to obtaining FDA approval on that same
drug.54 In bounding that scope, the statutory language identifies no obvious
limitation to the statute’s patented invention. Indeed, § 271 uses “patented
invention” throughout to refer to all inventions without regard for their status
under federal regulations or otherwise.55 It is not clear whether the patented
invention shielded must be used in connection with its own FDA approval.
Further, it is not clear whether the patented invention must be subject to FDA
approval at all. By comparison, while the common law exception has the reach
of T-rex arms, the Act is linguistically poised with the reach of an orangutang
gliding through the treetops. Even so, courts have defined “patented invention”
with some particularity.56 While courts agree the term is not limited to
pharmaceutical drugs, a close look reveals courts disagree on whether the
patented invention’s regulatory status under the FDA is required.

1. Not All About Drugs

First, the Supreme Court in Eli Lilly v. Medtronic clarified that “patented
invention” includes “all inventions, not drug related inventions alone.”57

Unsurprisingly, it is settled that the statute shields the use of patented processes,
pharmaceutical manufacturing equipment, medical devices, and pharmaceuticals
from infringement when used to approve those technologies under their
respective FDA regulations.58 This holding aligns with the intent to ensure a
competitor can introduce a generic product to market immediately upon patent
expiration. Notably, the statement in Eli Lilly is made without caveat and has

51. Integra Lifesciences I, 496 F.3d at 1343.

52. Biogen IDEC, 659 F.3d at 1071 (quoting H.R. REP. NO. 98-857(I) at 45 (1984)).

53.  Proveris Sci., 536 F.3d at 1263.

54. 35 U.S.C. § 271(e)(1) (2015) (to the author’s knowledge, no case has excluded drugs

subject to FDA approval from the statutory reach of “patented invention”).

55. Id.

56. Id.

57. Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 665 (1990).

58. See Amgen Inc., 944 F.3d at 1338-40; Elan Pharm., Inc., 786 F.3d at 898; Proveris Sci.,

536 F.3d at 1262.



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 151

occasionally been read to suggest a contrast to the “product” of § 156, calling into
question whether the “patented invention” must itself be subject to FDA
approval.59

2. Invention’s Status Under Regulation

Following Eli Lilly, the next seeming expansion in the scope of what the
“patented invention” includes came from the Federal Circuit. In Abtox v. Exitron,
a defendant used a plasma sterilizer–not itself subject to § 156 or full FDA
approval60, and was granted summary judgement for non-infringement on its
motion to dismiss.61 The Abtox court reasoned the Supreme Court in Eli Lilly had
only indicated statutory symmetry between §156 and § 271 was “preferable but
not required.”62 Hence, according to the Abtox court’s interpretation, the
“products” of  § 156 need not refer to the same class of inventions as the
“patented invention” of § 271–presumably, § 271 including a broader class.63

Then, in 2005, the Supreme Court subtly weighed in on the subject in Merck
v. Integra Lifesciences.64 Though, Merck is often understood to turn on the
“reasonably related” term, as discussed above, there is an aspect of Merck’s
holding which is inextricable from the scope of a “patented invention.”65 As an
observational matter, a patented compound in the preclinical “twilight
zone”–having only hopes of proving therapeutic–is not yet, at the time of
experimentation, subject to FDA approval. Merck held such a patented
compound, not yet subject to FDA approval, was within the ambit of the safe
harbor.66 Public policy motivation for this outcome is centered on encouraging
experimentation with potentially useful, but patented compounds. Questions
remain whether this holding unacceptably erodes Eli Lilly’s preference for
statutory symmetry.

3. The Standing of the Research Tool

While Merck may have been written with the defining of “reasonably related”
in mind, it would appear the reader was struck with its profound effect on the
“patented invention” term. Specifically, Merck held that the safe harbor is not
necessarily forfeited when there is “use of patented compounds in experiments

59. Merck KGaA, 545 U.S. at 208 n.7.

60. Abtox, Inc. v. Exitron Corp., 122 F.3d 1019, 1029 (Fed. Cir. 1997) (held the sterilizer was

a Class II device not eligible for a patent term extension under § 156 because of its status as subject

to an abbreviated FDA approval process).

61. Id.

62. Id.

63. Abtox, 122 F.3d at 1027.

64. Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005).

65. Id.

66. See Merck KGaA, 545 U.S. at 206.



152 INDIANA HEALTH LAW REVIEW [Vol. 20:143

that are not ultimately submitted to the FDA.”67 Further, Merck interprets Eli Lilly
to hold § 271(e)(1) “exempted from infringement all uses of patented compounds
‘reasonably related’ to the process of developing information for submission
under any federal law regulating the manufacture, use, or distribution of drugs.”68

It is not hard to spot the implications while reading with the court’s own
emphasis. The patented compounds being used are not necessarily the same
compounds receiving, or subject to, the referenced FDA approval.

Merck’s broad view of § 271(e)(1) provoked a slew of articles warning the
demise of laboratory research tool development under the swelling safe harbor
of § 271(e)(1).69 Anchored in policy animating U.S. patent law, these critical
publications argued limited patent enforcement for research tool disclosures
would result in fewer patents being made public, less progress in the art by
advancements thereupon, and a reduction in related capital investment.70

Seventeen years later, questions remain whether Merck issued an “open season”
on the unlicensed use of patented research tools.

It is difficult to say to what extent these fears came to pass. Without a control
group (against which a meaningful change could be observed) or a dramatic
change in the generation of research tool technology, we can only tentatively say
the effects appear to have been minimal across the research tool industry. In
contrast, a noticeable effect certainly arose among the courts. A minority of cases
have in fact used this language from the Supreme Court in Merck to disassociate
the submission of FDA approval from the patented invention.71 Specifically, the
safe harbor has been used to protect the use of a patented invention for the
generation of data to be submitted pursuant to the FDA approval of a second
article.72 For example, in the 2013 case of Teva Pharms. v. Sandoz, the U.S.
District Court for the Southern District of New York extended the safe harbor to
patented polypeptide markers used to obtain molecular weight characteristics of

67. Id.

68. Id.

69. See Wolrad Prinz, Research Tool Patents After Integra v. Merck - Have They Reached

a Safe Harbor?, 14 MICH. TELECOMM. & TECH. L. REV. 367, 445 (2008); see also Tara Stuart, Has

The Supreme Court Incorrectly Expanded S 271(e)(1) to Risk a Regulatory Taking?, 5 J.

MARSHALL REV. INTELL. PROP. L. 216, 237 (2006); Joshua D. Sarnoff & Christopher M. Holman,

Recent Developments Affecting the Enforcement, Procurement, and Licensing of Research Tool

Patents, 23 BERKELEY TECH. L.J. 1299, 1365 (2008).

70. See generally Daniel Wobbekind, Integra Lifesciences I, Ltd. v. Merck KGaA: Re-

Examining the Broad Scope of the S 271(e)(1) Safe Harbor, 23 BERKELEY TECH. L.J. 107, 138

(2008) (arguing funds for research will be stifled without patent enforceability); Brendan M.

O'Malley, Merck v. Integra and Its Aftermath: A Safe Harbor for the Commercial Use of

Biotechnology Research Tools?, 23 CARDOZO ARTS & ENT. L. J. 739, 760 (2006) (arguing an

immediate financial impact to researchers and long-term impact on public welfare).

71. See Teva Pharms. USA, Inc. v. Sandoz Inc., No. 09 CIV. 10112, 2013 WL 3732867

(S.D.N.Y. July 16, 2013).

72. Id.



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 153

an active ingredient in a drug.73 The shielded markers are not a drug nor subject
to FDA approval.74 Specifically, these markers are only used to extract data from
the marketable drug, data which is then submitted to the FDA for approval of the
marketable drug.75 Hence, the polypeptide markers fall squarely within the
research tool class of inventions. Though the Merck Court explicitly declined to
address the issue of research tools,76 the Merck holding was used in deciding the
Sandoz case which involved research tools.77 The Supreme Court’s refusal to
acknowledge research tools as a distinct class has perhaps inadvertently brought
them under the broad principles above and did not foreclose the use of Merck in
that context.

4. Narrowing at the Federal Circuit

Perhaps in response to a recognized need, or echoing concern for research
tool patents, eighteen years after Eli Lilly, and three years after Merck, the Federal
Circuit seemingly carved out a limitation on the statutory “patented invention.”
In Proveris v. Innovasystems, the Federal Circuit held that the use of Innova’s
laboratory equipment–not itself subject to FDA approval, but used exclusively in
producing data for FDA approval–was not shielded by the safe harbor of §
271(e)(1).78 The Federal Circuit reasoned that since excluding Innovasystems
from use of the patented device would not unfairly extend the life of the patent
by an approval delay, the purpose of the safe harbor would not be served in
applying it in that instance.79 The Federal Circuit explains this in plain terms:

Innova is not a party seeking FDA approval for a product in order to
enter the market to compete with patentees. Because the OSA device is
not subject to FDA premarket approval, and therefore faces no regulatory
barriers to market entry upon patent expiration, Innova is not a party
who, prior to enactment of the Hatch-Waxman Act, could be said to have
been adversely affected by the second distortion. For this reason, we do
not think Congress could have intended that the safe harbor of §
271(e)(1) apply to it.80

In this excerpt, the Proveris court underscores key rationale and issues a
single result in harmony with this Note’s call for a bright-line rule. This decision
strengthened the case for a general rule excluding patented inventions not subject
to FDA approval from the safe harbor. However, Sandoz–decided about five

73. Sandoz, 2013 WL 3732867, at *1.

74. Id. at *2.

75. Id.

76. Merck KGaA, 545 U.S. at 205 n.7.

77. Sandoz, 2013 WL 3732867, at *8.

78. Proveris Sci. Corp., 536 F.3d at 1266.

79. Id. at 1265.

80. Id.



154 INDIANA HEALTH LAW REVIEW [Vol. 20:143

years after Proveris–has not been recognized as establishing a binding rule.81 It
would appear this is because of the Supreme Court’s unwillingness to concur on
such a categorical limitation.

In the face of such binding Federal Circuit guidance, how did Sandoz justify
a dismissal of patent infringement for use of the patented polypeptide marker?
Surprisingly, Sandoz does not interpret Proveris to narrow, or even consciously
impact, the statutory “patented invention.”82 Instead, Sandoz emphasizes
Proveris’s reliance on the statute’s requirement that activity is “solely for uses”
related to FDA approval.83 Sandoz points out that in Proveris, the defendant was
“manufacturing and selling a patented device” and argued their “customers’
activities”–being in connection with seeking FDA approval–were a basis to grant
the defendant shelter under the safe harbor.84 The defendant wanted to sell a
patented product to a customer who would use it in connection with FDA
approval.85 Accordingly, had the defendant in Proveris been the one using the
patented invention, according to Sandoz at least, the safe harbor may very well
have applied.86 To clarify, Sandoz expressly concludes that to read Proveris to
hold that laboratory equipment forms a class of devices generally unprotected by
the safe harbor would be to “read Proveris too narrowly.”87 In Sandoz’s view,
Proveris did not exclude laboratory equipment, a subset of research tools, from
the reach of the safe harbor, but rather, the use of a patented invention where the
user was not seeking FDA approval.88 To construct Proveris so narrowly is, in
this author’s opinion, to corrupt the context and conflate the audience with the
actors. Regrettably, whether FDA approval was sought concerning the patented
invention was left optional.

D. Summary of Uncertainty Concerning Research Tools

Today, all these factors have produced uncertainty concerning the safe
harbor’s effect on the species of patented invention, commonly referred to as
research tools.89 Generally, research tools are not subject to FDA approval,
though they are often required to generate data demanded by FDA submissions.
Sandoz is a district court decision in which a research tool was brought under the
safe harbor, but Sandoz is in the minority on this holding.90 Proveris, on the other

81. Sandoz, 2013 WL 3732867, at *8.

82. Id. at *7.

83. Id. at *8. 

84. Id.

85. Id.

86. Id.

87. Id.

88. Id.

89. Merck KGaA, 545 U.S. at 208 n.7.

90. To this author’s knowledge, Sandoz is the only district court which has explicitly included

in the scope of “patented invention” drugs not themselves subject to FDA approval – many district

courts have remained silent on the issue.



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 155

hand, is a Federal Circuit decision in which a research tool was excluded from the
safe harbor.91 Though the Supreme Court has used broad terms to define the safe
harbor’s “patented invention” and expressly avoided answering the question of
whether a research tool is shielded under § 271(e)(1), at least two district courts
have read Proveris to categorically exclude research tools as a “patented
invention” under § 271(e)(1).92

In contrast, the Sandoz decision from the Southern District of New York
above dismissed multiple patent infringement claims arising from the use of
patented polypeptide markers to measure the molecular characteristics of a
generic drug seeking FDA approval.93 Characteristic of most research tools, the
polypeptides were themselves not subject to FDA approval.94 Interpreting Abtox,
the district court in Sandoz firmly asserted that “[i]n construing that all classes of
medical devices fell within the scope of the safe harbor (not just those subject to
FDA approval), the Federal Circuit relied upon the language of the statute and the
Supreme Court's broad language in Eli Lilly.”95 With the Supreme Court holding
a broad view of which inventions fall under the safe harbor, the Federal Circuit
now construing that precedent narrowly, and district courts landing on both sides
and in-between, some enterprising innovators have been willing to risk litigation
rather than seek licensing on crucially important technologies.

III. USE NOW, LITIGATE LATER

A. Two Controversies

Two patent infringement lawsuits, one still pending, highlight the uncertainty
around research tools under the safe harbor. Allele Biotechnology &
Pharmaceuticals Inc. filed suit against two defendants in two different Federal
District Courts on the same day.96 Allele filed against Regeneron in the United
States District Court for the Southern District of New York on October 5, 2020,97

and against Pfizer in the United States District Court for the Southern District of
California.98 The lawsuits both allege infringement of the same patented

91. Proveris Sci. Corp., 536 F.3d at *1261.

92. Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-01958-H, 2021 U.S. Dist.

LEXIS 85347, at *12 (S.D. Cal. May 4, 2021).

93. Teva Pharma. USA, Inc. v. Sandoz Inc., 2013 WL 3732867, *2 (S.D.N.Y. 2013).

94. Id.

95. Id. at *7.

96. Regeneron has its principal place of business, maintains its registered office, and is

incorporated in the State of New York. Complaint, Allele Biotechnology & Pharm., Inc. v.

Regeneron Pharm., Inc., No. 20-cv-08255, 2021 WL 2880694, at *1 (S.D.N.Y. Apr. 8, 2021). Thus,

venue was proper and easy to attain in the Southern District of New York.

97. Complaint, Allele Biotechnology & Pharm., Inc. v. Regeneron Pharm., Inc., No. 20-cv-

08255, 2021 WL 2880694, at *1 (S.D.N.Y. Apr. 8, 2021).

98. Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-01958-H, 2021 U.S. Dist.

LEXIS 85347, at *1 (S.D. Cal. May 4, 2021).



156 INDIANA HEALTH LAW REVIEW [Vol. 20:143

technology expressly identified as a research tool. Further, the alleged activity of
the defendants did not materially differ. Both defendants, among other alleged
activity, used mNeonGreen in neutralization assays which inserted a gene
chimera from Allele’s fluorescent protein into the SARS-CoV2-19 viral genome
for purposes of tracking its proliferation and related behavior.99 The choice to file
in two different jurisdictions, though perhaps essential to easily ensure proper
venue, may prove to highlight a particular uncertainty in the law on an integral
issue.

Four subjects will be considered briefly. First, the prospect of the remaining
case going to trial, and its suitability for appeal and clarification of an unresolved
issue of the safe harbor’s interpretation will be addressed in this section. Second,
this section will consider whether the relevant analysis offered by the court so far
is legally satisfying. Third, this section will provide a brief consideration of the
possible outcomes. Lastly, a bright-line rule will be proposed which aims to
resolve statutory ambiguity.

1. Patent at Issue

Prior to the spread and discovery of SARS-CoV2-19, Allele had developed
and patented mNeonGreen – a monomeric fluorescent protein – as United States
Patent No. 10,221,221.100 Such a protein is useful as a biomarker to track or
identify certain molecules and, among other applications, gives researchers a
window into the effectiveness of therapeutics designed to generate antibodies.101

In an effort to enhance the standing of its cases against Regeneron and Pfizer,
Allele argued mNeonGreen is the best fluorescent protein available and has been
referred to objectively by third-parties as the “[k]ing of fluorescent proteins.”102

2. Accused Activity

Before Pfizer, or any other therapeutic developer was directly involved, a
university used mNeonGreen to develop the “gold standard” COVID-19 assay for
evaluating vaccine effectiveness and differentiating between which therapeutic
was most and least effective.103 Allele alleges Pfizer and BioNTech then used this
assay, along with the patented florescent protein, for commercial testing,
development, and ultimately selection of their mRNA prophylactic COVID-19
vaccine during clinical trials.104 By testing antibody levels of patients during
clinical trials, Pfizer selected a winning vaccine from among several BNT162

99. AmendedComplaint at 4, Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-

01958-H, 2021 U.S. Dist. LEXIS 85347 (S.D. Cal. Feb. 25, 2021).

100. Id. at 2.

101. Id. at 4.

102. Id. at 6.

103. Id. at 2.

104. Id.



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 157

mRNA candidates.105 Similarly, Allele alleges Regeneron Pharmaceuticals used
mNeonGreen to detect a pseudoparticle reporter indicating the presence of SARS-
CoV-2 neutralizing antibodies.106 In sum, Allele alleged both Pfizer and
Regeneron emerged as front runners in the race to a vaccine precisely because of
their unlicensed use of mNeonGreen.107 Noting mNeonGreen is not itself subject
to premarket approval under any federal law, Allele argued against applying the
safe harbor.108

3. Legal Issue: Complaint and Defense

Allele, in both complaints alleging infringement of the 221 patent,
specifically identify mNeonGreen as a research tool.109 In addition to denying
nearly all of Allele’s allegations, asserting Allele’s patent is invalid, and asserting
non-infringement of the patent, Pfizer raised § 271(e)(1) as an affirmative defense
against patent infringement.110 Accordingly, Pfizer filed a motion to dismiss the
lawsuit, arguing its use of mNeonGreen was sheltered by the statutory safe
harbor.111

Similarly, Regeneron filed a motion to dismiss under Federal Rules of Civil
Procedure 12(b)(6), arguing Allele had failed to state a claim upon which relief
could be granted.112 As expected, Regeneron filed its support to this motion on
August 20, 2021.113 Unsurprisingly, it ardently pointed out that Sandoz expressly
included research tools in the safe harbor: emphasizing Sandoz’s found that
“‘[t]he statutory safe harbor is clear’ and ‘patented invention’ is defined by 35
U.S.C. § 100(a) to broadly mean ‘invention or discovery.’”114 Further, Regeneron
argues that whatever Proveris stated concerning the term “patented invention,”

105. Id. at 10-11.

106. Amended Complaint at 9, Allele Biotechnology & Pharm., Inc. v. Regeneron Pharm.,

Inc., No. 20-cv-08255, 2021 WL 2880694 (S.D.N.Y Apr. 8, 2021).

107. AmendedComplaint at 11, Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-

01958-H, 2021 U.S. Dist. LEXIS 85347 (S.D. Cal. Feb. 25, 2021); see also Second

AmendedComplaint at 10, Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-01958-H,

2021 U.S. Dist. LEXIS 85347 (S.D. Cal. Feb. 25, 2021).

108. Id. at 7.

109. Id. at 11; see also AmendedComplaint at 12, Allele Biotechnology & Pharm., Inc. v.

Pfizer, Inc., No. 20-cv-01958-H, 2021 U.S. Dist. LEXIS 85347 (S.D. Cal. Feb. 25, 2021).

110. Answer at 34, Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-01958-H,

2021 U.S. Dist. LEXIS 85347 (S.D. Cal. June 3, 2021).

111. Motion to Dismiss at 1, Allele Biotechnology and Pharmaceuticals, Inc. v. Pfizer Inc.,

20-cv-01958-H-AGS, 2021 WL 2774550 (S.D. Cal. April 23, 2021).

112. Notice of Motion at 1, Allele Biotechnology & Pharm., Inc. v. Regeneron

Pharmaceuticals, Inc., No. 20-cv-08255, 2021 WL 2880694 (S.D.N.Y Aug. 20, 2021).

113. Reply Memorandum of Law at 2, Allele Biotechnology & Pharm., Inc. v. Regeneron

Pharmaceuticals, Inc., No. 20-cv-08255, 2021 WL 2880694 (S.D.N.Y Aug. 20, 2021).

114. Id. at 2 (quoting Teva Pharm’s USA, Inc. v. Sandoz, Inc., 2013 WL 3732867, at *7

(S.D.N.Y. 2013)).



158 INDIANA HEALTH LAW REVIEW [Vol. 20:143

and a dependence on it being subject to FDA approval, was mere dicta because
Proveris itself did not turn on that holding.115 Rather, Regeneron argues, Proveris
rejected application of the safe harbor “because the defendant’s use was not
related to generating data for FDA submission.”116 Asserting Proveris offered
only dicta on the scope of “patented invention” appears to be bold, and in the
minority view. However, the case has been filed in a jurisdiction which has
shown favor to that vary approach and the litigation remains pending.

B. Status of Pfizer Litigation

1. Motion to Dismiss Denied

The action against Pfizer was filed with the United States District Court for
the Southern District of California. Prior to resolution by settlement on January
5th, 2022, three orders on motions were issued from Judge Marilyn L. Huff.117

Two related to motions to dismiss and compel, respectively, and are of little
import to the safe harbor issue.118 Of particular interest, in May 2021, the Court
denied Pfizer's motion to dismiss under Federal Rules of Civil Procedure 12(b)(6)
on the theory that, as a matter of law, Allele had failed to state a claim upon
which relief could be granted.119

According to Pfizer, even if the patent was valid and Pfizer’s activity
constituted elements of infringement, as Allele alleges, the activity was shielded
under the safe harbor of § 271(e)(1) and, as such, Allele was never entitled to any
of the relief it requested.120 In denying this motion, the Court noted that two
Federal District Courts have held research tools, which are not subject to FDA
approval, are not shielded under the safe harbor.121 Though the legal standard for
a successful 12(b)(6) favors the plaintiff,122 the U.S. District Court for the

115. Id.

116. Id. at 1-2.

117. See Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-01958-H, 2021 U.S.

Dist. LEXIS 37287 (S.D. Cal. Feb. 26, 2021). See also Allele Biotechnology & Pharm., Inc. v.

Pfizer, Inc., No. 20-cv-01958-H, 2021 U.S. Dist. LEXIS 174654 (S.D. Cal. Sep. 13, 2021).

118. Id.

119. Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., 20-cv-01958-H-AGS, 2021 U.S. Dist.

LEXIS 85347, at *3 (S.D. Cal. May 4, 2021).

120. Id. at *5.

121. Id. at *11. See also Isis Pharms., Inc. v. Santaris Pharma A/S Corp., No. 11CV02214,

2012 U.S. Dist. LEXIS 134107, 2012 WL 4111157, at *4 (S.D. Cal. Sept. 19, 2012) ("The Safe

Harbor does not apply, however, when a biological compound is used to perform 'basic scientific

research' or as a 'research tool.'"), and PSN Ill., LLC v. Abbott Labs. & Abbott Bioresearch Ctr.,

Inc., No. 09 C 5879, 2011 U.S. Dist. LEXIS 108055, 2011 WL 4442825, at *5 (N.D. Ill. Sept. 20,

2011) ("Proveris excluded research tools from the purview of the safe harbor exemption.").

122. Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., 20-cv-01958-H-AGS, 2021 U.S. Dist.

LEXIS 85347, at *4 (requiring all questions of fact to be resolved in favor of the non-moving

party).



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 159

Southern District of California suggested, in its refusal to dismiss the action
against Pfizer, that it reads Eli Lilly and Proveris to teach research tools are
outside the scope of the “patented invention” of § 271(e)(1).123

Interestingly, discussion of the Supreme Court case of Merck–a case which
contains what some have viewed as expansive language suggesting research tools
rest within the ambit of § 271(e)(1)–is limited to one paragraph and avoided
entirely in the court’s analysis section.124 Aside from several quotes unanchored
by meaningful context, the Court reports Merck’s broadest statement only in
parentheses and removes the Supreme Court’s emphasis. Indeed, the Court’s lack
of focus on Merck suggested it would not extend Merck’s sweeping principles to
research tools.125 Notably, Merck was seemingly replaced with a discussion easily
distinguishing Classen v. Elan Pharms in the Court’s brief analysis and
subsequent rejection of Pfizer’s motion to dismiss.126 Perhaps Merck’s direct
refusal to address research tools has been taken by some courts to relieve its
application of the general statements therein.127 The appropriateness of this
maneuver will be considered later.

Though not excepted by all courts, the U.S. District Court for the Southern
District of California made it clear, as a matter of law, the safe harbor would not
shield Pfizer’s activity.128 Since juries generally favor patent holders, the parties
could assess their chances of success and the outcome of the jury trial which was
set for late 2022. This proved enough information to settle. It is safe to say the
terms of the settlement were in Allele’s favor–favor obviously dependent on the
Court’s refusal to apply the safe harbor.

2.  Status of Regeneron Litigation

A similar motion to dismiss was filed by Regeneron on August 8, 2021, with
the Southern District of New York, which was dismissed on March 2, 2022.129 A
status update from Allele on December 13, 2021, indicated Regeneron had ceased
all use of mNeonGreen in its current research and development of next generation
antibody cocktails and notified Allele.130 Allele has accordingly withdrawn

123. See Santaris Pharma A/S Corp., U.S. Dist. LEXIS 134107, at *4 ("The Safe Harbor does

not apply, however, when a biological compound is used to perform 'basic scientific research' or

as a 'research tool.'"), and Abbott Labs. & Abbott Bioresearch Ctr., Inc., U.S. Dist. LEXIS 108055,

at *5 ("Proveris excluded research tools from the purview of the safe harbor exemption.").

124. Id.

125. Id. at *8.

126. Elan Pharm., Inc., 786 F.3d at 896-97 (the court states the defendant’s reliance on Elan

Pharm. is misplaced because the issue relates strongly to the nature of the activity instead of the

invention being used).

127. Allele Biotechnology & Pharm., Inc., 2021 U.S. Dist. LEXIS 85347, at *15.

128. Elan Pharm., Inc., 786 F.3d at 896-99.

129. Status Update at 1, Allele Biotechnology & Pharm., Inc. v. Regeneron Pharmaceuticals,

Inc., No. 20-cv-08255, 2021 WL 2880694 (S.D.N.Y Apr. 8, 2021).

130. Id.



160 INDIANA HEALTH LAW REVIEW [Vol. 20:143

associated allegations of continued use of their patented technology, but has
retained other allegations.131 While Regeneron’s move is difficult to legally
construe, it could be an indication both parties are also likely to negotiate a
settlement.

3. Settlement of Trial: Jury or Bench

With about 96 percent of patent infringement lawsuits settled before trial,132

it is statistically unlikely that an individual case would receive a written opinion
from a judge on appeal, though a case is slightly more likely to be resolved on a
granting of summary judgment.133 With some lawsuits being dismissed or
abandoned, only about 1.5 percent of filed patent infringement lawsuits are
litigated to a conclusion.134 Of these, however, an increasing number are being
submitted to a jury for deliberations.135 Though jury trials significantly increase
both the chances a patent holder wins and their corresponding average award,136

they are the costliest form of resolution.137 For a jury trial to advance, both parties
must sharply disagree on what damages, if any, will restore the interests of the
plaintiff. For cases of ordinary circumstances–where damages from comparable
lawsuits are readily available–settlement is likely in the best interest of both
plaintiff and defendant. Time and resources consumed by trial are often not worth
the statistically larger award.

Allele, however, filed a case against Pfizer which was not average in several
respects. It was arguably worth an extraordinary reward. When viewed as a single
industry, biotech and pharmaceuticals garner infringement damages which dwarf
those of other industries.138 Further, Pfizer has made a veritable fortune from the
vaccine.139 If Allele had been left to convince a jury Pfizer was first to an
effective therapeutic because of a deliberate and unauthorized use of
mNeonGreen, Allele would have also happily asked that jury to consider exactly

131. Id.

132. Branka Vuleta, 25 Patent Litigation Statistics-High-Profile Feuds About Intellectual

Property, LEGALJOBS (Aug. 6, 2021), https://legaljobs.io/blog/patent-litigation-statistics/#:~:text=

A%3A,year%20in%20the%20United%20States [https://perma.cc/W59F-XZ7H].

133. Id.

134. Id.

135. Id.

136. Landan Ansell et al., 2018 Patent Litigation Study, PRICE WATERHOUSE COOPERS 1, 6-7

(May 2018), https://www.ipwatchdog.com/wp-content/uploads/2018/09/2018-pwc-patent-litigation-

study.pdf [https://perma.cc/8HN5-33CQ].

137. Vuleta, supra note 132.

138. Ansell et al., supra note 136 (in a 20-year study where the median damage award over

all industries was $5.9 million, the Biotech/Pharma industry had a median award per case

exceeding $20 million).

139. Zachary Brennan, Moderna's Covid-19 Vaccine Sales to Trail Pfizer's Total Significantly

in 2021 and 2022, ENDPOINTS NEWS (Aug. 5, 2021), https://endpts.com/modernas-covid-19-

vaccine-sales-to-trail-pfizers-total-significantly-in-2021-and-2022/ [https://perma.cc/A8J4-33EB].



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 161

what part of Pfizer’s projected $33 billion in 2021 revenue belongs to Allele.140

Though Pfizer has settled, an analogous consideration applies against Regeneron
with respect to the wide use of its antibody cocktail–including the high-profile
treatment of then-President Donald Trump, after he contracted the illness prior
to vaccine availability. 

Pleadings in both cases force an answer on the research tool question–an
unresolved conflict which has garnered much attention. Though Allele has
resolved Pfizer’s case without option to refile, it is conceivable that amicus briefs
and similarly interested parties would aptly vie for resolution on this issue. This
factor suggests Regeneron’s case may be ripe for escalation to higher courts.
High-profile players produced a product which has become a household name on
a global scale–largely due to the significance of the COVID-19 outbreak.141 The
accompanying money, motive, and resources may help extrude a final answer to
the research tool question.   

IV. ANALYSIS

A. On The Denial of Motions for Summary Judgement

1. Right Outcome

It is helpful to understand the significance of the denial to grant Pfizer’s
motion to dismiss. Pfizer asserted a motion to dismiss because of Allele’s alleged
“failure to state a claim upon which relief can be granted.”142 For this motion to
succeed against the plaintiff, the pleadings must not contain “enough facts to state
a claim to relief that is plausible on its face.”143 In determining this, the court may
ignore naked assertions and legal conclusions, amounting to formulaic recitations
of the elements of the cause of action–but only when they are lacking further
factual enhancement.144 The burden of establishing a facially plausible claim rests
with the plaintiff and factual disagreement is to be resolved in favor of the non-
moving party.145 After a conforming Rule 8 pleading is submitted by the plaintiff,
the burden then shifts to the defendant to show, even if the alleged facts are true,
the plaintiff would not be positioned to collect any remedy.146 Here, Pfizer’s
argument rested principally on the safe harbor for protection to bar Allele from
any recovery. With the scope of the safe harbor being one of contention and the

140. Id.

141. Id.

142. FED. R. CIV. P. 12(b)(6).

143. Bell Atl. Corp. v. Twombly, 550 U.S. 544, 570 (2007).

144. Id. at 557, 564.

145. Daniel C. Cooley & Justin E. Loffredo, A Refresher on the Standards of Pleading Direct

Patent Infringement, IP LITIGATOR (Dec. 2020), https://www.finnegan.com/en/insights/articles/a-

refresher-on-the-standards-of-pleading-direct-patent-infringement.html [https://perma.cc/497Y-

HDWR].

146. Id.



162 INDIANA HEALTH LAW REVIEW [Vol. 20:143

precedent of the Southern District of California, denial of a motion to dismiss was
not surprising. Even so, the scope of the safe harbor will likely be questioned
again in the Southern District of California. Similarly, and relying on similar
rationale, the March 2nd denial of Regeneron’s motion to dismiss will likely not
be the last time the scope of the safe harbor is at issue in the Southern District of
New York.147 Indeed, it may be raised again in later proceedings involving this
same litigation.

Whether the § 271(e)(1) safe harbor applies is a mixed question of law and
fact. As to law, it depends on the definition of the “patented invention” of §
271(e)(1). As to fact, it depends on what mNeonGreen is and where it falls in
relation to the judicially endorsed definition. Whether these questions coincide
in the law-fact continuum remains a mystery, and so, it is no surprise the court
ultimately dismissed both defendant’s motions for summary judgement. Based
on variation between courts, it is difficult to say whether mNeonGreen, though
it be a research tool, falls under the purview of the safe harbor. It is important to
note that the court only stated Pfizer had “failed to demonstrate that the facts
alleged in the [complaint] establish that the allegedly infringing activity is
exempted” under the safe harbor.148 The court may be alluding to an answer
turning on activity instead of subject matter contemplated by the “patented
invention” of the safe harbor.

2. Limited Rationale

The court, in its denial to dismiss the case against Pfizer, points out that the
defendant’s reliance on Sandoz is unpersuasive and ineffectual because it is a
non-binding district court opinion.149 However, this same rationale disembowels
its own reliance on two district courts who have interpreted Proveris to
categorically exclude items not subject to FDA approval from the “patented
invention” of § 271(e)(1).150 The court resorts to ‘cherry picking’ of lateral, non-
binding interpretations of Proveris exactly because its binding precedent–the
Federal Circuit and Supreme Court–have not yet enunciated the bright-line rule
it seeks. Federal District Courts have been criticizing each other’s interpretation
of their mutually binding precedent. This silence to-date by the Federal Circuit
and Supreme Court raises questions of unacceptable ambiguity for those who
innovate in the field of research tools.

The court, in Allele’s case against Pfizer, quotes from Proveris to purportedly
show a rule requiring an invention be subject to FDA approval to receive safe

147. See Cooley & Loffredo, supra note 145.

148. Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-01958-H, 2021 U.S. Dist.

LEXIS 85347, at *18 (S.D. Cal. May 4, 2021).

149. Id. at *17.

150. Id. at *12; see also Eli Lilly & Co. v. Medtronic, Inc., 496 U.S. 661, 665, 672 (1990) (to

state “all inventions, not drug related inventions” are within the ambit of § 271(e)(1) formally

marks at least one aspect of asymmetry between § 156 and § 271).



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 163

harbor protection.151 After noting Proveris’ patented device is not eligible for §
156 patent term extension because it is not subject to FDA approval, the Proveris
court added that “because Innova's OSA device also is not subject to a required
FDCA approval process, it does not need the safe harbor protection afforded by
35 U.S.C. § 271(e)(1).”152 The Court relies heavily on this quotation. While it is
true Proveris goes on to treat subjection to FDA approval as a requirement to be
under the safe harbor, the last word on that subject from the Supreme Court was
only that such symmetry be “preferable.”153 Was Proveris wrong to add a
limitation the Supreme Court did not? Was this language mere dicta, as Sandoz
surmised? Such a reading of Proveris may conflict with the holding in Merck,
where the patented peptides only had hopes of producing material for FDA
submissions but were nonetheless protected.154 Is the rule potential subjection to
FDA regulation? Further, Abtox, the Federal Circuit decision, where a non-FDA
regulated plasma sterilizer was shielded by the safe harbor, has not been
overruled.155 In sum, whether a district court should require a product be subject
to FDA approval for application of the safe harbor is a matter reasonable
interpretations of current case law can (and do) differ on.

Further, three times throughout the denial of the motion to dismiss, the
California district court emphasizes the ‘perfect “product” fit’ described in Eli
Lilly.156 While the symmetry between § 156 and § 271 is dependent on an
invention itself being subject to FDA approval, Eli Lilly used this fact to explain
why § 271(e)(1) extended to a patented medical device, refusing to limit its scope
to drugs, to maintain this symmetry. This maneuver by some was regarded as
expanding a term once presumptively limited to drugs. Though the connection is
perfectly logical, Eli Lilly is not the latest binding precedent a district court must
reconcile before arriving at a conclusion. Merck was decided in 2005 and builds
on Eli Lilly to extend–not limit–the scope of § 271(e)(1) inventions. Referring to
Eli Lilly, Merck states it is “apparent from the statutory text that § 271(e)(1)'s
exemption from infringement extends to all uses of patented inventions that are
reasonably related to the development and submission of any information under
the FDCA.”157 Whether “any information” signifies that the information need not
relate to approval of the subject patented invention has not been answered by the
Supreme Court, and as we have already seen, is a subject of disagreement in
lower courts.158

It has been over fifteen years since this textualistic statement of the statute
concerned holders of research tool patents. Admittedly, the context is principally

151. Id. at *9.

152. Proveris Sci. Corp. v. Innovasystems, Inc., 536 F.3d 1256, 1266 (Fed. Cir. 2008).

153. Eli Lilly & Co., 496 U.S. at 666.

154. Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 208 (2005).

155. Abtox, 122 F.3d at 1029.

156. Allele Biotechnology & Pharm., Inc., 2021 U.S. Dist. LEXIS 85347, at *11, *13, *17.

157. Merck KGaA, 545 U.S. at 202.

158. See Teva Pharms. USA, Inc. v. Sandoz, Inc., No. 09 CIV. 10112, 2013 WL 3732867, at

*6-7 (S.D.N.Y. July 16, 2013).



164 INDIANA HEALTH LAW REVIEW [Vol. 20:143

aimed at defining the “reasonably related” phrase in the statute.159 However, in
the same way Merck (primarily concerned with the scope of reasonably related)
harmonizes with Eli Lilly (primarily concerned with the scope of patented
invention), a more fulsome explanation must bound the broad principles in Merck
as limited to the context of reasonably related activity and not conflicting with a
yet to be articulated general rule concerning research tools. Again, the scope of
“reasonably related” has not been defined in isolation: courts can and have woven
themes of reasonably related into analysis evaluating research tools as patented
inventions.160 With the significance of the patented invention’s subjection to FDA
approval formally left open for the lower courts, Allele presents a high-profile
opportunity where an unlicensed use of a patented research tool may be analyzed
to provide clarity on that point.161

3. Final Outcome

Inconsistency between courts on this matter is not a distant obscurity. A
student of the subject need only assess the probable outcome of these two cases
based on each jurisdiction’s precedent. As illuded to above, prior to settlement,
Allele’s complaint in the Southern District of California survived a motion to
dismiss and the jurisdiction has recent precedent categorically excluding patented
inventions not subject to FDA approval from the safe harbor. Collectively, this
suggests the Southern District of California is unlikely to extend the safe harbor
to immunize the future use of patented research tools. Indeed, this is not the first
time, or the last time, the Southern District of California has articulated a narrow
reading of Proveris.162 

In contrast, the Southern District of New York, in which Allele has filed suit
against Regeneron, has a recent case where the use of so-called research tools was
shielded under the safe harbor. Therefore, it once appeared two cases alleging
similar use of the same patented invention were queued up for different outcomes.
However, on March 2, 2022, Regeneron’s motion to dismiss, a motion analogous

159. Justice Scalia is known for strict textualistic reading of statutes and was often skeptical

of using legislative history to interpret statutes. He argued it could often support both sides and may

have been produced to yield an interpretation not voted on by Congress. See Merck KGaA, 545

U.S. at 202, 206, 208 (in each passage Scalia refuses to impose a limitation on “patented invention”

which was not introduced by the statute’s text).

160. See Teva Pharms. USA, Inc., 2013 WL 3732867, at *6 (quoting from Merck specifically

when assessing whether the patented invention used must itself be subject to FDA approval). See

also Allele Biotechnology & Pharm., Inc., 2021 U.S. Dist. LEXIS 85347, at *7 (reconciling Merck

with its narrower application of the safe harbor in the context of “patented invention”).

161. Merck KGaA, 545 U.S. at 208 n.7 (footnote 7 in Merck states that though the Court of

Appeals argued limiting § 271(e)(1) was appropriate to protect patents on research tools, the

Supreme Court explicitly declined to “express a view about whether, or to what extent,” research

tools should fall under the safe harbor).

162. See Isis Pharms., Inc. v. Santaris Pharma A/S Corp., No. 11-cv-02214, 2012 U.S. Dist.

LEXIS 134107, at *11 (S.D. Cal. Sept. 18, 2012).



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 165

to Pfizer’s motion, was similarly denied. As of July 31, 2022, both parties are
preparing for a jury trial, the outcome of which will likely raise the research tool
question again on appeal. Whether on appeal in this case, or in future cases with
arguably distinguishable facts, the contradictory case law will be advanced, and
the judge will resolve each case. This scenario is contrary to the desire for
consistency in the law and raises questions related to forum shopping, equity, and
predictability of the patent laws.

B. The Future of the Controversy

1. An Important Opportunity

Several factors unique to Allele’s case against Regeneron make it a candidate
to solidify the status of research tools under § 271(e)(1). First, there is no dispute
as to the nature of mNeonGreen—it is squarely a research tool and used as such
in the allegedly infringing activity. Relatedly, it is not itself subject to FDA
approval. Second, though the Proveris holding will almost certainly be
considered relevant, the aerosol spray analyzer in that case was not in fact used
for research by the defendant.163 Rather, it was used for measuring data from a
fully designed consumer product—the data required by the FDA before sale.164

Further, the aerosol spray analyzer in Proveris was being sold by the defendant
to third parties who would use it for obtaining data for FDA submissions. In other
words, Innova was making the device to sell it for a direct profit, not conduct
research themselves—potentially more scandalous than in-house use of a
molecular compound. Notably, mNeonGreen is used for research of promising
compounds, in identifying one which may be advanced and eventually require
submission to the FDA. In that sense, there are factual similarities with Merck.165

Though it is not the actual compound with hopes of FDA submissions being
directed at it, as in Merck, mNeonGreen appears to have been genetically integral
to those very compounds for the purposes of research.166 In short, Proveris may
be distinguishable, as mNeonGreen is the quintessential research tool.

Thirdly, the financial stakes could scarcely be higher. Though the parties are
not financial equals, both have adequate access to funding to fully litigate the
matter.167 Alleles technology was powerful. To illustrate, mNeonGreen assisted

163. Proveris Sci. Corp., 536 F.3d at *1264.

164. Id.

165. Merck KGaA, 545 U.S. at 193 (Merck states Ҥ 271(e)(1) exempts from infringement the

use of patented compounds in preclinical research, even when the patented compounds do not

themselves become the subject of an FDA submission.”).

166. Amended Complaint at 4, Allele Biotechnology & Pharm., Inc. v. Pfizer, Inc., No. 20-cv-

01958-H, 2021 U.S. Dist. LEXIS 85347 (S.D. Cal. Feb. 25, 2021).

167. ALLELE BIOTECHNOLOGY AND PHARMACEUTICALS INC., https://www.allelebiotech.com

[https://perma.cc/74UK-M7UV] (last visited Oct. 24, 2021); see also Pfizer Gross Profit 2006-2021

| PFE, MARCOTRENDS, https://www.macrotrends.net/stocks/charts/PFE/pfizer/gross-profit [https://

perma.cc/JJA7-RL8T] (last visited Nov. 14, 2021) (Allele is a private corporation with $18M in



166 INDIANA HEALTH LAW REVIEW [Vol. 20:143

Pfizer in being first to market in the vaccine race—allowing it to immediately
secure $400 million in grants,168 an immediate multi-billion-dollar sales contract
with the U.S. Department of Health and Human Services and the Department of
Defense,169 and maintain leading revenues in continued vaccine sales.170 

Likewise, Regeneron used Allele’s mNeonGreen to be beat competitors to an
effective antibody therapeutic for those infected with SARS-CoV-2, helping it
capture over $2.59 billion in antibody-related revenue alone in just the second
quarter of 2021.171 Assigning a monetary value to that advantage may prove
difficult. If successful securing a verdict for infringement, Allele hopes to task a
jury with just such a difficult determination. What share of Regeneron’s profits
belong to Allele? As such, Regeneron is strongly motivated to secure a non-
infringement verdict. With the non-infringement so far denied, settlement
negotiations will surely be considered. However, if negotiations are unsuccessful,
the safe harbor issue is sure to arise again on appeal.

2. Benefit Of A Bright-Line Rule

In a word, the benefit of having a bright line rule in law is commonly noted
as predictability.172 In the same way detailed statutes and case law on corporations
offer value to business ventures seeking to organize as a corporation, a clear
interpretation of § 271(e)(1)’s “patented invention” would offer research tool
users and developers value. This clarity would add predictability to respective
liabilities and inform disputes prior to the cost of judicial involvement.
Information concerning liability, or the lack thereof, for use of research tools will
influence how researchers allocate resources for research and development. The

total funding from three investors while Pfizer regularly reports annual profits in excess of $30

billion).

168. Rebecca Tapscott, Regeneron, Pfizer and BioNTech Accused of Infringing Allele Patent

in Connection with COVID-19 Technologies, IPWATCHDOG (Oct. 7, 2020), https://www.

ipwatchdog.com/2020/10/07/regeneron-pfizer-biontech-accused-infringing-allele-patent-

connection-covid-19-technologies/id=126017/ [https://perma.cc/A9VD-58HG].

169. Pfizer and BioNTech Announce an Agreement with U.S. Government for Up to 600

Million Doses of mRNA-Based Vaccine Candidate Against SARS-CoV-2, BUSINESSWIRE (July 22,

2020), https://www.businesswire.com/news/home/20200722005438/en/ [https://perma.cc/M4AF-

2Z2D].

170. Kevin Dunleavy, Pfizer, Moderna Will Rake in a Combined $93 Billion Next Year on

COVID-19 Vaccine Sales: Report, FIERCE PHARMA (Oct. 18, 2021), https://www.fiercepharma.

com/pharma/pfizer-moderna-will-rake-a-combined-93-billion-next-year-covid-19-sales-says-

analytics-group [https://perma.cc/JJ6V-DX9S].

171. Kevin Dunleavy, Surprise COVID-19 Antibody Sales of $804M Help Regeneron Trounce

Expectations in Third Quarter, FIERCE PHARMA (Nov. 4, 2021), https://www.fiercepharma.

com/pharma/surprise-antibody-sales-804-million-help-regeneron-exceed-revenue-expectations-

third-quarter [https://perma.cc/3UJW-872X].

172. Bright-Line Rule, CORNELL L. SCH., https://www.law.cornell.edu/wex/bright-line_rule

[https://perma.cc/W5XA-WLL4] (last visited Oct. 23, 2021).



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 167

clearer the rule, the more efficient the outcome. The interpretation of § 271(e)(1)
needs a bright-line rule.

3. Danger Of A Bright-Line Rule

Why has the court been so reluctant to provide a bright-line rule on the status
of research tools under the safe harbor provision of § 271(e)(1)? First, bright-line
rules are often deemed mechanical, objective, and invariant. When applied across
all cases, mitigating factors or extenuating circumstances may be silenced,
underemphasized or ignored entirely–thus violating a sense of fairness in a given
outcome.173 Second, courts do not like to tie their own hands. A clear rule will
demand an outcome given some triggering fact pattern–regardless of an
unforeseen nuance the court would have rather weighted more heavily. Third, and
most relevant in the present instance, issuing a bright-line rule limiting statutory
language which appears broad to a judge requires reading more than the words
of the legislature–it often requires supposing intent of the legislature–anathema
to a strict textualist.174

4. A Conflict Between Courts

Another obstacle to the adoption of a bright line rule is the furthering of a
controversial influence of the Supreme Court on the country’s patent laws. Of
course, the Supreme Court has general subject matter jurisdiction and is superior
to the Federal Circuit. However, the Federal Circuit was specifically created to
resolve patent disputes and provide better predictability in patent law.175 To what
extent the Supreme Court should assert itself in reviewing the court specifically
designated to resolve patent disputes has been, and will continue to be, debated.

The Supreme Court has a habit of reversing the Federal Circuit on patent
cases, and has become increasingly active in doing so over the last twenty
years–reversing twenty two out of twenty seven cases between 2005 and 2015.176

With the vast majority of reversals favoring an alleged infringer, it is not
surprising the Supreme Court is considered hostile to patent holders; the Federal
Circuit is notably more likely to uphold the validity of a patent.177 Though the
Supreme Court is the highest authority in United States patent law, it has a

173. Id.

174. See Merck KGaA, 545 U.S. at 202, 206 (Justice Scalia’s aversion to “read narrowly”

where the statutory text “provides a wide berth” is both illustrative in general and captures the issue

in the context of this exact statute).

175. CONG. RESEARCH SERV., PATENT LAW AND INNOVATION: THE CREATION, OPERATION

AND A TWENTY-YEAR ASSESSMENT OF THE U.S. COURT OF APPEALS FOR THE FEDERAL CIRCUIT 1

(2003).

176. OSHA BERGMAN WATANABE BURTON, Why Does the U.S. Supreme Court Keep

Reversing the Federal Circuit? (Mar. 31, 2017), https://www.obwbip.com/newsletter/why-does-

the-u-s-supreme-court-keep-reversing-the-federal-circuit [https://perma.cc/9XB3-QJE2].

177. Id.



168 INDIANA HEALTH LAW REVIEW [Vol. 20:143

limited docket for reviewing patent cases and the Federal Circuit generally has
the final word on all but a handful178 of the roughly 450 cases decided annually.179

As such, though speculation often erupts with any Supreme Court decision
perceived as threatening the enforceability of patents, as in Merck,180 concern is
generally quelled shortly thereafter by the less rigid and more patent-holder-
friendly, application by the Federal Circuit. With a practical limit on case-by-case
enforcement, the threat of undesirable rigidity, and a tendency for the federal
circuit to ameliorate resultant rules, might a bright line rule from the Supreme
Court quickly become blurry? To answer this question with any persuasiveness
will require unfolding the proposed rule–which will now be explained quite
simply.

5. The Proposed Resolution

The Supreme Court, potentially in response to these cases, should enunciate
a rule ensuring the enforceability of patents directed at research tools. The
defining characteristic of this class of inventions is that they are not themselves
subject to FDA approval. Hence, the safe harbor of § 271(e)(1) should not apply
to research tools and strict symmetry between § 156 and § 271(e)(1) should be an
unambiguous requisite for shielding under the safe harbor.

It is this author’s position that a bright line rule from the Supreme Court on
this issue would not be subject to typical vulnerabilities or ineffectual application
in the lower courts. Initially, with respect to the rigidity of the rule, the concern
surrounding a harmful mechanical application is quelled due to the nature of the
players in this industry. Those made subject to liability after any narrowing of the
safe harbor are largely sophisticated players with a close eye on this very topic.
A word of warning would spread rapidly through a tight community of highly
skilled research professionals. This warning would allow them to quickly license
their use of equipment belonging to a now emboldened patent holder or seek an
alternative technology. Those affected know they are affected and generally have
suitable resources to respond.

Beyond the parties affected, a second factor strongly supporting the success
of a bright line rule in this case relates to the nature of the rule itself. Formally
recognizing the criteria of FDA approval calls for an objective test which is
resolved through a purely factual inquiry. There is no heavy lifting required by
courts to expand upon the ‘reasonableness’ standard.

178. Devin Salmon, A Sign of the Times? A Brief Look at the Trend of Patent Cases Before

the US Supreme Court, IP.COM, https://ip.com/blog/a-sign-of-the-times-a-brief-look-at-the-trend-

of-patent-cases-before-the-us-supreme-court/ [https://perma.cc/G8NT-LHJH] (last visited Oct. 22,

2021) (though the Supreme Court has averaged just one or two patent cases per year over the last

80 years, it has roughly tripled this average over the last 10 years).

179. Dan Bagatell, Fed. Cir. Patent Decisions in 2019: An Empirical Review, LAW360 (Jan.

9, 2020), https://www.law360.com/articles/1232623/fed-circ-patent-decisions-in-2019-an-

empirical-review [https://perma.cc/E8TY-F9JA].

180. See supra note 26 and accompanying text.



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 169

A third factor forecasting the success of the rule relates to the dynamic
between the Supreme Court and the Federal Circuit. Simply put, the rule would
generally support patent enforceability and be favored in its most simple form at
the Federal Circuit. Further, if a desire to alter the rule arose, there is little nuance
to leverage.

With two recent controversies emerging in jurisdictions having uncertain
precedent, historical revenues at stake, and plenty of interested money available
for advocacy, the Supreme Court should consider resolving these cases with a
landmark decision of clarity. As far as the safe harbor is concerned, there is
disagreement and ambiguity on specialized doctrine. Whether research tools fall
under the safe harbor is a matter lower courts can manipulate by selective use of
precedent. This yields uncertainty, expense, and potentially fosters bad faith in
competition.
Alternatively–and indeed the most direct means of clarification–would be for the
legislature to take unilateral action. A sufficient action from the legislature would
consist of merely an exchange of the term “patented invention” in § 271 for the
§ 156 “product” and it’s associated definition.181 With decades of this debate as
context, and § 156’s explicit definition of “product”–being limited to articles
subject to FDA approval182 –this would result in a clear understanding and
virtually immediate predictability among courts.  

C. The Scope Of Relevance

1. Illustrative Importance of Research Tools

i) MOLECULAR BIOMARKERS

Much of the litigation discussed centers on this class of research tools, but
why are they important? As has been explained, mNeonGreen and other
fluorescent proteins are considered “marker” or “indicator” proteins. In the case
of vaccine research, they annunciate the existence of antibodies successfully
produced during clinical trials of vaccines or similar activities. More generally,
molecular biomarkers are used to “diagnose disease, monitor disease progression
and response to therapy, and are targets for development of new drugs.”183

Generally, these biomarkers are not subject to FDA approval since they are not
administered to patients. A lack of patent protection for molecular biomarkers
would allow uncompensated use and copying in a majority of their
applications–reducing both the value of the inventions and investment in the
technology.

181. § 156(f).

182. Id.

183. KECK GRADUATE INST., About the Center for Biomarker Research, https://www.kgi.edu/

faculty-and-research/centers-initiatives/center-for-biomarker-research/ [https://perma.cc/TLF3-

7Y5Q] (last visited Oct. 24, 2021).



170 INDIANA HEALTH LAW REVIEW [Vol. 20:143

ii) MEDICAL LABORATORY DEVICES

Medical devices used as research tools are more intuitive and are indeed
ubiquitous. From laboratory microscopes to centrifuges, this class of tools is
interacted with in a high-school science classroom and the occasional visit to the
general practitioner. Some of these devices are subject to FDA approval, such as
a cardiac defibrillator, and in that sense, do not fall within the typical definition
of a research tool. Generally, devices used in laboratory settings are not subject
to FDA approval and would be at risk of losing patent protection if research tools
were widely included in the ambit of § 271(e)(1). A loss of commercial value in
the development of new and improved laboratory equipment, by the
unencumbered copying by competing manufacturers, would diminish the
investment in this industry and reduce published technological advances.

iii) ARTIFICIAL INTELLIGENCE

One technology often classified as a research tool is artificial intelligence
(AI). For AI to be patentable it must do more than perform mathematical
formulas, mental processes, or organize ordinarily human activity.184 Even so,
thousands of AI related patents have met that burden and have been granted. The
growth of AI patents in the medical industry has experienced rapid acceleration
since 2011 due to a significant increase in big data analytics and improvements
in computing power.185 Patents on AI research tools–especially those mining and
predicting usefulness of the astronomical number of uncharted chemical
compounds–will become increasingly contentious as the space gets crowded.186

For prospective investors, it will be increasingly important to understand the issue
of AI as research tools under patent protection prior to entering into this new era.
AI is particularly vulnerable to copying as it is often, in large part, code which is
run on a supercomputer.

2. Importance Of Patent Protection

Whether the right to exclude extends to lawfully patented research tools must
be clearly answered in the affirmative to secure current investment, and promote
future investment, in the above industries of public import. If a patented research
tool, requiring a large capital investment, can be used without compensation

184. Andrew Rapacke, Are Machine Learning Algorithms Patentable?, RAPCKE L. GRP. (Jan.

27, 2020), https://arapackelaw.com/patents/softwaremobile-apps/are-machine-learning-algorithms-

patentable/ [https://perma.cc/JAX2-VY5V].

185. Yang Xin et al., The Development Trend of Artificial Intelligence in Medical: A

Patentometric Analysis, (1) A.I LIFE SCI. 100006 (2021).

186. Sam Lemonick, Exploring Chemical Space: Can AI Take Us Where No Human Has Gone

Before?, CHEM. & ENG’G NEWS (Apr. 6, 2020), https://cen.acs.org/physical-chemistry/

computational-chemistry/Exploring-chemical-space-AI-take/98/i13 [https://perma.cc/2WTZ-

2MAE].



2023] THE SAFE HARBOR OF 35 U.S.C. § 271(e)(1) 171

under a negotiated licensing agreement, why should companies like Allele invest
in producing fluorescent proteins capable of accelerating the development of
future vaccines? Though Allele could use the technology internally, Allele
generates a large part of its revenue from producing and selling cutting edge
technology for clinical and therapeutic use and develops an array of research
tools.187

A second consequence of limiting enforceability of research tool patents is
that fewer patents will be issued on research tools commonly used in generating
data for FDA approval. This will discourage public disclosure of available
technology for research tools and preclude possible advancements thereupon.
Rather, developers of research tools may elect for keeping trade secrets.
Protecting the trade secrets may needlessly complicate experiments required to
generate data for the FDA or limit where the experiments may be conducted.
These outcomes would slow the progress of valuable technologies.  

Some may argue an exception should be carved out for the case where a
patented research tool is the exclusive option for obtaining specific data required
for FDA approval. If the holder of the patent on the research tool and the patent
on the drug are one and the same, the owner could conceivably delay FDA
approval by withholding the required patented research tool, thus extending their
monopoly. This reasoning is not persuasive and fails to consider existing
processes and procedures. Such an exception is not required because the research
tool may be properly licensed by the generic. If the holder is unwilling, a case for
mandatory licensing may be considered under those rare circumstances.
Nullifying the patent amounts to taking property rights promised by the
Constitution188 and otherwise does not advance the state of science.

IV. CONCLUSION

Any ambiguity in a statute is properly presumed a legislative failure. As such,
the duty to remove alternative readings and denounce misconceived case law rests
first with the legislature. Adopting symmetric language and definitions between
§ 156 and § 271 of the Act would resolve the ambiguity faced by Federal District
Courts and prospective litigants. While an amendment from the legislature is the
preferable solution, the Supreme Court must not be idle while opposing
interpretations leave an issue essentially without law.

If the remaining Allele case is eventually appealed to the Supreme Court, the
Court should enunciate an interpretation of Merck and § 271 which explicitly
excludes patented inventions not themselves subject to FDA approval. The
Supreme Court should clarify that research tools are not within the purview of §
271(e)(1) and clarify that the “product” of §156 has the same scope as the
“patented invention” of § 271. While the judiciary is not licensed to write laws,
and the nation admires judicial humility, the duty to interpret is of particular

187. Second Amended Complaint at 4, Allele Biotechnology & Pharm., Inc. v. Regeneron

Pharm’s, Inc., No. 20-cv-08255, 2021 WL 2880694 (S.D.N.Y Apr. 8, 2021).

188. U.S. CONST. art. I, § 8 cl. 8.



172 INDIANA HEALTH LAW REVIEW [Vol. 20:143

importance when ambiguity has resulted in inconsistent application of the patent
laws. Poorly worded statutes need not beget murky interpretations. Whether a
particular use of a patented invention in the United States is patent infringement
should not depend on which federal district one lives within.