STRATTERA – DIVERGENT
RESULTS IN CANADA AND
THE UNITED STATES
April 4, 2012
Patrick S. Smith
DIVERGENT RESULTS
• As will be discussed in STRATTERA, for all practical purposes
the findings of fact and relevant statutory sections are the same in
Canada and the United States
• The patents at issue claim the use of atomoxetine hydrochloride
for use in the treatment of ADHD
• The United States application was filed before the results of a
clinical trial was received by the patentee – the U.S. Patent was
found to be valid
• The positive clinical trial results were received before the
Canadian application was filed – yet the Canadian Patent was
found to be invalid
2
RESULTS OF VALIDITY CHALLENGES
U.S. Trial Decision
Patent invalid for something the Trial Judge refers to as “lack of enablement/utility”
Eli Lilly and Co. v. Actavis Elizabeth LLC et al., 731 F. Supp. 2d 348 (D.N.J. 2010)
U.S. Court of Appeal for the Federal Circuit
Trial decision overturned
Disclosure sufficient
Invention has utility
Eli Lilly and Co. v. Actavis Elizabeth LLC et al., Appeal No. 2010-1500 (Fed. Cir. July 29, 2011)
Canadian Trial Decision
Not enough testing to demonstrate long term clinical effectiveness
Patent invalid for want of disclosure of sound prediction
Novopharm v. Eli Lilly and Co., 2010 FC 915, 87 C.P.R. (4th) 301
Canadian Appeal Decision
Upholds trial decision
Eli Lilly and Co. v. Teva Canada Ltd. (formerly known as Novopharm Ltd.), 2011 FCA 220, 94 C.P.R. (4 th)
95
3
BACKGROUND ON ADHD
• ADHD is a complex, chronic and inheritable neurobiological disorder that is characterized by a
developmentally inappropriate level of inattention, hyperactivity and impulsiveness.
• The prevalence of ADHD is about three to five percent in school-age children. Up to 60% of
patients with childhood ADHD carry symptoms into adulthood.
• Academic achievement is often impaired, leading to conflict with family and school authorities.
Familial relationships are often strained because parents believe that the afflicted child’s
troublesome behaviour is willful.
• Symptoms of hyperactivity in adults include holding multiple jobs, difficulty in participating in
sedentary activities, and avoiding jobs and hobbies that provide limited opportunity for constant
motion.
U.S. Trial Decision – p. 5
4
KNOWN TREATMENTS FOR ADHD
• No cure but symptoms can be ameliorated
• Stimulants
- controlled substances (diversion/substance abuse potential)
- not effective for all patients
- in early 1990’s, no sustained release version
- stigma including principal office visits
• Tricyclic Antidepressants
- not as effective as stimulants
- in early 1990’s, desipramine implicated in sudden death of some children
U.S. Trial Decision, pp. 6, 16, 25
Canadian Trial Decision, pp. 6, 21-22
• Lilly’s Strattera atomoxetine hydrochloride was the first non-stimulant ADHD drug
approved by the FDA and Health Canada
5
THE STRATTERA ATOMOXETINE HYDROCHLORIDE STORY
• Atomoxetine first synthesized by Lilly scientists around 1980
• Throughout the 1980’s, Lilly conducted clinical studies on the use of atomoxetine in the
treatment of depression
• The totality of these clinical trials lead to the abandonment of atomoxetine for use in
depression
• These Lilly studies (mostly unpublished) did show that atomoxetine was well tolerated by
patients
U.S. Trial Decision, p. 51
Canadian Trial Decision, pp. 7-8
6
ATOMOXETINE AND ADHD
• Two Lilly scientists conceived that atomoxetine may be effective in the treatment of ADHD
• One of the Lilly scientists, Dr. Heiligenstein (a child psychiatrist) approached leading ADHD
researchers (Spencer and Biederman) at the Massachusetts General Hospital (teaching
hospital associated with Harvard) and asked that MGH run an ADHD study with atomoxetine
• Lilly funded the study, provided atomoxetine and placebo and allowed MGH access to Lilly’s
confidential FDA filings for the purpose of running the study
US Appeal Decision, pp. 5-6
Canadian Trial Decision, p. 8
7
CHRONOLOGY OF THE MGH STUDY AND LILLY’S PATENT
APPLICATIONS
•
December 1, 1994, MGH submits Investigational New Drug (IND) application to the FDA
•
January 3, 1995, FDA approval for study (MGH IRB approval also obtained about this time)
•
January 11, 1995, Lilly files US patent application that results in U.S. Patent No. 5,658,590 (the ‘590 Patent)
•
May 1995, positive results from MGH Study were reported to Lilly
•
October 1995, positive results reported by MGH researchers at the world’s largest meeting of ADHD
practitioners (American Association of Child and Adolescent Psychiatry (AACAP)
•
January 4, 1996, Canadian patent application filed that results in Canadian Patent No. 2,209,735 (the ‘735
Patent)
U.S. Trial Decision, pp. 52-53
U.S. Appeal Decision, pp. 5-6
8
THE MGH STUDY
•
22 adult ADHD patients enrolled – 21 completed study
• Double-blind, placebo-controlled, cross-over evaluation
•
3 week treatment arms with a one week washout
•
Assessment included standardized patient interviews and other neuropsychological tests
•
Overall response rate for ADHD symptoms was clinically and statistically higher during atomoxetine treatment
than during placebo (53% v. 10.5%; p.0.05)
Canadian Trial Decision, pp. 10-11
U.S. Trial Decision, p. 53
9
OCTOBER 1995 – AACAP ABSTRACT
Objective:
The assessment of an experimental, highly noradrenergic
antidepressant tomoxetine as an alternative treatment for adult attentiondeficit/hyperactivity disorder (ADHD). Method: This was a double-blind,
placebo-controlled, crossover study of tomoxetine in well-characterized adults
with ADHD attending to issues of psychiatric comorbidity. Results: Treatment
with tomoxetine at an average oral daily dose of 76 mg/day was well tolerated.
The overall response rate for ADHD symptoms was clinically and statistically
higher during tomoxetine treatment than during placebo (53% vs. 10.5%; p<
0.05). There was a highly significant drug by time interaction (z = 3.4, p = 0.001)
in the reduction in ADHD symptoms that was robust enough to be detectable in
a parallel groups comparison during the first four weeks of the protocol (z = 3.1,
p = .002). Conclusions: This preliminary study has shown that tomoxetine
significantly improved ADHD symptoms and was well tolerated.
10
THE DISCLOSURE IN STRATTERA PATENTS
• The disclosure and claims of the US ‘590 and CDN ‘735 Patents are virtually the
same
• The patents disclose that atomoxetine is effective in all forms of ADHD in children,
adolescents and adults
• Improved safety profile of atomoxetine is disclosed
• Recommended dosing is provided
• The truthfulness of the above is not disputed in either Canada or the U.S. invalidity
proceedings
• Details or results of MGH Study are not provided in the patent disclosures
11
RESULTS OF VALIDITY CHALLENGES
U.S. Trial Decision
Patent invalid for something the Trial Judge refers to as “lack of enablement/utility”
Eli Lilly and Co. v. Actavis Elizabeth LLC et al., 731 F. Supp. 2d 348 (D.N.J. 2010)
U.S. Court of Appeal for the Federal Circuit
Trial decision overturned
Disclosure sufficient
Invention has utility
Eli Lilly and Co. v. Actavis Elizabeth LLC et al., Appeal No. 2010-1500 (Fed. Cir. July 29, 2011)
Canadian Trial Decision
Not enough testing to demonstrate long term clinical utility
Patent invalid for want of disclosure of sound prediction
Novopharm v. Eli Lilly and Co., 2010 FC 915, 87 C.P.R. (4th) 301
Canadian Appeal Decision
Upholds trial decision
Eli Lilly and Co. v. Teva Canada Ltd. (formerly known as Novopharm Ltd.), 2011 FCA 220, 94 C.P.R. (4 th)
95
12
SIMILAR STATUTORY PROVISIONS
UTILITY
• United States
“Whoever invents or discovers any new and useful process, machine,
manufacture, or composition of matter, or any new and useful improvement
thereof, may obtain a patent therefor, subject to the conditions and requirements
of this title.”
35 U.S.C. §101
• Canada
“invention” means any new and useful art, process, machine, manufacture or
composition of matter, or any new and useful improvement in any art, process,
machine, manufacture or composition of matter;”
c. P-4, R.S.C. 1985 s. 2
13
SIMILAR STATUTORY PROVISIONS
ENABLEMENT/DISCLOSURE
• United States
The specification shall contain a written description of the
invention, and of the manner and process of making and using it,
in such full, clear, concise, and exact terms as to enable any
person skilled in the art to which it pertains, or with which it is
most nearly connected, to make and use the same, and shall set
forth the best mode contemplated by the inventor of carrying out
his invention.
35 U.S.C. § 112
14
SIMILAR STATUTORY PROVISIONS
ENABLEMENT/DISCLOSURE
• Canada
The specification of an invention must
(a) correctly and fully describe the invention and its operation
or use as contemplated by the inventor;
(b) set out clearly the various steps in a process, or the
method of constructing, making, compounding or using a
machine, manufacture or composition of matter, in such full,
clear, concise and exact terms as to enable any person skilled
in the art or science to which it pertains, or with which it is
most closely connected, to make, construct, compound or use
it;
Patent Act, c. P-4, R.S.C. 1985, s. 27(3)
15
WHY DID THE RESULTS DIFFER
1. The information regarding utility that must be
disclosed in a patent
2. Different dates for determining utility
3. How the Usefulness of an invention is determined
- Promise of Patent / Utility Standards
16
1. What Information Regarding Utility Must be Disclosed in a Patent
U.S. Trial Division (p. 60)
• Trial Judge referred to this part of decision as “lack of enablement/utility”
• Because the ‘590 Patent did not disclose test results showing that atomoxetine
could be used to treat ADHD and because a person of ordinary skill would not
have recognized the claimed method’s utility in light of the specification, the
patent was not properly enabled contrary to 35 U.S.C. § 112
17
1. What Information Regarding Utility Must be Disclosed in a Patent
U.S. Court of Appeals for the Federal Circuit
• The first paragraph of § 112 requires nothing more than objective enablement
• The ‘590 Patent describes and enables the utility of atomoxetine to treat
ADHD
In the case of atomoxetine, however, the norepinephrine relationship was known,
safety for antidepressant activity had been established, the specification contained a
full description of the utility, experimental verification had been obtained before the
patent was granted, and the examiner had not requested additional information.
There was no evidence that the disclosure is “on its face, contrary to generally
accepted scientific principles.”
U.S. Appeal Decision, p. 17
18
1. What Information Regarding Utility Must be Disclosed in a Patent
Canadian Trial and Appeal Decisions
• If patent’s utility is based upon demonstrated utility, patent must provide
sufficient disclosure to allow a person skilled in the art to make and use the
invention (this requirement was set by the ‘735 Patent)
• However, because the invention of the ‘735 Patent was based upon a sound
prediction (because long term clinical trials had not been conducted) the
patent needed to disclose the factual basis and line of reasoning for the
prediction which would include disclosing the results of the MGH Study.
Canadian Trial Decision, pp. 68-72
Canadian Appeal Decision, pp. 14-16
19
2. What is the Appropriate Date for Determining Utility
• Important issue because results of the MGH Study not received by Lilly until after U.S. patent
application filed
U.S. Trial Division, p. 55
• Enablement or utility is determined as of the application filing date
U.S. Court of Appeals for the Federal Circuit, p. 16
When priority is not at issue, generally the applicant may provide data obtained either
before or after the patent application was filed. With reference to demonstration of utility,
in Brana, 51 F.3d at 1567 n.19 the court noted that post-filing evidence “can be used to
substantiate any doubts as to the asserted utility since this pertains to the accuracy of a
statement already in the specification.” Here the utility of tomoxetine is accurately stated in
the specification; there is no allegation of falsity in the disclosed utility, and the patent
examiner did not require the presentation of additional data.
20
2. What is the Appropriate Date for Determining Utility
Canada
• The Canadian filing date is the relevant date for determining utility
but additional disclosure obligations may arise depending upon
how utility is characterized (demonstrated/soundly predicted)
21
3.
What Does it Mean for an Invention to be Useful
• In both Canada and the United States, if a claimed invention does
not work at all, it is said to be inoperable and the claim will be
invalidated for want of utility
United States
• If a credible utility is disclosed and there is no finding of
inoperability, a patent will not be invalidated for inutility
22
3.
What Does it Mean for an Invention to be Useful
Canada
• In addition to inoperability, a utility analysis will be measured by
reference to the “promise of a patent”
• If there is no promise of utility disclosed, a scintilla of usefulness
will suffice
• If, however, a Court discerns a promise of utility (when the
specification is viewed through the perspective of a person skilled
in the art) usefulness will be measured by reference to the
promise
23
3.
What Does it Mean for an Invention to be Useful
• If the patentee has demonstrated the utility of the promise, no
non-statutory disclosure obligations arise
• If the patent’s utility is based upon sound prediction, the patent
must also disclose the factual basis and sound line of reasoning
for the prediction. For the ‘735 Patent (implied promise of long
term usefulness), the results of the MGH Study were required to
be disclosed
• Thus, the disclosure obligations of a patentee in Canada may
only be known after the Court construes the promise of the patent
24
Policy Considerations
• Disclosure
- The relatively objective statutory enablement or disclosure standards
increase certainty in patent systems
- Coupling disclosure obligations to characterization of how utility is
shown needlessly introduces subjectivity and uncertainty into patent
disputes
- If a patent discloses a new, unobvious and useful invention and
provides sufficient information to allow a person of skill to make and
use an invention, there is sufficient consideration for the grant of a
patent
25
Policy Considerations
• Relevant Utility Dates
- Patent applicants should not be rewarded for pure guesses
- If an applicant provides sufficient disclosure with a credible utility, a
patent should only be invalidated if the invention is inoperable
- This encourages early disclosure of useful inventions and gives effect
to the presumption of validity
26
Policy Considerations
• Utility Standards
- Anything that isn’t useless is useful
- “Scintilla” or “Not Devoid of Utility” should be the threshold standard
for utility
- Increasing the utility standards by reference to a promise of the patent
discourages applicants from discussing the attributes of their
invention for fear of being held to a higher utility standard
27
Thank You
PATRICK S. SMITH
COMPARATIVE INTELLECTUAL
PROPERTY LAW SYMPOSIUM
APRIL 4, 2012
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