United States Court of Appeals for the Federal Circuit
2009-1350
ALZA CORPORATION
and MCNEIL-PPC, INC.,
Plaintiffs-Appellants,
v.
ANDRX PHARMACEUTICALS, LLC
and ANDRX CORPORATION,
Defendants-Appellees.
Constantine L. Trela, Jr., Sidley Austin LLP, of Chicago, Illinois, argued for
plaintiffs-appellants. With him on the brief were David T. Pritikin; Jeffrey P. Kushan,
Todd A. Wagner and Peter S. Choi, of Washington, DC.
C. Kyle Musgrove, Kenyon & Kenyon LLP, of Washington, DC, argued for
defendants-appellees. With him on the brief were John W. Bateman and Robert F.
Vroom.
Appealed from: United States District Court for the District of Delaware
Judge Joseph J. Farnan, Jr.
United States Court of Appeals for the Federal Circuit
2009-1350
ALZA CORPORATION
and MCNEIL-PPC, INC.,
Plaintiffs-Appellants,
v.
ANDRX PHARMACEUTICALS, LLC
and ANDRX CORPORATION,
Defendants-Appellees.
Appeal from the United States District Court for the District of Delaware in case no. 05-
CV-642, Judge Joseph J. Farnan, Jr.
__________________________
DECIDED: April 26, 2010
__________________________
Before DYK, SCHALL, and PROST, Circuit Judges.
PROST, Circuit Judge.
ALZA Corporation and McNeil-PPC, Inc. (collectively, “ALZA”) appeal from a final
decision of the United States District Court for the District of Delaware. Following a
bench trial, the district court found the patented treatment methods of U.S. Patent No.
6,919,373 (“’373 patent”) nonobvious, but held the asserted claim both not infringed and
invalid for lack of enablement. We affirm because we conclude that the asserted claims
of the ’373 patent are invalid for lack of enablement.
BACKGROUND
The ’373 patent claims methods for treating primarily Attention Deficit and
Hyperactivity Disorder (“ADHD”) through a methylphenidate (“MPH”) drug dosage form
that has an ascending release rate over an extended period of time. The ’373 patent
application, filed in 1999, claimed priority to provisional application No. 60/031,741
(“’741 application”), filed on November 25, 1996, and the earliest non-provisional
application No. 08/910,593 (“’593 application”), filed on July 31, 1997.
Before the claimed invention, ADHD had been treated with other oral drugs, the
most common of which, Ritalin®, was an immediate-release (“IR”) formulation of MPH.
This formulation releases the drug within minutes and treats the symptoms for three to
five hours. As a result, such prior drug treatments were taken two or three times a day.
As many patients who take ADHD medication are children, they took one dose before
school and one or two additional doses about four to five hours apart, at least one of
which was administered at school. Thus, a once-a-day method of treating ADHD
offered the potential of reducing patient-compliance problems that resulted from the
need for treatment during the school day.
At the time of the invention, it was well known how to develop sustained-release
dosage forms, also known as “controlled release” or “extended release.” Designed to
release the drug at a constant rate, sustained-release dosage forms typically provided
the desired steady therapeutic effect. It was also known that sustained-release dosage
forms could exhibit descending or ascending release rates by manipulating the methods
and materials used to produce the dosage forms.
After a series of clinical studies, ALZA determined that MPH plasma
concentrations that had ascending patterns provided greater efficacy for treating ADHD
than concentrations that were constant. Using this knowledge, ALZA developed safe
and effective once-a-day extended release oral dosage forms that could deliver MPH
2009-1350 2
with the ascending release pattern. Admittedly, the bulk of ALZA’s efforts went into
developing an osmotic dosage form, which uses a compartment containing drug and
various osmotic excipients.
ALZA subsequently filed its patent applications. Claim 1, the only independent
claim implicated on appeal, of the ’373 patent claims:
A method for treating ADD or ADHD comprising administering a dosage
form comprising methylphenidate that provides a release of
methylphenidate at an ascending release rate over an extended period of
time.
’373 patent col.23 ll.12–15 (emphasis added). The specification focuses on how
osmotic systems can be adapted to create an ascending release dosage form to treat
ADHD. The specification also mentions non-osmotic dosage forms. Id. at col.3 ll.53–
62. 1
ALZA markets and sells a product called CONCERTA®, which embodies the
claimed invention; upon ingestion, it releases the drug at an ascending rate for an
extended period of time, as required by claim 1. ALZA’s competitors, Andrx
Pharmaceuticals, LLC and Andrx Corporation (collectively, “Andrx”), produce a product
pursuant to an approved Abbreviated New Drug Application (“ANDA”). Like
1
Osmotic dosage forms are dosages with a “push” layer comprising
osmotically effective solutes—i.e., substances that dissolve and, as fluid is imbibed
through the semipermeable pill wall, swell and push against the deliverable drug
formulation. The pill wall is semipermeable, meaning that it is permeable to the
passage of external fluids into the compartment, but is substantially impermeable to the
passage of a drug agent or excipients outward. The drug itself exits via an orifice,
which constitutes the “passageway” through the wall for delivering the drug from the pill,
so as to gradually increase drug concentration in the body.
Non-osmotic dosage forms within the scope of the claims include “oral tablets
and capsules” with sustained-release dosage forms suitable for producing ascending
release rates, where the release rate is as determined by an appropriate in-vitro
dissolution test. Non-osmotic dosage forms do not have a “push” layer.
2009-1350 3
CONCERTA®, Andrx’s product has an outer IR coating around a sustained-release
inner core. In 2005, ALZA sued Andrx, alleging infringement of the ’373 patent and U.S.
Patent No. 6,930,129 (“’129 patent”). 2 Andrx denied that its products infringed the
patents. It also asserted affirmative defenses, alleging that the ’373 patent was invalid
because it was obvious and not enabled, and counterclaimed for a declaratory judgment
of noninfringement and invalidity of the asserted claims of the ’373 patent.
The district court held a Markman hearing on the construction of various terms in
dispute. In rejecting Andrx’s attempt to limit the scope of the claim to osmotic dosage
forms, the court construed the phrases “pharmaceutically acceptable composition” and
“dosage form” to mean “a pharmaceutical composition that includes a dose of
methylphenidate,” which includes non-osmotic dosage forms, as ALZA requested. 3
Alza Corp. v. Andrx Pharms., LLC, No. 05-642, at 2 (D. Del. Oct. 5, 2007) (order on
claim construction). Further, the court construed the disputed term “an ascending
release rate over an extended period of time” to mean:
a release of methylphenidate from the dosage form wherein the amount
released in a periodic interval is increased over the amount released
during the immediately preceding periodic, interval starting at t=0 and
continuing through at least the mid-point of the T90 and for at least three
hours. The release rate is determined by an appropriate in-vitro
dissolution test. The ascending release rate does not include release of
2
On the first day of the bench trial, ALZA moved to dismiss its claims
relating to the ’129 patent with prejudice. J.A. 12535. The district court dismissed
Andrx’s declaratory judgment counterclaims regarding the ’129 patent without prejudice
for lack of jurisdiction. Alza Corp. v. Andrx Pharms., LLC, 607 F. Supp. 2d 614, 624 (D.
Del. 2008). The ’129 patent is therefore not at issue in this appeal.
3
Neither party challenges the district court’s finding that claim 1 includes
both osmotic and non-osmotic dosage forms.
2009-1350 4
drug from any immediate-release drug coating that may be applied to the
dosage form. 4
Id.
Following a bench trial, the district court determined that the ’373 patent was not
infringed. The district court concluded that claim 1, as construed, “require[s] release of
non-IR MPH during the initial interval of an appropriate dissolution test.” Alza, 607 F.
Supp. 2d at 624. According to the district court, there was substantial evidence that “the
amount of [MPH] released [by Andrx’s product] in the first hour of the dissolution test is
all attributable to the IR portion of methylphenidate,” which ALZA failed to adequately
rebut. Id. at 628–31. The district court also found the asserted claims of the ’373 patent
not obvious.
The district court, however, concluded that the asserted claims are invalid for
lack of enablement because the specification does not enable the full scope of claim 1,
which covers both osmotic and non-osmotic dosage forms. Before the district court, the
parties agreed that the specification enables osmotic oral dosage forms, but disputed
whether it also enables non-osmotic oral dosage forms. While the court found that the
claim includes non-oral as well as oral dosage forms, it concluded that it could resolve
the enablement dispute between the parties in Andrx’s favor solely by looking to non-
osmotic oral tablets and capsules. As a result, it explained that the enablement issue
reduces to factual considerations with regard to whether undue experimentation is
required to make oral dosage forms other than osmotic dosage forms that meet the
limitations of the claims. Applying the factors set forth in In re Wands, 858 F.2d 731,
4
Before the district court and on appeal, the parties dispute whether the
inner core, which releases MPH over an extended time period, infringes the ’373 patent.
2009-1350 5
735 (Fed. Cir. 1988), 5 the district court found that developing non-osmotic oral dosage
forms, such as tablets and capsules, as claimed requires undue experimentation. Alza,
607 F. Supp. 2d at 651–59. Accordingly, the district court determined that the asserted
claims are not enabled and thus invalid.
ALZA timely appeals. We have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
DISCUSSION
On appeal, ALZA argues that the district court erred in finding claim 1 invalid for
lack of enablement. The parties agree that the claim construction adopted by the
district court requires the enablement of both osmotic and non-osmotic dosage forms
and they also agree that osmotic dosage forms are enabled. The dispute is whether the
specification would have enabled a person of ordinary skill in the art to create non-
osmotic oral dosage forms—namely, tablets and capsules—with ascending release
rates without undue experimentation at the time of filing. 6
ALZA asserts that creating non-osmotic dosage forms and manipulating their
release rates was well known to a person of ordinary skill in the art at the time the ’373
patent application was filed. In addition, ALZA argues that the specification provides
sufficient guidance regarding non-osmotic dosage forms because it identifies a variety
5
The factors are: “(1) the quantity of experimentation necessary, (2) the
amount of direction or guidance presented, (3) the presence or absence of working
examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative
skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the
breadth of the claims.” Wands, 858 F.2d at 737.
6
ALZA also argues that the claimed non-osmotic dosage forms should be
limited to oral dosage forms and exclude non-oral dosage forms. We need not resolve
this issue, however, because we agree with the district court that non-osmotic oral
dosage forms are not enabled.
2009-1350 6
of suitable non-osmotic dosage forms and cites to a portion of a standard text to explain
how to make and use such non-osmotic, sustained-release dosage forms with
experimentation. ALZA concedes that even with the guidance provided in the
specification, a person of ordinary skill in the art would be required to engage in an
iterative, trial-and-error process to practice the claimed invention; however, it disputes
that the amount of experimentation required is undue. Instead, ALZA argues that non-
osmotic dosage forms with ascending release rates could be made with only routine
effort by those skilled in the art because the methods and materials used to produce
dosage forms with constant, descending, or ascending release rate profiles are
essentially the same and well known.
Andrx disputes ALZA’s contention that enablement can be satisfied by referring
to what persons of ordinary skill would know because what one of the proper skill in the
art knows cannot substitute for disclosure of novel aspects of the invention, i.e., the
non-osmotic dosage forms exhibiting ascending release rates. Further, Andrx argues
that the evidence presented at trial indicates that even one skilled in the art would find it
difficult to develop a non-osmotic dosage form exhibiting an ascending release rate,
particularly in light of the sparse guidance provided in the specification. Andrx asserts
that the district court’s factual findings that making a non-osmotic dosage form would
require undue experimentation were not clearly erroneous, but rather, supported by the
record. Andrx points to three Wands factors in particular—the guidance provided by the
specification, the presence or absence of working embodiments, and the breadth of the
claims—and submits that they strongly weigh in favor of a finding that creating non-
osmotic dosage forms with ascending release rates requires undue experimentation.
2009-1350 7
Upon review of the record, we agree with Andrx that the district court was correct in
concluding that the asserted claims are invalid for lack of enabling non-osmotic oral
dosage forms with ascending release rates.
We begin with the statute. The enablement requirement is codified in 35 U.S.C.
§ 112, ¶ 1, which 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.
Enablement is determined as of the effective filing date of the patent’s application. See
Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1371–72 (Fed. Cir. 1999). “To be
enabling, the specification of a patent must teach those skilled in the art how to make
and use the full scope of the claimed invention without ‘undue experimentation.’”
Genentech Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In
re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)). “Whether undue experimentation
would have been required to make and use an invention, and thus whether a disclosure
is enabling under 35 U.S.C. § 112, ¶ 1, is a question of law that we review de novo,
based on underlying factual inquiries that we review for clear error.” See Enzo
Biochem, 188 F.3d at 1369. Because patents are presumed valid, lack of enablement
must be proven by clear and convincing evidence. See Auto. Tech. Int’l, Inc. v. BMW of
N. Am., Inc., 501 F.3d 1274, 1281 (Fed. Cir. 2007); AK Steel Corp. v. Sollac & Ugine,
344 F.3d 1234, 1238–39 (Fed. Cir. 2003). The district court’s determination of the
hypothetical person of ordinary skill in the relevant art is a finding of fact we review for
2009-1350 8
clear error. Graham v. John Deere Co. of Kan. City, 383 U.S. 1, 17 (1966); Hybritech
Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379–80 (Fed. Cir. 1986).
Enablement is not precluded where a “reasonable” amount of routine
experimentation is required to practice a claimed invention, however, such
experimentation must not be “undue.” Enzo Biochem, 188 F.3d at 1371; Wands, 858
F.2d at 736–37. In Wands, we set forth the following factors that a court may consider
when determining if a disclosure requires undue experimentation:
(1) the quantity of experimentation necessary, (2) the amount of direction
or guidance presented, (3) the presence or absence of working examples,
(4) the nature of the invention, (5) the state of the prior art, (6) the relative
skill of those in the art, (7) the predictability or unpredictability of the art,
and (8) the breadth of the claims.
858 F.2d at 737. We explained that “[w]hether undue experimentation is needed is not
a single, simple factual determination, but rather is a conclusion reached by weighing
many factual considerations.” Id. The district court found that seven of the eight Wands
factors weighed in favor of a finding that undue experimentation would be required to
enable the full scope of the claims. ALZA fails to demonstrate that the court’s factual
findings in this regard are clearly erroneous. We conclude that they are not.
We agree first with the district court that the specification of the ’373 patent only
describes osmotic dosage forms and does not provide sufficient guidance for a person
of ordinary skill in the art to make the non-osmotic dosage forms as claimed. To the
extent that ALZA argues that the knowledge of a person of ordinary skill in the art
satisfies the enablement requirement, we disagree. As this court has repeatedly stated,
“the rule that a specification need not disclose what is well known in the art is ‘merely a
rule of supplementation, not a substitute for a basic enabling disclosure.’” Auto. Tech.,
2009-1350 9
501 F.3d at 1282 (quoting Genentech, 108 F.3d at 1366). To satisfy the plain language
of § 112, ¶ 1, ALZA was required to provide an adequate enabling disclosure in the
specification; it cannot simply rely on the knowledge of a person of ordinary skill to
serve as a substitute for the missing information in the specification.
In arguing that the disclosure in the ’373 patent specification does enable a
person of ordinary skill to make and use the claimed dosage forms, ALZA directs us to
ten lines of the specification, which mention non-osmotics and refer to a textbook
discussing how to make and use various types of non-osmotic sustained-release
dosage forms. See ’373 patent col.3 ll.53–62. The specification states:
There are many approaches to achieving sustained release of drugs from
oral dosage forms known in the art. These different approaches include,
for example, diffusion systems such as reservoir devices and matrix
devices, dissolution systems (including, for example, “tiny time pills”) and
matrix dissolution systems, combination diffusion/dissolution systems,
osmotic systems and ion-exchange resin systems as described in
Remington’s Pharmaceutical Sciences, 1990 ed., pp. 1682-1685.
Id. We agree with the district court that this disclosure provides “no guidance as to how
to achieve ascending release with non-osmotic oral dosage forms.” Alza, 607 F. Supp.
2d at 655. The “omission of minor details does not cause a specification to fail to meet
the enablement requirement. However, when there is no disclosure of any specific
starting material or of any of the condition under which a process can be carried out,
undue experimentation is required.” Auto. Tech., 501 F.3d at 1283–84 (quoting
Genentech, 108 F.3d at 1366).
The specification here does not contain “such full, clear, concise, and exact
terms as to enable any person skilled in the art” to make and use non-osmotic oral
dosage forms with ascending release rates. 35 U.S.C. § 112, ¶ 1. Instead, it provides
2009-1350 10
“only a starting point, a direction for further research.” Auto. Tech., 501 F.3d at 1284;
Genentech, 108 F.3d at 1366. Indeed, even ALZA concedes that a person of ordinary
skill in the art would have been required to engage in an iterative, trial-and-error process
to practice the claimed invention even with the help of the ’373 patent specification.
Thus, we agree with the district court that resolving the enablement issue in this case
rests on the underlying factual findings regarding whether undue experimentation is
required to make non-osmotic oral dosage forms with ascending release rates.
Despite ALZA’s assertions, we find no clear error in the district court’s finding that
the field of ascending release dosage forms was not mature at the time the ’373 patent
was filed and was a “breakaway” from the prior art, and thus, the preparation of such
dosage forms was not routine. Alza, 607 F. Supp. 2d at 652. These findings are
supported by the ’373 patent specification and prosecution history, and bolstered by
witness testimony.
In its challenge to the district court’s findings, ALZA relies heavily on the
testimony of its expert witness Dr. Martyn Davies, who explained that the
experimentation required here is merely routine. The district court gave little weight to
Dr. Davies’s testimony in this regard in light of contradictory testimony from other
witnesses. There is at least one problem with Dr. Davies’s testimony, and that is that
the level of skill in the art upon which he based his analysis is a higher level of skill than
the one the court adopted. 7 Dr. Davies did not contend that the specification would
7
While ALZA also challenges the district court’s determination of the level
of skill in the art on appeal, we find no clear error.
2009-1350 11
enable a person at the level of skill that the court adopted. Accordingly, we conclude
that the court did not clearly err in giving less weight to this testimony.
ALZA also challenges the district court’s reliance on the testimony of two of
ALZA’s own employees, Andrew Lam and Lawrence Hamel, who explained that despite
its efforts, ALZA had been unable to develop these purported “routine” non-osmotic
dosage forms exhibiting ascending release rates and that even development of the
osmotic form had been difficult. Specifically, ALZA argues that the district court’s
reliance on Lam’s testimony was misplaced because he is not skilled in the art and at
best testified that “trial-and-error” experimentation is required. ALZA also argues that
reliance on Hamel’s testimony was improper because it is irrelevant since it related only
to the difficulties in developing the osmotic form. We disagree because Lam’s and
Hamel’s level of skill in the art does not affect their knowledge relating to ALZA’s
difficulties in creating a non-osmotic dosage form as claimed, which was relevant to
ALZA’s arguments that the quantity of experimentation required was not undue. At trial,
ALZA argued that it did produce non-osmotic dosage forms with ascending release
profiles, offering the testimony of its scientist Atul Ayer for support. When Ayer could
not corroborate his statements, however, the district court found that Ayer’s testimony
actually cut against ALZA’s assertions that the preparation of such dosage forms was a
routine matter. Although ALZA complains that this consideration improperly shifted
Andrx’s burden on it, we disagree. This evidence merely contradicts its own witnesses’
2009-1350 12
testimony that such development was routine, easily made by those skilled in the art,
and created by ALZA. 8
We find no clear error in the district court crediting the testimony of Lam over Dr.
Davies and Ayer, and concluding that “ALZA had in fact tried and failed for a few
months to produce non-osmotic ascending release dosage forms.” Alza, 607 F. Supp.
2d at 653. The district court addressed the arguments that ALZA continues to make on
appeal in making credibility determinations and factual findings that ALZA was unable to
create non-osmotic dosage form with an ascending release rate and without undue
experimentation. We conclude that the district court did not clearly err in giving weight
to this testimony when finding that the quantity of experimentation required to practice
the claimed invention was undue based on the record as a whole.
Accordingly, ALZA has failed to demonstrate that the district court clearly erred in
the underlying factual findings on which the Wands factors are based. Rather, the
Wands factors weigh in favor of finding that the experimentation required to practice
part of the claimed invention was not routine. “Patent protection is granted in return for
an enabling disclosure of an invention, not for vague intimations of general ideas that
may or may not be workable.” Genentech, 108 F.3d at 1366 (citing Brenner v. Manson,
8
ALZA complains that the district court’s reliance on the “conclusory”
testimony of Andrx’s expert, Dr. Thomas Needham, further confirms that the court
improperly reversed the burden of proof. We find that the district court did not clearly
err in crediting the testimony of Dr. Needham, whose analysis was based on the level of
skill in the art that the court adopted. Dr. Needham stated that based on the lack of
guidance in the specification, a person of skill would need to engage in a great deal of
experimentation (six months or more) to develop a single, non-osmotic dosage form.
J.A. 12719. Dr. Needham also testified that based on the disclosure in the specification,
creating osmotic dosage forms would require one month of testing. Id. ALZA fails to
show that the court improperly shifted the burden of proof to ALZA or clearly erred in
relying on this testimony when weighing the Wands factors.
2009-1350 13
383 U.S. 519, 536 (1966)). Here, the evidence dictates that a person of ordinary skill in
the art would have been required to engage in undue experimentation to develop non-
osmotic oral dosage forms with ascending release rates.
As we stated in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371 (Fed. Cir.
2007), and repeated in Automobile Technologies, “The irony of this situation is that
Liebel successfully pressed to have its claims include a jacketless system, but, having
won that battle, it then had to show that such a claim was fully enabled, a challenge it
could not meet.” Auto. Tech. 501 F.3d at 1285 (quoting Liebel-Flarsheim, 481 F.3d at
1380). In this case, ALZA successfully argued to the district court that the claims
encompassed both osmotic and non-osmotic dosage forms. However, ALZA’s patent
specification does not enable the full scope of the claims, namely non-osmotic oral
dosage forms with ascending release rates. Rather, the clear and convincing evidence
based on the quantity of experimentation, lack of guidance in the specification, absence
of working embodiments, and breadth of the claims demonstrates that the ’373 patent
specification fails to enable a person of ordinary skill to make and use non-osmotic oral
dosage forms with ascending release rates. Therefore, the asserted claims fail to meet
the enablement requirement. See Auto. Tech., 501 F.3d at 1285.
We conclude that the asserted claims are invalid for lack of enablement under 35
U.S.C. § 112, ¶ 1. We need not address ALZA’s argument that the court erred in its
claim construction with respect to whether the claims require that the dosage form
administered in the claimed treatment release some drug during the first periodic
interval and thus in its finding of noninfringement, because the claims would be invalid
2009-1350 14
under any reasonable construction. Further, we need not reach Andrx’s argument that
in the alternative the claims are invalid as obvious under 35 U.S.C. § 103.
CONCLUSION
For the reasons set forth above, we affirm the district court’s determination that
the asserted claims are invalid for lack of enablement.
AFFIRMED
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