Eli Lilly and Companyv.Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center

Patent Trial and Appeal Board

Oct 22, 2015

10779069 (P.T.A.B. Oct. 22, 2015)

Trials@uspto.gov Paper No. 45
571.272.7822 Entered: October 22, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________________

ELI LILLY AND COMPANY.,
Petitioner,

v.

LOS ANGELES BIOMEDICAL RESEARCH INSTITUTE
AT HARBOR-UCLA MEDICAL CENTER,
Patent Owner.
____________________

Case IPR2014-00693
Patent 8,133,903 B2
___________________

Before LORA M. GREEN, FRANCISCO C. PRATS, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

FINAL WRITTEN DECISION
35 U.S.C. § 318(a) and 37 C.F.R. § 42.73

I. INTRODUCTION
A. Background
Petitioner, Eli Lilly and Company (“Eli Lilly” or “Petitioner”), filed a
Petition requesting inter partes review of claims 1–5 (“the challenged
claims”) of U.S. Patent No. 8,133,903 B2 (“the ’903 patent”). Paper 1
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(“Pet.”). Patent Owner, Los Angeles Biomedical Research Institute at
Harbor-UCLA Medical Center (“LA Biomed” or “Patent Owner”), filed a
Corrected Patent Owner Preliminary Response. Paper 12 (Prelim. Resp.).
We determined that the information presented in the Petition and the
Preliminary Response demonstrated that there was a reasonable likelihood
that Petitioner would prevail in challenging claims 1–5 as unpatentable
under 35 U.S.C. § 102. Pursuant to 35 U.S.C. § 314, the Board instituted
trial on October 23, 2014, as to the challenged claims of the ’903 patent.
Paper 14 (“Institution Decision” or “Dec. Inst.”).
Patent Owner filed a Response (Paper 21, “PO Resp.”), but did not
file a motion to amend. Petitioner subsequently filed a Reply. Paper 26
(“Reply”). An oral hearing was held on June 16, 2015. The transcript of the
hearing has been entered into the record. Paper 44. Patent Owner also filed
a Motion for Observation on certain cross-examination testimony of
Petitioner’s declarant, Irwin Goldstein, M.D. (Paper 33, “Goldstein Obs.”),
as well as a Motion to Exclude Evidence (Paper 30).
We have jurisdiction under 35 U.S.C. § 6(c). This Final Written
Decision is issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73.
Based on the record before us, we conclude that Petitioner has not
demonstrated by a preponderance of the evidence that claims 1–5 of the
’903 patent are anticipated.
B. Related Proceedings
According to the parties, the ’903 patent is involved in the following
copending case: Los Angeles Biomedical Research Institute v. Eli Lilly &
Co., No. 2:13-cv-08567-JAK-JCG (C.D. Cal.). Pet. 56; Paper 5.
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In addition, Eli Lilly filed, concurrently with the instant Petition, an
additional petition for inter partes review of claims 1–5 of U.S. Patent
No. 8,133,903 B2 on different grounds, IPR2014-00752. A final decision is
being entered in that case concurrently with the final decision in the instant
case.
C. The ’903 Patent (Ex. 1001)
The ’903 patent issued on March 13, 2011, with Nestor F. Gonzalez-
Cadavid and Jacob Rajfer as the listed co-inventors. Ex. 1001. The
’903 patent relates to methods of treating fibrotic conditions with
phosphodiesterase (PDE5) inhibitors (e.g. sildenafil). Id. at 1:20–27. The
PDE5 inhibitor is administered at a dosage up to 1.5 mg/kg/day, wherein the
maximum dosage is roughly equivalent to the dose ingested by men with an
on-demand single 100 mg tablet. Id. at 45:7–12. Fibrotic conditions
disclosed in the ’903 patent include Peyronie’s disease (“PD”), erectile
dysfunction (“ED”), and arteriosclerosis. Id. at 1:29–2:46. The ’903 patent
discloses that the “[l]ong-term administration of nitrergic agents, such as . . .
sildenafil . . . may be of use to reduce PD plaque size and collagen/fibroblast
ratio and may reverse or prevent the further development of the fibrosis
observed in PD, ED, arteriosclerosis and other fibrotic conditions.” Id. at
3:8–14.
D. Challenged Claim
Petitioner challenges claims 1–5 of the ’156 patent. Claim 1 is
representative, and is reproduced below.

1. A method comprising:
a) administering a cyclic guanosine 3′, 5′-monophosphate
(cGMP) type 5 phosphodiesterase (PDE 5) inhibitor according
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to a continuous long-term regimen to an individual with at least
one of a penile tunical fibrosis and corporal tissue fibrosis; and
b) arresting or regressing the at least one of the penile tissue
fibrosis and corporal tissue fibrosis, wherein the PDE-5
inhibitor is administered at a dosage up to 1.5 mg/kg/day for
not less than 45 days.

E. Instituted Challenge
Claims Basis Reference
1–5 § 102 Whitaker1

II. ANALYSIS
A. Claim Construction
In an inter partes review, claim terms in an unexpired patent are
interpreted according to their broadest reasonable construction in light of the
specification of the patent in which they appear. 37 C.F.R. § 42.100(b); In
re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1276–79 (Fed. Cir. 2015);
Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766
(Aug. 14, 2012). Claim terms also are given their ordinary and customary
meaning, as would be understood by one of ordinary skill in the art in the
context of the entire disclosure. In re Translogic Tech., Inc., 504 F.3d 1249,
1257 (Fed. Cir. 2007). “[A] claim construction analysis must begin and
remain centered on the claim language itself, for that is the language the
patentee has chosen to ‘particularly point[ ] out and distinctly claim[ ] the
subject matter which the patentee regards as his invention.’” Innova/Pure
1 Whitaker et al. (“Whitaker”), Pub. No. WO 01/80860 A2, published
Nov. 1, 2001 (Ex. 1086).
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Water, Inc. v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1116 (Fed.
Cir. 2004); see also Pitney Bowes, Inc. v. Hewlett–Packard Co., 182 F.3d
1298, 1305 (Fed. Cir. 1999) (“The starting point for any claim construction
must be the claims themselves.”). Only terms which are in controversy need
to be construed, and then only to the extent necessary to resolve the
controversy. Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803
(Fed. Cir. 1999).
1. “at a dosage up to 1.5 mg/kg/day for not less than 45 days”
Neither party has offered an express construction for this claim
limitation, but instead the parties address the claim limitation “a continuous
long-term regimen,” which we also addressed in the Decision on Institution.
See Pet. 14–15; PO Resp. 22–25; Reply 11–12; Dec. Inst. 8–10. The plain
language of that limitation of claim 1, however, requires that a dosage up to
1.5 mg/kg/day be administered for at least 45 days. Also, administering a
dosage up to 1.5 mg/kg/day for at least 45 days would, according to the
language of the claim, meet the limitation of a “continuous, long-term
regimen,” as recited by claim 1.
We need not construe any other claim terms for purposes of this
Decision.
B. Patentability
To prevail on its challenges to the patentability of claims, Petitioner
must prove unpatentability by a preponderance of the evidence. 35 U.S.C.
§ 316(e); 37 C.F.R. § 42.1(d).
1. Anticipation by Whitaker
Petitioner contends that Whitaker anticipates independent claim 1.
Pet. 41–53. Petitioner sets forth claim charts indicating where each element
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of the claim is allegedly taught by the reference (id. at 42–46), and relies,
initially, on the Declaration of Dr. Goldstein (Ex. 1002). Patent Owner
disagrees with Petitioner’s assertions (PO Resp. 37–59), and relies on the
Declaration of Trinity J. Bivalacqua, M.D. Ph.D. (Ex. 2023) as evidence that
Whitaker does not anticipate the challenged claims. Petitioner then relies on
an additional Declaration of Dr. Goldstein (Ex. 1121) in its Reply.
a. Whitaker (Ex. 1086)
Whitaker discloses methods of treating male erectile dysfunction
involving the chronic administration of a PDE5 inhibitor at a dose of 1
mg/day to 10 mg/day. Ex. 1086, 4:13–23. Whitaker defines chronic as
follows:
The term “chronic or chronically” refers to the regular
administration of the product in intervals unrelated to the onset
of sexual activity. To receive the full benefit of the present
invention, chronic administration generally refers to regular
administration for an extended period, preferably daily for three
or more days, and still more preferably daily as long as the
patient suffers from erectile dysfunction (in the absence of
therapy). The term “chronic” administration encompasses other
regimens in addition to daily dosing. For example, chronic
administration encompasses administration of a sustained
release formulation that provides sufficient PDE5 inhibiter on a
regular basis and unrelated to the onset of sexual activity.
Contrary to acute or on-demand administration, chronic
administration does not link the administration of the PDE5
inhibitor to the onset of sexual activity (e.g., one hour prior to
intercourse).
Id. at 7:10–29.
Whitaker’s Example 6 discloses the results of five clinical studies
assessing the efficacy of daily oral dosing of a PDE5 inhibitor in males with
erectile dysfunction. Id. at 34–37. According to Whitaker:
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One study was of eight weeks duration, and the other four
studies were of twelve weeks duration. The Study Drug was
administered “daily” to patients with male erectile dysfunction.
“Erectile dysfunction (ED)” is defined as the persistent inability
to attain and/or maintain an erection adequate to permit
satisfactory sexual performance.
Id. at 34:17–24. There were four subgroups in the study, with the first
subgroup taking the study drug less than 30% of the time during the study,
the second subgroup taking the study drug 30% to 50% of the time during
the study, the third subgroup taking the study drug 50% to 70% of the time
during the study, and the fourth subgroup taking the study drug greater than
70% of the time during the study. Id. at 34:25–31. Whitaker teaches that
the “Study Drug was administered in 5 mg and 10 mg doses, ‘daily’ and not
more than once every 24 hours.” Id. at 35:3–4. As taught by Whitaker, a
better response was obtained with an increased frequency of dose. Id. at
36:1–4.
b. Analysis
Claim 1 is drawn a method of administering a PDE5 inhibitor, at a
dosage up to 1.5 mg/kg/day for not less than 45 days.
As to the claim limitation that the PDE5 inhibitor is administered at
least once a day for 45 days, Petitioner relies on Example 6 of Whitaker.
Pet. 43–44. Specifically, Petitioner contends that the study reported in
Example 6 of Whitaker lasted twelve weeks. Id. at 47.
Patent Owner contends that the chronic administration of Whitaker is
not the same as the long-term regimen required by claim 1. PO Resp. 46.
According to Patent Owner, although the studies in Example 6 of Whitaker
“were ostensibly of eight or twelve weeks duration, Whitaker makes clear
that the unidentified PDE-5 inhibitor . . . was not administered to the
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subjects on each and every day.” Id. at 48. Patent Owner contends that
Whitaker in fact teaches that the “drug was administered as infrequently as
30% of the days and at most a little more than 70% of the days during the
studies’ duration, with no requirement that the days on which the drug was
administered be consecutive [days].” Id.
Petitioner responds that Whitaker teaches daily treatment, and in fact,
the title of the publication is “Daily treatment for erectile dysfunction using
a PDE5 inhibitor.” Reply 19. As for long-term treatment, Petitioner
contends:
While Example 6 shows that treatment for 8–12 weeks was
contemplated, Whitaker expressly teaches a much longer
treatment period (i.e., “daily as long as the patient suffers
from erectile dysfunction (in the absence of therapy)”).
Ex. 1086 at 7:17–19 (emphasis added). As both parties’ experts
agree, this duration would be at least months, if not longer. Ex.
1122 at 298:20–300:8; Ex. 1121 at ¶¶ 114–15, 119, 122. Thus,
the prescription that would be written based on Whitaker would
likewise be for long-term use, i.e., “as long as the patient
suffers from erectile dysfunction.” Ex. 1086 at 7:17–19; Ex.
1121 at ¶¶ 119, 122.
Id. at 21.
We agree with Patent Owner that Petitioner has not demonstrated that
Whitaker anticipates claim 1 by a preponderance of the evidence. To
anticipate, a prior art reference “must not only disclose all elements of the
claim within the four corners of the document, but must also disclose those
elements ‘arranged as in the claim.’” Net MoneyIN, Inc. v. VeriSign, Inc.,
545 F.3d 1359, 1369 (Fed. Cir. 2008) (quoting Connell v. Sears, Roebuck &
Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983)).
Petitioner does not rebut Patent Owner’s argument that Example 6 of
Whitaker, at most, teaches dosing about 70% of the days. Rather, Petitioner
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relies on the title of Whitaker, which explicitly recites “daily dosing,” along
with the argument that Whitaker teaches that the treatment should continue
as long as the patient suffers from erectile dysfunction, which would be
months, if not longer. We are not persuaded.
Whitaker, although noting that the PDE5 inhibitor may be
administered daily as long as the patient suffers from erectile dysfunction,
specifically refers to regular administration for an extended period as being
preferably daily for three or more days. Ex. 1086, 7:10–25. Whitaker also
discloses that administering for as few as three days may effectively treat
erectile dysfunction. Id. at 38:29–39:1. Although the ordinary artisan may
have understood that patients may suffer from erectile dysfunction for
months, if not longer, that, at best, is an obviousness argument. Thus, that
argument is not sufficient to demonstrate, by a preponderance of the
evidence, an inherent description of continuous administration for at least 45
days as required by claim 1, especially in view of Whitaker’s teaching that a
therapeutically effective extended period may be as short as three days.
Moreover, in Example 6, when Whitaker actually administers for an
extended period of time, at most, the study drug is taken daily approximately
70% of the time during the study. Id. at 34:25–31. Therefore, we determine
that Petitioner has not demonstrated by a preponderance of the evidence that
Whitaker anticipates claim 1.
2. Claims 2–5
Claims 2–5 are dependent on claim 1, and thus incorporate all of the
limitations of that claim. Thus, the challenge of claims 2–5 as anticipated by
Whitaker fails for the same reason as the anticipation challenge of claim 1
fails.
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3. Conclusion
After considering Petitioner’s and Patent Owner’s positions, as well as
their supporting evidence, we determine that Petitioner has not shown by a
preponderance of the evidence that claims 1–5 are anticipated by Whitaker.
C. Patent Owner’s Motion to Exclude Evidence (Paper 30)
Patent Owner seeks to exclude Petitioner’s Exhibits 1103, 1106–1107,
1115–1116, 1118–1121, 1124, 1127, 1128–1130, 1131, 1135–1137, 1139–
1140, 1142, 1144, and portions of Dr. Bivalacqua’s deposition testimony
(Ex. 1122). As we did not rely on any of those exhibits in this Decision,
Patent Owner’s Motion to Exclude is dismissed as moot.
D. Motion for Observation (Paper 33)
Patent Owner’s observations are directed to the cross-examination
testimony of Dr. Goldstein (Ex. 2108), who was cross-examined after
Petitioner filed its Reply. Paper 33. As previously discussed, we did not
rely on the Dr. Goldstein’s Reply Declaration in this decision. Therefore,
we need not consider Patent Owner’s observations directed to the cross-
examination testimony of Dr. Goldstein.
E. Objections to Demonstratives
Each of Petitioner (Paper 42) and Patent Owner (Paper 43) objected to
the other’s demonstratives. In view of those objections, we expunge the
demonstratives from the record. Thus, Petitioner’s demonstratives
(Paper 41) and Patent Owner’s demonstratives (Paper 40), are expunged.

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III. CONCLUSION
Petitioner has not shown by a preponderance of the evidence that
claims 1–5 are unpatentable under 35 U.S.C. § 102 as anticipated by
Whitaker.

IV. ORDER
Accordingly, it is hereby:
ORDERED that Petitioner has not shown by a preponderance of the
evidence that claims 1–5 of the ’903 patent are unpatentable;
FURTHER ORDERED that Petitioner’s Motion to Exclude is
dismissed as moot;
FURTHER ORDERED that Papers 40 and 41 are expunged; and
FURTHER ORDERED that, because this is a Final Written Decision,
parties to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

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PETITIONER:

Mark Feldstein
Mark.feldstein@finnegan.com

Charles Lipsey
Charles.lipsey@finnegan.com

Michael Stramiello
Michael.stramiello@finnegan.com

Mark Stewart
Stewart_mark@lily.com

Dan Wood
Wood_dan@lily.com

PATENT OWNER:

David Tellekson
dtellekson@fenwick.com

Michael Shuster
mshuster@fenwick.com

Virginia DeMarchi
vdemarchi@fenwick.com

Ewa Davison
edavison@fenwick.com

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