This document summarizes different types of pharmaceutical patent claims and infringement, including compound claims, composition claims, method of treatment claims, and process claims. It discusses strategies for challenging different claim types, such as challenging compound claims under 112 lack of enablement. It also provides examples of pharmaceutical patent litigation, including cases involving Protonix, Yasmin, Pepcid Complete, and Strattera where claims were found invalid due to obviousness or lack of enablement.

1. Litigating Infringement of Different
Types of Pharmaceutical Claims
Workshop on litigation strategies in
Pharmaceutical Patents by Linda Liu &
Partners , Beijing China.
18- 20 May, 2012.
Pravin Shejul, M.Sc., Ph.D. (LL.B.)

2. Types of Claims
• Compound
• Composition
• Method of Treatment
• Process of Manufacture
• Method of [mediating a biological pathway]
• Kit claims

3. Types of Infringement
• Statutory § 271(e)(2)(a)
▫ Filing of an ANDA
• Direct § 271(a)
▫ Make, use, sell, offer to sell, import
• Inducement § 271(b)
▫ Aid and abet direct infringement, requiring
 Knowledge
 intent
• Contributory § 271(c)
▫ offer to sell, sell, or import a material component of a patented
machine, manufacture, combination, or composition
 knowing the same to be especially made for use in an infringement of
such patent, and
 not a staple article of commerce
 Having no substantial noninfringing use

4. Types of Infringers
API manufacturers
Finished drug product
manufacturers
importers
wholesalers
Pharmacies
Doctors
Patients

5. Compound Claims
• A compound of Formula I, wherein . . .
• Typically the broadest of the claims, but usually
▫ the earliest filed
▫ the earliest to expire
▫ the subject of PTE
▫ the most difficult to invalidate or avoid
▫ the basis of a product LCM strategy

6. Compound Claims
• Frequent challenges under 102, 103, 112
• Although 2006 KSR case relaxed standards for
obviousness, still difficult to invalidate
compound claims as obvious
• BUT – challenging compound claims under
Section 112 increasingly successful

7. Structural Obviousness of Compound
Claims post-KSR
Consider the following case studies:
• Aciphex® (rabeprazole sodium)
• Actos® (pioglitazone)
• Protonix® (pantoprazole)
• Famvir® (famciclovir)

8. Aciphex® (rabeprazole sodium)
• Patented compound
is rabeprazole
sodium, a proton
pump inhibitor that
suppresses gastric
acid production by
inhibiting action of
the enzyme
H[+]K[+]ATPase

9. Aciphex® (rabeprazole sodium)
• Teva selected lansoprazole as the lead compound
for an obviousness-based invalidity argument
• Lower court rejected lansoprazole as lead
compound even though it was structurally the
closest
Eisai v. Dr. Reddy’s Lab’s, Inc.,
2008 U.S. App.LEXIS 15399 (Fed. Cir. July 21, 2008)

10. Aciphex® (rabeprazole sodium)
• Lansoprazole is an ulcer-treating compound
• Because of the differences between anti-ulcer
activity and gastric acid inhibiting activity, the
closest structural compound was not the
starting point for an obviousness analysis

11. Actos® (pioglitazone)
N O
NH
S
O
O
C2H5
N O
NH
S
O
O
H3C
• thiazolidinedione used
for treating diabetes
Closest prior art contained a methyl
group at an adjacent ring position
Actos®
Compound b

12. Actos® (pioglitazone)
• No motivation to start with compound b even
though an adjacent homologue
• Two other prior art references taught away from
the use of compound b
Takeda v. Alphapharm, et al.,
492 F.3d 1350 (Fed. Cir. 2007)

13. Protonix® (pantoprazole)
N
H
NOF
F
S
O
N
O O
N
H
NOF
F
S
O
N
O CH3
• Pantoprazole is a proton pump inhibitor:
• Teva alleged the claimed pantoprazole would have been obvious
based on the prior art disclosure of Compound 12 in USP 4,555,518:

14. Protonix® (pantoprazole)
• At-risk launch, Altana seeks PI
• District Court, following KSR, finds no likelihood of
success, denies PI motion
• Compound 12 was a natural choice for a lead compound
• Other prior art references taught:
▫ The desirability of lowering the pKa of the pyridine ring to a pKa
of 4 (the Sachs reference)
▫ a compound with a methoxy group at the 3-position of the
pyridine ring would have a lower pKa value (namely, a pKa of 4)
that a compound with a methyl group at that position (the Bryson
reference)

15. Protonix® (pantoprazole)
• KSR applied
• Defendants have provided “sufficiently
persuasive evidence that pantoprazole was a
predictable variation of compound 12 and thus,
is evidence of obviousness, at this stage of the
litigation. See KSR, 127 S. Ct. at 1740 ("If a
person of ordinary skill in the art can implement
a predictable variation, and would see the
benefit of doing so, section 103 likely bars its
patentability.").

16. Famvir® (famciclovir )
N
N
N
NH2N
OCOCH3
OCOCH3
Famciclovir
• Novartis sought a preliminary injunction against Teva’s at-risk
launch of famciclovir
• Famciclovir is a prodrug of penciclovir, an in-vivo active
compound with anti-viral activity

17. Famvir® (famciclovir )
• Applying KSR and Takeda (Actos), court
determined that penciclovir would have been an
obvious lead compound
• the 6-deoxy modification was shown in the prior
art to be several times more effective than any
other substitutions, therefore “skilled artisan
[would] have a reasonable expectation of success
based on the prior art.” citing KSR
Novartis v. Teva (D.N.J. Sept. 6, 2007)

18. Nexium® (magnesium esomeprazole
trihydrate)
• '504 Patent claims alkaline salts of
esomeprazole. Salt scope is in question.
• Patent describes and exemplifies only six salts
characterized throughout the specification as
"the invention"
• No description or enablement of other salts.
What other salts are legitimately covered?
• broad alkaline salt scope construction → 112
challenges

19. • Claims are facially generic to hydrated forms of esomeprazole
salts. No claim recitation of hydrate forms, no express
disclosure in the specification
• No disclosure for making a hydrated form
• Examples to not result in production of hydrated or even solvated form
• Later patents obtained on trihydrate form with characterization that
hydrated form could not have earlier been made
Yet claims purportedly cover specific hydrate forms
• Challenges under 112, lack of enablement and written
description
Plant Genetic Systems v. DeKalb Genetic Corp, 315 F.3d. 1335 (Fed.
Cir. 2003) (claims to transformed plant cell invalid, enabling for
monocots not accused dicots); compare In re Hogan (cannot use later
existing technology to invalidate patent that is enabled for what it
claimed at the time of filing)
Nexium® (magnesium esomeprazole trihydrate)

20. Composition Claims
• A pharmaceutical composition comprising
▫ a compound of formula X or a pharmaceutically
acceptable salt thereof
▫ An HPMC polymer matrix, and
▫ A pharmaceutically carrier

21. Biaxin®
• Pharmaceutical composition for extended
release of erythromycin comprising
erythromycin and from about 5-50% of
hydrophilic water-soluble pharmaceutically
acceptable polymer
• Combination of references showing:
1. controlled release formulation of azithromycin
with most preferred HPMC polymer
2. controlled release formulation of clarithromycin
with water soluble alginate salt release agent

22. Biaxin®
• second reference also disclosed:
▫ particular pharmacokinetic release
characteristics of composition that meet the
involved claims, and
▫ composition containing azithromycin

23. Biaxin®
Held:
• Clarithromycin is sufficiently similar to
azithromycin to provide a reasonable
expectation of success in substituting
clarithromycin for azithromycin in a controlled
release formulation
• Obvious to administer any macrolide antibiotic
in sustained release matrix to reduce adverse
gastrointestinal effects
Abbott Labs. v. Andrx Pharms., Inc.,
452 F.3d 1331 (Fed. Cir. 2006)

24. Ditropan XL®
• Sustained release oxybutynin obvious over
reference disclosing sustained release
composition for API highly soluble in water,
including oxybutynin, disclosing release of
morphine at claimed rates, where reference
provided motivation to use oxybutynin
Alza Corp. v. Mylan Labs., Inc.,
464 F.3d 1286 (Fed. Cir. 2006)

25. Combination of drug withCombination of drug with
drug coatingdrug coating
• Patents directed to APIs with drug coatings that
impart certain properties to the drug product
▫ Yasmin®
▫ Pepcid® Complete (a combination of famotidine
and aluminum hydroxide)

26. Yasmin® (oral contraceptive)
• combination of drospirenone and
ethinylestradiol
• drospirenone is acid sensitive and degrades in
patient’s stomach
• Bayer micronizes the combination and markets
Yasmin® as an
immediate release tablet

27. Yasmin® - post KSR analysis
• The prior art taught
▫ 2-4 mg drospirenone;
▫ in combination with 0.01 to 0.05 mg 17 [alpha]-
ethinylestradiol;
▫ along with pharmaceutically acceptable carriers;
▫ used as an effective oral contraceptive in human
females

28. Yasmin® - post KSR analysis
• Issue was whether it was obvious to a person of
ordinary skill in the art to:
(1) micronize drospirenone so as to increase its
bioavailability, and
(2) not protect the drospirenone from the
gastric environment with an enteric coating

29. Yasmin® - post KSR analysis
Held: ‘531 patent invalid as obvious
• micronization was a conventional formulation
technique to increase absorption and
bioavailability at the time of invention
• certain prior art references showed that a closely
related drug, spirorenone, absorbed rather than
isomerized
• other prior art references which note that poorly
water soluble sex steroids benefit from
micronization
Bayer Schering Pharma AG v. Barr Labs., Inc.,
(D.N.J . March 3, 2008)

30. Pepcid® Complete
• Patent covers a solid oral dosage of aluminum
hydroxide or magnesium hydroxide (the
"antacids") and famotidine
• Famotidine is a bitter-tasting guanidinothiazole
compound that inhibits acid secretion in the
stomach by interfering with histamine receptors
in the stomach lining
• The famotidine is separated from the antacids by
an impermeable coating because the antacids
would degrade the famotidine

31. Pepcid® Complete
• The prior art showed the combination of
uncoated famotidine and magnesium or
aluminum hydroxide in a solid oral dosage
• The Wolfe reference provided that compositions
combining antacids and H[2] blockers may
contain "one or more agents such as, for
example, sweetening agents, flavoring agents,
coloring agents and the like, in order to provide
a pharmaceutically elegant and palatable
preparation."
• The prior art ‘114 patent describes taste-mask
coating of drugs used in chewable tablets.

32. Pepcid® Complete
Held: ‘340 patent obvious in view of a
combination of references
• the combination of famotidine and antacids and
the use of an impermeable coating all appear in
the prior art
• Internal evidence shows McNeil
knew of famotidine’s bitter taste
• Pepcid AC® also involved coated
famotidine in the form of a
chewable tablet

33. Pepcid® Complete
• a skilled formulator would be motivated to mask
the bitter taste of famotidine even with the
addition of antacids
• Because the desirability of taste-masking
famotidine was established, “a person of
ordinary skill would have ample reason to
combine Davis and Wolfe with the '114 patent. It
also would have been obvious to combine Davis
and Wolfe with the '933 application.”
McNeil v. Perrigo,
516 F. Supp. 2d 238 (Fed. Cir. 2007)

34. Pepcid® Complete
Secondary Considerations
▫ Commercial success, but no nexus to the claimed
invention
 Pepcid brand successfully marketed
 Expensive promotional campaign
 cannibalization of Pepcid AC
 Coverage by at least 3 patents
McNeil v. Perrigo,
516 F. Supp. 2d 238 (Fed. Cir. 2007)

35. Method Claims

36. Lack of Enablement: Strattera®
• Lilly’s ‘590 patent is directed to the use of
atomoxetine HCl in treating ADHD
• Independent Claim 1:
“A method of treating attention-
deficit/hyperactivity disorder comprising
administering to a patient in need of such
treatment an effective amount of tomoxetine”
Eli Lilly and Company, v. Actavis, et al.,
2010 U.S. Dist. LEXIS 83292 (D.N.J. August 12, 2010)

37. Lack of Enablement: Strattera®
• Court finds claims nonobvious
• Court finds no inequitable conduct
• Full scope of claims enabled
• What about utility requirement of enablement?

38. Lack of Enablement: Strattera®
The '590 patent discloses:
• how to diagnose ADHD the disease to be treated,
• how to use tomoxetine to treat ADHD
• the preferred route of administration
• the preferred dosage form, and the dosage range for
children and adults
• that tomoxetine requires only once-a-day administration
• that the effective dose range of tomoxetine for ADHD
• that the use of tomoxetine to treat ADHD is effective

39. Lack of Enablement: Strattera®
• The '590 patent does not disclose any data or
testing regarding the efficacy of atomoxetine to
treat ADHD
• Def’s argued that the patentee did not establish
that the claimed method of treating ADHD had
utility at the time of filing
• Because no test results were provided at the time
of filing, a POSA would not have recognized the
claimed utility based on the ‘590 specification

40. Lack of Enablement: Strattera®
• Lilly argued:
▫ POSA would understand from the patent that
atomoxetine could be used to treat ADHD
▫ In addition, Lilly obtained positive clinical data
during the pendency of the patent
▫ Post-filing date evidence can be used to establish
utility

41. Lack of Enablement: Strattera®
December 1, 1994December 1, 1994 IND submitted to FDAIND submitted to FDA
January 3, 1995January 3, 1995 FDA approves Lilly’s proposedFDA approves Lilly’s proposed
clinical investigationclinical investigation
January 11, 1995January 11, 1995 ‘‘590 patent filing date590 patent filing date
May, 1995May, 1995 Positive clinical results reportedPositive clinical results reported
to Lillyto Lilly
October, 1995October, 1995 Positive clinical results publishedPositive clinical results published
by Lillyby Lilly

42. Lack of Enablement: Strattera®
Would a POSA have recognized that the claimed
method had utility as of the filing date?
• Existence of effective ADHD drugs
• Safety profile of atomoxetine
• Initiation of clinical trials

43. Lack of Enablement: Strattera®
Court says:
• Post-filing test results cannot be used to establish utility
at an earlier filing date:
“the utility requirement prevents a party from patenting a
mere research proposal or an invention that is simply an
object of research. . . the enablement/utility case law
instructs that patent applicants must demonstrate utility
(as well as other enablement-related requirements) at the
time of filing the patent application.”
Eli Lilly and Company, v. Actavis, et al.,
2010 U.S. Dist. LEXIS 83292 (D.N.J. August 12, 2010)

44. Lack of Enablement: Strattera®
• Patent held non-enabled
• No test data
• POSA would not have recognized utility
“The fact that testing had begun does not convince
this Court otherwise, as "usefulness" in the context
of a clinical study--which could include achieving
the open-ended goal of gaining additional
knowledge to assist in further research--is not the
same as "utility" for the purposes of patentability.”
Eli Lilly and Company, v. Actavis, et al.,
2010 U.S. Dist. LEXIS 83292 (D.N.J. August 12, 2010)

45. Inherent anticipation: Nexium®
1. A method for treatment of gastric acid related
diseases by inhibition of gastric acid secretion
comprising:
administering to a mammal in need of treatment a
therapeutically effective amount of
a proton pump inhibitor… or a pharmaceutically
acceptable salt thereof,
so as to effect decreased interindividual variation
in plasma levels (AUC) during treatment of gastric
acid related diseases.

46. Recited proton pump inhibitor was patented years before
"so as to effect decreased interindividual variation in plasma levels (AUC)
during treatment of gastric acid related diseases." construed as
"a smaller addition to the amount of any of the hormones secreted in the
pyloricantral mucosa of the stomach that stimulate secretion of stomach
acid by the parietal cells as compared to the addition produced by
omeprazole.”
patentee says not a mere inherent result but there is no need to carry out
a comparison step  recitation of a result inherent in the the
administration of known compound
Mayo v. Prometheus (“While it takes ….administration … to trigger a
manifestation of this relation… the relationship itself exists in principle
apart form any human action… natural processes.”)
patent eligibility: Nexium®

47. Method Claims
• What about divided Infringement?
• Generic mfr. submits proposed label to FDA
• FDA includes package insert to pharmacies
• Physician writes Rx for patient
• Patient fills prescription at pharmacy of choice

48. Method Claims

49. Does a generic drug manufacturer
infringe method of treatment claims?
• NO under 271(a)
“Defendants do not diagnose patients and do not
administer drugs. Moreover, Lilly has made no
allegation that Defendants will employ physicians to
prescribe tomoxetine to treat patients with ADHD. . .
. Defendants will not infringe Plaintiff's patent. Even
if Defendants manufacture, market, and sell
tomoxetine products, they would not be "using"
tomoxetine to treat ADHD.”
Lilly v. Actavis,
2009 U.S. Dist. LEXIS 43003, (D.N.J. May 20, 2009)

50. Does a generic drug manufacturer
infringe method of treatment claims?
• NO under 271(b)
“there is no evidence in the record that Apotex has directly
practiced or will ever practice any of the methods claimed in
the neurodegenerative method patent, all of which are
directed to a method for treating neurodegenerative diseases
by administering gabapentin or another cyclic amino acid
compound to a mammal. . . That is hardly surprising --
pharmaceutical companies do not generally treat diseases;
rather, they sell drugs to wholesalers or pharmacists, who in
turn sell the drugs to patients possessing prescriptions from
physicians. Pharmaceutical companies also occasionally give
samples of drugs to doctors and hospitals. In none of these
cases, however, does the company itself treat the disease.”
Warner-Lambert Co. v. Apotex Corp.,
316 F. 3d 1348, 1363 (Fed. Cir. 2003)

51. Does a generic drug manufacturer
infringe method of treatment claims?
• YES
“Navinta's Labeling instructs clinicians to use the
ANDA Products in a manner that would practice the
method of claim 6, and therefore instructs physicians to
infringe claim 6. [ ] Navinta reasonably knows or
should know that practitioners will use its ANDA
Products to practice the method of claim 6 of the '086
Patent.”
Abraxis v. Navinta
(D.N.J. August 3, 2009)
• Statements in a package insert that encourage
infringing use of a drug product are alone sufficient to
establish intent to encourage direct infringement.
AstraZeneca LP v. Apotex, Inc.,
2009 U.S. Dist. LEXIS 43677 (D.N.J. May 22, 2009)

52. Kit Claims
• “A kit for treating respiratory diseases, the kit
comprising (a) a budesonide composition in a sealed
container, the composition containing 0.05 mg to 15 mg
budesonide and a solvent, and (b) a label indicating
administration by nebulization in a continuing regimen
at a frequency of not more than once per day.”
• Held: kit claims invalid because the claimed budesonide
composition and suspension were known in the prior art
and the recited label could not render a known product
patentable.
AstraZeneca LP v. Apotex, Inc.,
633 F.3d 1042 (Fed. Cir. 2010)

53. Thank You!