UCB Biopharma Sprl

Patent Trials and Appeals Board

Jun 9, 2020

IPR2019-00400 (P.T.A.B. Jun. 9, 2020)

Trials@uspto.gov Paper No. 57
571-272-7822 Date: June 9, 2020

UNITED STATES PATENT AND TRADEMARK OFFICE

____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

APOTEX INC.,
Petitioner,

v.

UCB BIOPHARMA SPRL,
Patent Owner.
____________

IPR2019-00400
Patent 8,633,194 B2
____________

Before ROBERT A. POLLOCK, RYAN H. FLAX, and
KRISTI L. R. SAWERT Administrative Patent Judges.

POLLOCK, Administrative Patent Judge.

Final Written Decision
Determining No Challenged Claims Unpatentable
35 U.S.C. § 318(a)
Denying Patent Owner’s Motion to Exclude Evidence
37 C.F.R. § 42.64
Denying Petitioner’s Corrected Motion to Exclude Evidence
37 C.F.R. § 42.64
Decisions on Motions to Seal
37 C.F.R. §§ 42.1 and 42.54

IPR2019-00400
Patent 8,633,194 B2

2
I. INTRODUCTION
This is a Final Written Decision in an inter partes review challenging
the patentability of claims 1–11 of U.S. Patent No. 8,633,194 B2 (“the ’194
patent,” Ex. 1001). We have jurisdiction under 35 U.S.C. § 6.
Petitioner has the burden of proving unpatentability of a claim by a
preponderance of the evidence. 35 U.S.C. § 316(e) (2018). Having reviewed
the arguments of the parties and the supporting evidence, we find that
Petitioner has not demonstrated by a preponderance of the evidence that
claims 1–11 are unpatentable. For the reasons set forth below, we also deny
the parties’ motions to exclude evidence and grant, in-part, the proffered
motions to seal.
Procedural History
Apotex Inc. (“Petitioner”) filed a corrected Petition for an inter partes
review of claims 1–11 of the ’194 patent. Paper 4 (“Pet.”). UCB Biopharma
Sprl (“Patent Owner” or “UCB”) timely filed a Preliminary Response. Paper
11 (“Prelim. Resp.”). The parties further submitted an authorized Reply and
Sur-Reply to the Preliminary Response. Paper 13; Paper 16. In view of the
then-available, preliminary record, we concluded that Petitioner satisfied the
burden, under 35 U.S.C. § 314(a), to show that there was a reasonable
likelihood that Petitioner would prevail with respect to at least one of the
challenged claims. Accordingly, on behalf of the Director (37 C.F.R.
§ 42.4(a) (2018)), and in accordance with SAS Inst. Inc. v. Iancu, 138 S. Ct.
1348, 1353 (2018) and the Office’s Guidance on the Impact of SAS on AIA
IPR2019-00400
Patent 8,633,194 B2

3
Trial Proceedings (Apr. 26, 2018),1 we instituted an inter partes review of
all the challenged claims, on all the asserted grounds. Paper 17 (“Inst.
Dec.”), 21.
After institution, Patent Owner filed a Response. Paper 22 (“PO
Resp.”). Petitioner filed a Reply. Paper 33 (“Reply”). Patent Owner filed a
Sur-reply. Paper 38 (“Sur-reply”).
Petitioner filed a Corrected Motion to Exclude Evidence directed to
Exhibits 2024, 2030, 2031, and 2034. Paper 43. Patent Owner opposed that
motion (Paper 48) and Petitioner filed a Reply (Paper 49). Patent Owner
filed a Motion to Exclude Exhibits 1031–1038, 1040, 1041, and 1044. Paper
44. Petitioner opposed that motion (Paper 47) and Patent Owner filed a
Reply (Paper 50). Also before us are three motions to seal pursuant to the
default protective order. Papers 18, 28, 35.
On April 22, 2020, the parties presented arguments at oral hearing, the
transcript of which is of record. Paper 56 (“Tr.”).
Real Parties-in-Interest
Petitioner identifies itself, Apotex Corp., Apotex Holdings Inc., and
Apotex Pharmaceuticals Holdings Inc. as real parties-in-interest. Pet. 3.
Patent Owner asserts that its real parties-in-interest are UCB Biopharma
Sprl, UCB, Inc., UCB Pharma S.A., UCB S.A., and UCB Manufacturing
Inc. Paper 7, 2; Ex. 2008 (public version).

1 https://www.uspto.gov/patents-application-process/patent-trial-and-appeal-
board/trials/guidance-impact-sas-aia-trial.
IPR2019-00400
Patent 8,633,194 B2

4
Related Proceedings
The ’194 patent is at issue in UCB, Inc. v. Apotex Inc., No. 0-18-cv-
60846 (S.D. Fla.). See Paper 7, 2; Paper 10, 2. On April 1, 2019, the district
court in this related litigation issued an Order staying that case pending our
review of the ’194 patent. Ex. 3001 (order granting Apotex, Inc.’s motion to
stay pending inter partes review and administratively closing the case); see
also Paper 43, 6 (noting that the concurrent district court case remains
stayed).
Patent Owner also notes the ’194 patent was previously at issue in
UCB, Inc. v. Apotex Inc., 1:18-cv-03404 (S.D.N.Y.), which was voluntarily
dismissed. Paper 7, 2.
Asserted Grounds of Unpatentability
Petitioner asserts two grounds of unpatentability (Pet. 7, 8):
Ground Claims Challenged 35 U.S.C. § Reference(s)/Basis
1 1–11 103(a)2 Handbook3, WO ’0944

2 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
(2011) (“AIA”), amended 35 U.S.C. §§ 102 and 103. Because the
challenged claims of the ‘194 patent have an effective filing date before the
effective date of the applicable AIA amendments, we refer to the pre-AIA
versions of 35 U.S.C. § 103 throughout this Decision.
3AMERICAN PHARMACEUTICAL ASSOCIATION, HANDBOOK OF
PHARMACEUTICAL EXCIPIENTS (Arthur H. Kibbe, Ph.D. ed., 3d ed. 2000).
Ex. 1006.
4 International Patent Application Publication No. WO 2004/050094,
published June 17, 2004. Ex. 1007.
IPR2019-00400
Patent 8,633,194 B2

5
Ground Claims Challenged 35 U.S.C. § Reference(s)/Basis
2 1–11 103(a) Handbook, EP ’203,5 US
’5586
In support of its patentability challenges, Petitioner relies on, inter
alia, the testimony of Dr. Paul A. Laskar, Ph.D. See Exs. 1002, 1050 (first
and second Declarations, respectively); Ex. 1003 (curriculum vitae); Exs.
2010 and 2037 deposition transcripts). In opposition to these challenges,
Patent Owner relies on, inter alia, the testimony of Dr. Sarfaraz K. Niazi,
Ph.D. See Ex. 2014 (Declaration); Ex. 2098 (curriculum vitae); Ex. 1043
(deposition transcript).
The ’194 Patent and Relevant Background
According to the ’194 patent’s specification, its “invention is based on
the unexpected recognition that a pharmaceutical composition comprising an
active substance belonging to the family of substituted benzhydryl
piperazines and a reduced amount of preservatives is stable during a long
period of time.” Ex. 1001, 1:60–64; see also id. at 1:64–65 (defining
stability as “the capacity to resist[] . . . microbial contamination”). Such
combinations can be administered orally, by spray inhalation, and nasal
installation and may be formulated as drops, nasal drops, eye drops, ear
drops, and oral preparations such as a syrup. Id. at 5:8–29.

5 European Patent Application Publication No. 0605203 A2, published July
6, 1994. Ex. 1004.
6 U.S. Patent No. 5,698,558, issued Dec. 16, 1997. Ex. 1015.
IPR2019-00400
Patent 8,633,194 B2

6
The Specification further states that “[p]referably, the active substance
is selected from the group of cetirizine, levocetirizine, and their
pharmaceutically acceptable salts.” Id. at 2:19–21. By way of background,
we understand that these compounds have antihistamine activity. Cetirizine,
the active ingredient in the commercially available allergy relief product
Zyrtec, is a racemic mixture of (R) and (S) enantiomers; the levorotary R-
enantiomer (as levocetirizine dihydrochloride) is the active ingredient in the
commercially available Xyzal and Xyzal Allergy 24HR products. See
Ex. 1001, 2:22–48; Ex. 1008, 1123;7 Ex. 1011; Ex. 2007; and Ex. 3003.
The Specification suggests that compositions including cetirizine or
levocetirizine can employ a wide variety of preservatives (see, e.g.,
Ex. 1001, 3:19–44), but “[b]est results have been obtained with a mixture of
methyl parahydroxybonzoate and propyl parahydroxybonzoate in a ratio of
9/1 expressed in weight” (id. at 3:45–48). And, whereas the Specification
asserts that 3 mg/ml of parahydroxybenzoate esters is “a normal
concentration to preserve aqueous solutions” (id. at 1:64–2:4), it highlights
embodiments in which
the pharmaceutical composition contains an amount of
p-hydroxybenzoate esters (methyl p-hydroxybenzoate/propyl
p-hydroxybenzoate in a ratio of 9/1 expressed in weight) selected
in the range of 0.0001 and 1.5 mg/ml of the composition.
Preferably, it contains an amount selected in the range of 0.01

7 Jean-Paul Tillement et al., Compared pharmacological characteristics in
humans of racemic cetirizine and levocetirizine, two histamine H1-receptor
antagonists, 66(7) BIOCHEM. PHARMACOL. 1123–26 (2003).
IPR2019-00400
Patent 8,633,194 B2

7
and 1.125 mg/ml. More preferably it contains an amount of
preservatives selected in the range of 0.1 and 1 mg/ml.
Id. at 3:49–56; see also id. at 9:38–11:7 (Example 4 including oral
levocetirizine solution having 9/1 ratio of methyl p-hydroxybenzoate/propyl
p-hydroxybenzoate which comprise 0.75 mg/ml of the composition).
With respect to terminology, we accept Dr. Laskar’s testimony that
the methyl parahydroxybenzoate and propyl parahydroxybenzoate recited in
the ’194 patent are also known as methylparaben and propylparaben,
respectively, and generically as “parabens.” See, e.g., Ex. 1002 ¶¶ 53, 54, 80
n.14 (citing Ex. 1006, 340, 450); see also, e.g., Ex. 1013, 536 (alternative
spelling as “methyl paraben” and “propyl paraben). Methyl- and
propylparaben are also referred to as MP and PP, respectively, in the
prosecution history. See. e.g., Ex. 1013, 536–37.
Challenged Claims
The ’194 patent includes 12 claims. Of these, Petitioner challenges
claims 1–11, of which only claim 1 (reproduced below with paragraphing
added) is independent:
1. A liquid pharmaceutical composition comprising
(i) levocetirizine or a pharmaceutically acceptable salt of
levocetirizine, and
(ii) a preservative mixture consisting essentially of a mixture
of methyl parahydroxybenzoate and propyl parahydroxy-
benzoate in a ratio of 9/1 expressed in weight, said mixture
being present in an amount of more than 0 and up to 0.75
mg/ml of the composition,
wherein said composition is substantially free of bacteria.
IPR2019-00400
Patent 8,633,194 B2

8
Ex. 1001, 13:6–13.
Among the dependent claims before us, claim 4 recites that “the
composition is in the form of oral solutions, nasal drops, eye drops or ear
drops”; claim 11 is limited to “an oral solution comprising 0.50 mg/ml
levocetirizine dihydrochloride, 0.675 mg/ml methyl p-hydroxybenzoate, and
0.075 mg/ml propyl p-hydroxybenzoate”; and claims 8–10 are cast as
methods of making the composition according to claim 1. Id. at 13:19–21,
14:5–22.
Relevant Prosecution History
During the prosecution leading to the issuance of the ’194 patent, the
Examiner rejected certain claims as obvious over the combination of
Dietrich, DeLongueville, Doron, Gilliland I, Gilliland II, and Routlege.
Ex. 1013, 454–463; Exs. 2001–2006 (references cited in full at Prelim.
Resp., i). In response, Applicants amended then-pending claim 1 to include
the “consisting essentially of” and “substantially free of bacteria”
limitations. See Ex. 1013, 492, 495 (emphasis added). With these additions,
claim 1 recited:
1. A liquid pharmaceutical composition comprising
(i) levocetirizine or a pharmaceutically acceptable salt of
levocetirizine, and
(ii) a preservative mixture consisting essentially of a mixture
of methyl parahydroxybenzoate and propyl
parahydroxybenzoate in a ratio of 9/1 expressed in weight, said
mixture being present in an amount of more than 0 and up to
1.125 mg/ml of the composition,
wherein said composition is substantially free of bacteria.
IPR2019-00400
Patent 8,633,194 B2

9
See id. at 492 (paragraphing and emphasis added). In conjunction with these
amendments, Applicants submitted a Declaration of named inventor
Domenico Fanara, asserting that “[t]the combined parabens in typical
pharmaceutical preparations is at least about 2 mg/ml, as shown by an
accepted pharmaceutical treatise (see, Remington, The Science and Practice
of Pharmacy, 21st ed., 2005, pp. 748–749, Ex. B, hereinafter ‘the Remington
treatise’).” Id. at 536, ¶ 7. Mr. Fanara testified, however, that “[i]n the course
of developing liquid pharmaceutical formulations of levocetirizine and its
salts, we were surprised to discover that levocetirizine itself can act as an
anti-microbial.” Id. at ¶ 8. Mr. Fanara also submitted evidence purporting to
show the antibacterial efficacy of levocetirizine solutions having 0.375
mg/ml or 0.750 mg/ml of parabens consisting of methylparaben (MP) and
propylparaben (PP) in a 9/1 ratio. See id. at 536–37, ¶¶ 10–11. Upon
distinguishing the specific teachings of DeLongueville, Doron, Gilliland I,
and Gilliland II, Mr. Fanara stated that the combination of those references
“does not teach or suggest that a pharmaceutical formulation could be
prepared that is maintained substantially free of bacteria and having the a
[sic] total of MP and PP of no greater than 1.125 mg/ml, and no other
preservative.” Id. at 537–39, ¶¶ 12–17.
A subsequent Interview Summary Record shows that the Examiner
was not persuaded by Applicants’ argument that Remington taught a
combined paraben concentration of at least about 2 mg/ml. Id. at 571.
Rather, the Examiner found that “Remington discloses that parabens are
common preservatives used in liquid pharmaceutical dosage forms and their
typical concentrations levels range from about 0.1% [1 mg/ml] and up.”
IPR2019-00400
Patent 8,633,194 B2

10
Based on this reading of Remington—and Gilliland II’s teaching that
methylparaben and propylparaben have synergistic effects in combination—
the Examiner determined that one of ordinary skill in the art at the time of
the invention “would expect that MP/PP [methylparaben and propylparaben]
in a dose of about 1 mg/ml and slightly below would be . . . antimicrobial in
view of the prior art,” but “would not expect that amounts of MP/PP much
less than 1 mg/ml would be effective.” Id.
The Examiner then indicated that claims reciting a combined paraben
concentration of 0.75 mg/ml would be patentable, as follows:
A review of the data provided in the Declaration demonstrate that
compositions containing [levocetirizine] and MP/PP with ratio
of 9/1 and total concentration of 0.675 mg/ml and 0.375 have
antimicrobial effects. This is deemed to be surprising and
unexpected. Examiner noted that one of ordinary skill in the art
would not expect to have antimicrobial effects at these
concentrations based on the art of record, however based on the
art of record the upper limit of MP/PP amount of 1 mg/ml in
claim 5 and 1.125 mg/mg in claim 1 would not be unexpected.
The upper limit of claim 15 of 0.75 mg/ml is also considered to
be unobvious in view of the prior art. Examiner suggests
incorporating the upper limit of claim 15 (i.e.[,] 0.75 mg/ml) as
the upper limit in claim 1 to make the instant claims allowable.
Id. In light of the above, claim 1 was amended to recite the combined
paraben concentration of 0.75 mg/ml, as issued. Id. at 590, 612.
II. ANALYSIS
Principles of Law
“In an [inter partes review], the petitioner has the burden from the
onset to show with particularity why the patent it challenges is
IPR2019-00400
Patent 8,633,194 B2

11
unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed.
Cir. 2016) (citing 35 U.S.C. § 312(a)(3) (requiring inter partes review
petitions to identify “with particularity . . . the evidence that supports the
grounds for the challenge to each claim”)). This burden of persuasion never
shifts to Patent Owner. See Dynamic Drinkware, LLC v. Nat’l Graphics,
Inc., 800 F.3d 1375, 1378 (Fed. Cir. 2015) (discussing the burden of proof in
inter partes review).
A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
between the subject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious at the time the
invention was made to a person having ordinary skill in the art to which that
subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
(2007). The question of obviousness is resolved based on underlying factual
determinations including: (1) the scope and content of the prior art; (2) any
differences between the claimed subject matter and the prior art; (3) the level
of ordinary skill in the art; and (4) objective evidence of nonobviousness, if
present. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
In analyzing the obviousness of a combination of prior art elements, it
can be important to identify a reason that would have prompted one of skill
in the art “to combine . . . known elements in the fashion claimed by the
patent at issue.” KSR, 550 U.S. at 418. A precise teaching directed to the
specific subject matter of a challenged claim is not necessary to establish
obviousness. Id. Rather, “any need or problem known in the field of
endeavor at the time of invention and addressed by the patent can provide a
reason for combining the elements in the manner claimed.” Id. at 420.
IPR2019-00400
Patent 8,633,194 B2

12
Accordingly, a party that petitions the Board for a determination of
unpatentability based on obviousness must show that “a skilled artisan
would have been motivated to combine the teachings of the prior art
references to achieve the claimed invention, and that the skilled artisan
would have had a reasonable expectation of success in doing so.” In re
Magnum Oil Tools Int’l, Ltd., 829 F.3d 1364, 1381 (Fed. Cir. 2016) (internal
quotation marks and citations omitted). Under the proper inquiry,
“obviousness cannot be avoided simply by a showing of some degree of
unpredictability in the art so long as there was a reasonable probability of
success.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007).
Evidence of unexpected results and other objective indicia of
nonobviousness “must always when present be considered,” and can serve as
an important check against hindsight bias. See Cyclobenzaprine
Hydrochloride Extended-Release Capsule Patent Litigation, 676 F.3d 1063
1075–76, 1079 (Fed. Cir. 2012) (quoting Stratoflex, Inc. v. Aeroquip
Corp.,713 F.2d 1530, 1538–39 (Fed. Cir.1983)). Unexpected results must be
shown to be unexpected compared with the closest prior art. Kao Corp. v.
Unilever U.S., Inc., 441 F.3d 963, 970 (Fed. Cir.2006). There is, however,
no requirement that the closest prior art be commercialized. See In re
Merchant, 575 F.2d 865, 869 (CCPA 1978).
In addition, unexpected properties, even if found, do not necessarily
control the obviousness conclusion. See, e.g., Pfizer, Inc. v. Apotex, Inc. 480
F.3d 1348, 1372 (Fed. Cir. 2007). For example, a “marked superiority” in an
expected property may be enough in some circumstances to demonstrate
patentability, whereas a “mere difference in degree” may be insufficient. In
IPR2019-00400
Patent 8,633,194 B2

13
re Papesch, 50 CCPA 1084, 315 F.2d 381, 392 (CCPA 1963); In re
Merck, 800 F.2d 1091, 1099 (Fed. Cir. 1986) (evidence that a new drug had
more potent sedative and anticholinergic effects than the prior art
insufficient to outweigh the evidence of obviousness).
We analyze the instituted grounds of unpatentability in accordance
with these principles.
Person of Ordinary Skill in the Art
In determining the level of skill in the art, we consider the type of
problems encountered in the art, the prior art solutions to those problems, the
rapidity with which innovations are made, the sophistication of the
technology, and the educational level of active workers in the field. Custom
Accessories, Inc. v. Jeffrey-Allan Indus. Inc., 807 F.2d 955, 962 (Fed. Cir.
1986); Orthopedic Equip. Co. v. U.S., 702 F.2d 1005, 1011 (Fed. Cir. 1983).
Petitioner contends that a person of ordinary skill in the art as of the
relevant date would have
(i) a Pharm. D. or Ph.D. in chemistry, biochemistry, pharmacy,
pharmaceutics, or in a related field, and at least two years of
relevant experience in developing and formulating aqueous
pharmaceutical formulations; (ii) a master’s degree in the same
fields and at least five years of the same relevant experience; or
(iii) a bachelor’s degree in the same fields and at least seven years
of the same relevant experience.
Pet. 6 (citing Ex. 1002, ¶ 32–33); see Reply 7–8. Patent Owner does not
dispute Petitioner’s proposed definition of the skilled artisan. See Prelim.
Resp. 2 n.1; PO Resp. 8–9; Ex. 2034 ¶ 21–23. And as Petitioner’s proposed
definition is consistent with the cited prior art and the Specification, we
IPR2019-00400
Patent 8,633,194 B2

14
adopt it here. See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir.
2001) (explaining that specific findings regarding ordinary skill level are not
required “where the prior art itself reflects an appropriate level and a need
for testimony is not shown” (quoting Litton Indus. Prods., Inc. v. Solid State
Sys. Corp., 755 F.2d 158, 163 (Fed. Cir. 1985))).
Claim Construction
We interpret the challenged claims “using the same claim construction
standard that would be used to construe the claim in a civil action under
35 U.S.C. [§] 282(b).” See 37 C.F.R. § 42.100(b) (2019). Under that
standard, we presume that a claim term carries its “ordinary and customary
meaning,” which “is the meaning that the term would have to a person of
ordinary skill in the art in question” at the time of the invention. In re
Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007) (quoting
Phillips v. AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005)). Any special
definition for a claim term must be set forth in the specification with
reasonable clarity, deliberateness, and precision. In re Paulsen, 30 F.3d
1475, 1480 (Fed. Cir. 1994). Limitations, however, may not be read from the
specification into the claims (In re Van Geuns, 988 F.2d 1181, 1184 (Fed.
Cir. 1993)), nor may the Board “construe claims during [an inter partes
review] so broadly that its constructions are unreasonable under general
claim construction principles” (Microsoft Corp. v. Proxyconn, Inc., 789 F.3d
1292, 1298 (Fed. Cir. 2015), overruled on other grounds by Aqua Products,
Inc. v. Matal, 872 F.3d 1290 (Fed. Cir. 2017)).
IPR2019-00400
Patent 8,633,194 B2

15
As noted by Petitioner, columns 2 and 3 of the ’194 patent’s
Specification provide express definitions for some terms. Pet. 6; see also
Ex. 1001, 2:22–3:48 (defining, e.g., cetirizine, levocetirizine,
pharmaceutically acceptable salts, and preservatives). The parties agree that
no terms require express construction. Pet. 6; Prelim. Resp. 2 n.1., PO Resp.
8.
In our Institution Decision, however, we construed the claim term
“substantially free of bacteria,” as “having, at most, a low, but clinically
acceptable, level of bacteria, which would have been its ordinary meaning to
the skilled artisan because the claimed composition is a pharmaceutical, but
the term ‘substantially’ leaves some flexibility from absolute sterility.” Inst.
Dec. 12. We also noted that “claim 1 does not recite any requirement for the
level of resistance to bacterial contamination provided by the invention, nor
require that the composition is at any point exposed to bacteria, merely that
it is ‘substantially free of bacteria.’” Id. at 17. Neither party disputes our
initial definition, or offers an alternative, and we apply it here for clarity. See
Pet. Reply 16; PO Resp. 8. And, although Patent Owner further proposes
that “whether a particular formulation meets this requirement would be
guided by antimicrobial effectiveness testing set for by the United States
and/or European Pharmacopoeia,” such further construction is not necessary
here. See PO Resp. 8 (citing Ex. 2034 ¶ 27; Ex. 2010 77:14–78).
No other terms require express construction. See Vivid Techs., Inc. v.
Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly those
terms need be construed that are in controversy and only to the extent
necessary to resolve the controversy.”); see also Nidec Motor Corp. v.
IPR2019-00400
Patent 8,633,194 B2

16
Zhongshan Broad Ocean Motor Co. Matal, 868 F.3d 1013, 1017 (Fed. Cir.
2017) (applying Vivid Techs. in the context of an inter partes review).
Obviousness in view of the Handbook and WO ’094 (Ground 1)
As Ground 1, Petitioner challenges claims 1–11 as obvious in view of
WO ’094 and the Handbook. Pet. 19–43; Reply 3–24. Petitioner’s challenge
includes a detailed claim chart mapping the teachings of these references to
each element of claim 1. Pet. 19–21. Patent Owner Opposes. PO Resp.
26–52; Sur-reply 2–21. We have reviewed the evidence of record including
the Petition and Petitioner’s expert declarations and Patent Owner’s
arguments and evidence, including its experts’ declarations. We begin our
analysis with an overview of the references asserted under Ground 1.
1. Overview of the Handbook (Exhibit 1006)
The Handbook teaches that methylparaben and propylparaben are
“widely used as . . . antimicrobial preservative[s] in cosmetics, food
products, and pharmaceutical formulations.” Ex 1006, 340, 450.8 According
to the Handbook, antimicrobial activity and solubility vary inversely with
increasing paraben chain length. Id. at 340, 341. “A mixture of parabens is
thus frequently used to provide effective preservation,” moreover, “[a]ctivity
may be improved by using a combination of parabens, since additive effects
occur.” Id. “Activity may also be enhanced, due to synergistic effects, by

8 Where possible, we refer to native page numbers published in the cited
documents.
IPR2019-00400
Patent 8,633,194 B2

17
using combinations of parabens with other antimicrobial preservatives such
as imidurea.” Id.9
The Handbook teaches that methylparaben and propylparaben “are
affirmed GRAS [(generally regarded as safe)] Direct Food Substances in the
US at levels up to 0.1% [1 mg/ml]”10 and “[i]ncluded in the FDA Inactive
Ingredients Guide (IM, IV, and SC injections, inhalations, ophthalmic
preparations, oral capsules, solutions, suspensions and tablets, otic, rectal,
topical, and vaginal preparations).” Id. at 342, 452. The Handbook teaches,
for example, that “[m]ethylparaben (0.18%) [1.8 mg/ml] together with
propylparaben (0.02%) [0.2 mg/ml] has been used for the preservation of

9 Despite Petitioner’s initial assertion (and the ’194 patent’s Applicants’
failure to dispute the Examiner’s finding) that combinations of parabens
have synergistic antibacterial effects, we do not read the Handbook as
teaching that combinations of parabens alone have such properties. See Pet.
17, 23, 26, 29, 51; Ex. 1002 ¶¶ 85, 94, 102, 146; Ex. 1013, 339–40; PO
Resp. (citing excerpts of Dr. Laskar’s deposition testimony); Tr. 68:8–10.
Moreover, for the reasons set forth at pages 18–19 of Patent Owner’s Sur-
reply, Petitioner has not established that it was known in the art that methyl-
and propylparaben have synergistic effects. In any event, given that
combinations of methyl- and propylparaben were well known in the prior
art, any potential synergism has little relevance to the patentability of the
asserted claims. See In re Huellmantel, 324 F.2d 998, 1003 (CCPA 1963)
(“[W]e attribute no magic status to synergism per se since it may be
expected or unexpected.”); Tr. 59:3–6.
10 Dr. Laskar explains, and we accept, that the percentages of methyl- and
propylparabens in a solution may be converted from w/v percent to
milligrams per ml by multiplying the % value by a factor of 10. Ex. 1002
¶¶ 71–73. Thus, for example, “0.015% w/v of methylparaben corresponds to
0.15 mg/ml.” Id. ¶ 72. Dr. Niazi applies similar calculations. Ex. 2034 ¶ 135.
Bracketed amounts reflect that conversion.
IPR2019-00400
Patent 8,633,194 B2

18
various parenteral pharmaceutical formulations,” thus disclosing 2 mg/ml
total parabens with a 9:1 ratio of methyl- to propylparaben. Id. at 340, 450
(same). The Handbook, however, notes:
Although parabens have also been used as preservatives in
injections and ophthalmic preparations[,] they are now generally
regarded as being unsuitable for these types of formulations due
to the irritant potential of the parabens. These experiences may
depend on immune responses to enzymatically formed
metabolites of the parabens in the skin.
Id. at 342.
Despite this caution, the Handbook discloses additional information
regarding concentrations of methylparaben and propylparaben suitable for
particular applications, including “IM, IV, SC injections” and “Ophthalmic
preparations.” Id. at 340, 450. With respect to methylparaben, the Handbook
provides a table indicating the use of 0.065–0.25 % [0.65–2.5 mg/ml],
0.015–0.2 % [0.15–2.0 mg/ml], 0.033 % [0.3 mg/ml], and 0.015–0.2 %
[0.15–2.0 mg/ml] for injectable, oral, nasal, and ophthalmic solutions,
respectively. Id. at 340. A similar table indicates the use of 0.005–0.2 %
[0.05–2.0 mg/ml], 0.01–0.2 % [0.1–2.0 mg/ml], 0.017 % [0.17 mg/ml], and
0.005–0.01 % [0.05–0.1 mg/ml] of propylparaben for injectable, oral, nasal,
and ophthalmic solutions, respectively. Id. at 450. For convenience, we
reproduce below a compilation of the data from these two tables in the
Handbook for which Dr. Niazi has converted the concentration percentages
into mg/ml:
IPR2019-00400
Patent 8,633,194 B2

19

PO Resp. 23–24 (citing Ex. 2034 ¶ 135). The above table is a compilation of
data from the Handbook for which Dr. Niazi has converted the concentration
percentages of methyl- and propylparaben into mg/ml.
2. Overview of WO ’094 (Exhibit 1007)
WO ’094 is directed to the use of levocetirizine for the treatment of
persistent allergic rhinitis, wherein: “[a] preferred daily dosage provides
from about 0.0005 mg to about 2 mg of levocetirizine or a pharmaceutically
acceptable salt thereof, per kg of body weight per patient . . . [and] may be
administered once per day of treatment, or divided into smaller dosages.”
Ex. 1007, Abstract, 1:10–27, 2:35–3:2.
WO ’094 further discloses that levocetirizine compositions may be
formulated as, for example, aerosols, solids, creams, and liquids, including
oral solutions such as syrups and drops. Id. at 4:8–29. Such dosage forms
“may be prepared according to conventional methods used by pharmacists,”
and include “substances conventionally used as preserving, stabilizing,
moisture-retaining, and emulsifying agents.” Id. at 3:16–26.
IPR2019-00400
Patent 8,633,194 B2

20
WO ’094 discloses that “[b]est results have been obtained with an oral
dosage form, in particular liquid formulations such as syrup for children, and
film-coated tablet for adults.” Id. at 4:24–25. In one preferred embodiment,
WO ’094 discloses a film coated tablet comprising “levocetirizine
dihydrochloride, magnesium stearate, cellulose, lactose and silicon dioxide.”
Id. at 4:31–32. In another preferred embodiment, WO ’094 discloses a syrup
formulation of “levocetirizine dihydrochloride, methyl- and propylparaben,
saccharinum, and purified water.” Id. at 4:33–35.
3. Analysis of Ground 1
For Ground 1, Petitioner argues that one of ordinary skill in the art
seeking to make a liquid pharmaceutical composition comprising
levocetirizine would have looked first to WO ’094, which discloses a
preferred oral syrup formulation of “levocetirizine dihydrochloride,
methyl- and propylparaben, saccharinum, and purified water.” Pet. 21;
Ex. 1007, 4:34–35; see section II(D)(2), above. Petitioner argues that
because WO ’094 is silent as to the ratio and amounts of methyl- and
propylparabens in the formulation, the skilled artisan would have looked to
the Handbook for guidance. Pet. 22–23.
a) “a mixture of methyl parahydroxybenzoate and propyl
parahydroxybenzoate in a ratio of 9/1 expressed in
weight”
With respect to the ratio of methyl- to propylparabens, Petitioner
points to the 9/1 ratio taught by the Handbook for non-oral (e.g., injectable)
formulations. Id. at 23 (quoting Ex. 1006) (“[m]ethylparaben (0.18%) [1.8
mg/ml] together with propylparaben (0.02%) [0.2 mg/ml] has been used for
IPR2019-00400
Patent 8,633,194 B2

21
the preservation of various parenteral pharmaceutical formulations”).
According to Petitioner’s expert, Dr. Laskar, the 9/1 ratio is not limited to
parenteral formulations, but is “widely used across a variety of dosage
forms . . . [and] would logically have commended itself to the attention of
the POSA as of the priority date of the ’194 patent.” Ex. 1002 ¶ 88
(referencing exemplary formulations employing the 9/1 ratio).
In response, Patent Owner asserts that one of ordinary skill in the art
seeking to make a liquid pharmaceutical composition of levocetirizine would
not have been motivated to apply the 9/1 ratio of methyl- and
propylparabens recited in the Handbook and in the additional examples
provided at paragraph 88 of Dr. Laskar’s first Declaration. PO Resp. 24–25.
With respect to the example in the Handbook, Patent Owner asserts that it
“does not identify the API for this formulation, nor does it state that the
formulation was effective or useful in any manner.” Id. at 22 (citing
Ex. 2034 ¶ 140). Patent Owner further argues that we should discount the
exemplary formulations cited by Dr. Laskar as non-analogous art because
they, for example, do not contain antihistamines, refer to gel or jelly
formulations, comprise additional preservatives, or lack evidence that they
have undergone regulatory testing. Id. at 24–25, 42–44 (citations omitted).
We do not find Patent Owner’s arguments on this issue persuasive for
the reasons set forth on pages 4 and 5 of Petitioner’s Reply. In short, there is
no dispute that the only ratio of methyl- to propylparaben exemplified in the
Handbook is 9/1, and that disclosure pertains to a liquid (parenteral)
IPR2019-00400
Patent 8,633,194 B2

22
formulation.11 And despite Patent Owner’s attempt to distinguish the
exemplary formulations cited by Dr. Laskar, those examples clearly support
his testimony that the 9/1 ratio of methylparaben to propylparaben “is
common and is widely used across a variety of dosage forms.” Ex. 1002
¶ 88; see Ex. 2010, 95:4–10, 124:8–14, 134:13–14. Patent Owner does not
persuade us to the contrary. But see Ex. 2034 ¶ 176 (Dr. Niazi’s testimony
that: “In my experience, a 9:1 ratio is not ‘widely used’ in pharmaceutical
formulations.”); Ex. 1004 (11:22–42 liquid ophthalmic formulation using
2/1 ratio of methyl- to propylparaben).
Further, and though not necessary to our determination, the
obviousness of the 9/1 ratio is further supported by documents and testimony
elucidated at Dr. Niazi’s deposition. As Petitioner points out, Dr. Niazi is the
sole author of the six volume Handbook of Pharmaceutical Manufacturing
Formulations (“Niazi series”) the first edition of which published prior to the
filing date of the ’194 patent. See Reply 5. Dr. Niazi did not dispute that
volumes 3 and 5 of his Niazi Series includes 33 formulations having a 9/1
ratio of methylparaben to propylparaben, including one for cetirizine
hydrochloride syrup. See id. at 5–6 (citing, e.g., Ex. 1031; Ex. 1043, 171:16–
172:14, 173:15–175:19). Accordingly, and considering all the evidence of
record, we find that one of ordinary skill in the art seeking to make a liquid

11 Notwithstanding Patent Owner’s statement that “a parenteral formulation
is fundamentally different than the formulations of the challenged claims,”
we find no support for the suggestion that the liquid pharmaceutical
composition of claim 1 excludes parenteral formulations. See PO Resp. 43
(citing Ex. 2034 ¶ 38; Ex. 2010, 36:12–37:8); Tr. 17:3–7.
IPR2019-00400
Patent 8,633,194 B2

23
pharmaceutical composition comprising levocetirizine would have found it
obvious to use a 9/1 ratio of methylparaben to propylparaben.
b) “in an amount of more than 0 and up to 0.75 mg/ml of
the composition”
With respect to the amount of methyl- and propylparabens, Petitioner
points to the Handbook’s teaching to use 0.015–0.2% [0.15–2.0 mg/ml]
methylparaben in oral solutions and suspensions. Pet. 27 (citing Ex. 1006,
340, Table 1). Based on this range of methylparaben, Dr. Laskar calculates
that a 9/1 ratio of methyl- to propylparaben equates to 0.017–0.22 mg/l of
propylparaben. Ex. 1002 ¶¶ 96–97 (cited at Pet. 27–28). Thus, starting with
the Handbook’s range for methylparaben in oral solutions and suspensions,
and applying a 9/1 ratio to the corresponding amount of propylparaben,
Dr. Laskar arrives at total paraben concentration of 0.167 mg/ml–2.22
mg/ml. Id. ¶ 98 (cited at Pet. 27–28). Based on this calculation, Dr. Laskar
concludes that because “the prior art ranges of the total amount of the p-
hydroxybenzoate esters (i.e., 0.167 mg/ml-2.22 mg/ml) overlap with the
recited ranges (i.e., > 0 to 0.75 mg/ml),” the range recited in claim 1 would
have been obvious to one of ordinary skill in the art. Id. ¶¶ 98–101 (cited at
Pet. 28–29).
Noting that the range calculated by Dr. Laskar includes total amounts
of parabens well above the claimed range, Petitioner further argues that one
of ordinary skill in the art would have been motivated to use the lower
amounts of parabens “within the workable ranges reported in the Handbook
for oral solutions and suspensions” to minimize their irritant potential and as
“common sense notion . . . to use as little of a particular compound as
IPR2019-00400
Patent 8,633,194 B2

24
possible to achieve the desired effect.” Pet. 29–30 (citing Ex. 1002 ¶¶ 102–
103). In sum, it is Petitioner’s position that “a POSA would have been
motivated to use no more paraben than needed, or lower the amounts of
parabens while still in the ranges disclosed in the Handbook.” Id at 29.
“Thus,” Petitioner asserts, “using the lower amount of “more than 0 and up
to 0.75 mg/ml” of total parabens while maintaining the 9/1 ratio would have
been obvious.” Id. at 29–30 (citing Ex. 1002 ¶ 103).
(1) Dr. Laskar’s Calculation
Patent Owner responds that the Petition’s Ground 1 is predicated on a
calculation that “take[s] the range of methylparaben for oral solutions and
suspensions listed in the Handbook (0.15-2 mg/mL) and multipl[ies] it by 9
(pursuant to the Handbook’s parenteral example) to determine the
appropriate amount of propylparaben (0.017-0.22 mg/mL).” PO Resp. 38
(citing Pet. 27–28, 51–52; Ex. 1002 ¶¶ 95–98, 140–143). Patent Owner
contends that this calculation only supports Petitioner’s argument if it uses
methylparaben as the starting point for the 9/1 calculation and does not
consider what happens if propylparaben is the starting point. Id. at 39.
Relying on the testimony of Dr. Niazi, Patent Owner reasonably asserts that
if propylparaben were instead used as the starting point for Petitioner’s
calculation, the range of total parabens would be 1–2 mg/ml, which falls
outside of the claims of the ’194 patent. Id. (citing Ex. 2034 ¶ 174); see
Ex. 2034 ¶ 179, n.4.
In our Institution Decision, we expressly suggested that the parties
“explore. . . why one of ordinary skill in the art would base the 9/1
calculation upon the Handbook’s range for methylparaben rather than for
IPR2019-00400
Patent 8,633,194 B2

25
propylparaben.” Inst. Dec. 16, n.3. Dr. Lasker declined to do so. Ex. 2010,
75:19–76:3; Ex. 1050. At best, when pressed at his deposition, Dr. Lasker
offered the opinion that
methylparaben is more water soluble than propylparaben, as one
can see from the information in the Handbook. And to, therefore,
base the calculation on the more water soluble of the two
parabens makes sense to me. The other is that on those occasions
when I have used a combination of methyl and propylparaben,
that’s -- the progress sequence that I used is I start with
methylparaben and then calculate the amount of propylparaben I
would end up using.
Ex. 2010, 76:4–15. Dr. Niazi, in contrast, testifies that if one of ordinary
skill in the art were to perform that calculation “they would start with
propylparaben because propylparaben is the more active antimicrobial and
the POSA would want to ensure that a minimum amount of propylparaben is
used.” Ex. 2034 ¶ 174. Weighing the available evidence, we find Dr. Niazi’s
explanation more credible. When using Dr. Niazi’s methodology, the
claimed paraben amounts are not taught or suggested by the cited prior art.
Moreover, even were we to give equal weight to the two possibilities,
Petitioner would not prevail as it bears the burden of proving unpatentability
by a preponderance of the evidence. Here, Dr. Lasker points to no specific
evidence that a POSA would have started with methylparaben, other than his
personal opinion that a POSA could have done so. See Belden Inc. v. Berk-
Tek LLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015) (“[O]bviousness concerns
whether a skilled artisan not only could have made but would have been
motivated to make the combinations or modifications of prior art to arrive at
the claimed invention.”). Dr. Lasker’s opinion on this matter does not
IPR2019-00400
Patent 8,633,194 B2

26
amount to a preponderance of the evidence and we find Dr. Niazi’s opinion
on the matter more credible.
(2) Motivation to Explore Low Paraben
Concentrations
Noting that the Handbook reports on the “irritant potential of
parabens,” Petitioner posits that one of ordinary skill in the art “would have
been motivated to lower the amounts of parabens within the workable ranges
reported in the Handbook for oral solutions and suspensions, because it
would have stood to reason that using less parabens would have resolved
any irritant issues, while maintaining the widely used 9/1 ratio.” Pet. 29
(citing Ex. 1006, 342; Ex. 1002, ¶¶ 102–103); see Reply 8–10. According to
Dr. Lasker, “[t]his represents nothing more than the common sense notion to
a POSA to use as little of a particular compound as possible to achieve the
desired effect.” Ex. 1002 ¶ 103.
As Dr. Niazi points out, however, every reference cited by Dr. Laskar
as exemplifying the use of parabens uses at least 2 mg/ml total parabens—
and, thus, well above the upper limit of 0.75 mg/ml recited in claim 1 .
Ex. 2034 ¶ 183 (citing Exs. 1017–1020); see Sur-reply 2. Moreover, both
parties’ experts testified that they could not identify any formulation using
less than 2 mg/ml total parabens, yet neither expert had experienced
irritation due to parabens. See PO Resp. 46; Ex. 2034 ¶¶ 181–184; Ex. 2010,
123:22–4, 124:15–19.
We also find supportive of Patent Owner’s position the evidence from
Dr. Niazi’s Handbook of Pharmaceutical Manufacturing presented by
Petitioner at Dr. Niazi’s deposition and summarized in Exhibit 1031. Sur-
IPR2019-00400
Patent 8,633,194 B2

27
reply 2–3 (citing Ex. 1013, 571, 587–588). Of the 33 formulations presented
in the Niazi series, 21 of them used 2 mg/ml total parabens, moreover, even
Entry No. 4 for Cetrizine Hydrochloride Syrup uses 1 mg/ml total parabens,
which as Patent Owner points out “is the amount the Examiner found
obvious during prosecution which caused applicants to lower the claimed
amount to 0.75 mg/mL or less.” Sur-reply 2–3 (citing Ex. 1013, 571, 587–
588).
One of the 33 Examples from the Niazi Series, Entry No. 33, Vitamin
B Complex and Iron Syrup, does recite a combined paraben concentration
within the claimed range. We, nevertheless, accord this entry somewhat less
weight in our analysis because, having been introduced at such a late stage
of the proceeding, the parties have had limited opportunity to explore the
underlying properties of Entry No. 33 such as, for example, whether the iron
component itself has antibacterial properties. We, nevertheless, credit
Dr. Niazi’s testimony that the USP designation for syrup means that it has
“66 percent weight by weight and 85 percent weight by volume of sugar, at
which point no bacteria can grow in it.” Ex. 1043, 208:17–209:16. Because
the challenged claims require “a preservative mixture consisting essentially
of a mixture of methyl parahydroxybenzoate and propyl parahydroxy-
benzoate,” the transitional phrase limits the scope of a claim to the specified
components “and those that do not materially affect the basic and novel
characteristic(s)” of the claimed invention. In re Herz, 537 F.2d 549, 551-52
(CCPA 1976) (emphasis in original); see Pet. 22, n.12; Sur-reply 20.
Accepting, on the limited record before us, Dr. Niazi’s testimony regarding
the definition and antibacterial properties of syrups, the Vitamin B Complex
IPR2019-00400
Patent 8,633,194 B2

28
and Iron Syrup example is outside the scope of the claimed invention
because the antimicrobial properties of such syrups would materially affect
the basic and novel characteristic of the invention, i.e., the maintenance of a
composition that is substantially free of bacteria using only the “preservative
mixture” recited. See Tr. 26:19–22. Accordingly, and, absent additional
evidence, the relevance of Entry No. 33 is unclear.
Accordingly, and rather than being motivated to use lower paraben
concentrations as Dr. Lasker contends, we find credible Dr. Niazi’s opinion
“that a POSA would have deferred to a formulation that includes parabens,
specifically in amounts within the ranges found in earlier pharmaceutical
formulations, instead of simply seeking to minimize parabens” and “any
purported irritant potential would not cause a POSA to eliminate or
substantially lessen the amount of parabens given the severe risks of
bacterial contamination.” Ex. 2034 ¶¶ 181–182. We further find credible
Dr. Niazi’s opinion that the risk-reward benefit of using lower amounts of
parabens did not justify such experimentation:
Parabens were inexpensive to obtain and use, and were known to
be safe and effective. See supra § VIII.C-D. Further, if a POSA
used a lower amount of parabens than what was known in the art
to be effective and later the formulation became contaminated,
the POSA could be exposed to liability for using a lower amount
of parabens. See supra § VIII. This is especially true when the
formulation may be administered to vulnerable patient
populations, such as young children. See supra § VIII.C.
Id. ¶ 185. Moreover, and despite the parties’ dispute regarding whether the
combination of methy- and propylparabens are synergistic, we further note
Dr. Niazi’s opinion that “the formulations in question involving mixtures of
IPR2019-00400
Patent 8,633,194 B2

29
parabens and the main advantage of mixing preservatives is that it allows a
higher concentration (not a lower concentration) of preservatives in the
formulation.” Id.; see also PO Resp. 20–22, 30–31; Reply 12–14; Sur-Reply
18–19; Ex. 2010, 70:1–71:10.
In sum, we find that Petitioner has not established that one of ordinary
skill in the art would have been motivated to use “more than 0 and up to 0.75
mg/ml” of total parabens in a liquid levocetirizine formulation as required by
independent claim 1.12, 13
(3) Conclusion as to Ground 1
For the above reasons Petitioner has not carried its burden to establish, by
a preponderance of the evidence, that the challenged claims are unpatentable
under Ground 1.

12 Given the limited development of evidence adduced at Dr. Niazi’s
deposition, we do not address whether the record as a whole supports Patent
Owner’s teaching away argument. See PO Resp. 44–46; Sur-reply 3–4.
13 We also give little weight to Patent Owner’s unexpected results arguments
for lack of comparison to the closest prior art, which would reasonably
include the any of the cetirizine hydrochloride formulations of EP ’203, or
the levocetirizine syrup formulation of WO ’094. See PO Resp. 47–49, 58;
Tr. 66:9–15 (Patent Owner’s counsel stating “there is no appropriate closest
prior art because it would not be expected that levocetirizine could have [an
intrinsic antibacterial] property”) see also Ex. 1016, 98 (identifying EP ’203,
inter alia, as closest prior art in related EPO opposition).
IPR2019-00400
Patent 8,633,194 B2

30
Obviousness in view of the Handbook, EP ’203, and US ’558
(Ground 2)
As Ground 2, Petitioner challenges the ’194 patent’s claims 1–11 as
obvious in light of the Handbook, EP ’203, and US ’558. Pet. 43–63; Reply
24–27. Petitioner’s challenge includes a detailed claim chart mapping the
teachings of these references to each element of claim 1. Id. at 45–46. Patent
Owner Opposes. PO Resp. 52–58; Sur-reply 2–21. As the teachings of the
Handbook are discussed in section II(D)(1), above, we begin our analysis
with an overview of EP ’203 and US ’558.
1. Overview of EP ’203 (Exhibit 1004)
EP ’203 is a European Patent Application titled “Antiallergic
composition for ophthalmic or nasal use” and directed to liquid formulations
of cetirizine that address stability and irritation problems associated with
high and low concentration formulations of cetirizine. Ex. 1004, 2:40–48;
Ex. 2034 ¶ 103. EP ’203 purports to solve this problem by using
cyclodextrin as an additive. Ex. 1004, 3:1–19; Ex. 2034 ¶ 104.
EP ’203 broadly discloses an “antiallergic composition for ophthalmic
or nasal use, comprising cetirizine or a salt thereof as an active ingredient.”
Ex. 1004, Abstract. The reference discloses that such compositions “may
further contain any conventional additives in suitable amounts, which are
used in ordinary ophthalmic or nasal solutions, e.g., preservatives such as p-
hydroxybenzoates . . . . The amount of additive to be used can be determined
by those skilled in the art within the same range as adopted for ordinary
ophthalmic or nasal solutions.” Ex. 1004, 3:52–57.
IPR2019-00400
Patent 8,633,194 B2

31
EP ’203 includes eight examples of cetirizine formulations, all of
which are either nasal or ophthalmic formulations. Id. at 9:44–13:18. Of
these, only Examples 5 and 7 contain preservatives. See Pet. 44 (citing
Ex. 1002 ¶ 131); Ex. 2034 ¶ 106.
Example 5 of EP ’203 discloses the following formulation for a
cetirizine ophthalmic solution:
Id. at 11:22–42. The table above sets forth amounts of cetirizine
hydrochloride, methylparaben, propylparaben, and other ingredients. As
noted by Patent Owner, “converting the units in EP ’203 Example 5 to those
used in the ’194 patent shows that Example 5 includes 2 mg/ml of
methylparaben and 1 mg/ml of propylparaben for a total of 3 mg/ml
combined parabens.” PO Resp. 19 (citing Ex. 2034 ¶ 110; Ex. 2010 132:7–
16, 138:25–139:3).
IPR2019-00400
Patent 8,633,194 B2

32
Example 7 of EP ’203 discloses the following formulation for a
cetirizine nasal solution:
Ex. 1004 12:22–49. The above-disclosed table sets forth amounts of
cetirizine hydrochloride, benzalkonium chloride, and other ingredients. As
noted in the Petition, EP ’203 identifies benzalkonium chloride as a
“conventional” preservative. Pet. 44 (citing Ex. 1004, 3:51–53).
2. Overview of the US ’558 (Exhibit 1015)
US ’558 teaches that cetirizine comprises a mixture of (+) and (-)
isomers, where the active, (-) isomer is levocetirizine. See Ex. 1015,
1:40–43 (disclosing that cetirizine is a racemic mixture of isomers where
“the active compound is the (-) isomer of 2-[4-[(4-chlorophenyl)-
phenylmethyl]-1-piperazinyl) ethoxyacetic acid, hereinafter referred to as
cetirizine”). US ’558 explains that “[t]he prefixes d and 1 or (+) and (-) are
employed to designate the sign of rotation of plane-polarized light by the
IPR2019-00400
Patent 8,633,194 B2

33
compound, with (-) or 1 meaning that the compound is levorotatory. A
compound prefixed with (+) or d is dextrorotatory.” Id. at 1:53–56.
US ’558 discloses the use of levocetirizine, i.e., “optically pure (-)
cetirizine for the treatment of seasonal and perennial allergic rhinitis in
humans while avoiding the concomitant liability of adverse effects
associated with the racemic mixture of cetirizine.” Id. at Abstract, 1:11–33,
3:47–62. According to the reference, levocetirizine may be administered,
e.g., orally or parenterally in a pharmaceutical composition. Id. at 6:56–67.
3. Analysis of Ground 2
Petitioner contends that in formulating a liquid pharmaceutical
composition of levocetirizine, one of ordinary skill in the art would have
focused on Example 5 of EP ’203, which comprises an ophthalmic solution
of cetirizine in combination with methylparaben and propylparaben. Pet. 43–
44 (citations omitted). Because US ’588 teaches that cetirizine comprises
two isomers, of which only the (-) isomer, levocetirizine, is active, Petitioner
asserts that one of ordinary skill in the art would have been motived to use
levocetirizine in place of cetirizine in such formulations. Id. at 46–48
(citations omitted). Petitioner further argues that one of ordinary skill in the
art would have been motivated to look to the Handbook for guidance
regarding the amount of parabens in various liquid formulations. Id. at 50.
For essentially the same reasons as set forth with respect to Ground 1,
discussed above, Petitioner asserts that the skilled artisan would have arrived
at the claimed ratio and amounts of methyl- and propylparaben set forth in
independent claim 1. See id. at 48–52.
IPR2019-00400
Patent 8,633,194 B2

34
According to Patent Owner, “Ground 2 is largely the same as Ground
1, except that Ground 2 uses two references (EP ’203 and US ’558) to teach
the point Petitioner draws from WO ’094 – a liquid pharmaceutical
composition of levocetirizine.” PO Resp. 52. Accordingly, Patent Owner
reasons that “Petitioner’s Ground 2 argument fails for the same reasons as
Ground 1.” Id. at 52–53.
Petitioner does not credibly dispute the similarity between its asserted
Grounds (see Reply 24–7) and we agree with Patent Owner’s assessment of
the similarity of Grounds 1 and 2. For the reasons forth in section
II(D)(3)(b), above, we remain unpersuaded by Dr. Laskar’s reasons for
calculating ranges for methyl- and propylparabens using methylparaben as a
starting point, as well as Petitioner’s explanation of why one of ordinary
skill in the art would have been motivated to use the low concentrations of
parabens recited in the claimed range.
We also credit Patent Owner’s argument that Petitioner has not
adequately explained why one of ordinary skill in the art would have
focused on Example 5 of EP ’203. PO Resp. 53–54. EP ’203 discloses eight
liquid cetirizine hydrochloride formulations. But according to Petitioner,
“Example 5 would have drawn the attention of the skilled artisan,” because
“only EP ’203’s Examples 5 (ophthalmic) and 7 (nasal) contain
preservatives.” Pet. 44 (citing Ex. 1002 ¶ 131). Petitioner’s expert further
asserts that he focused on Example 5 as opposed to Example 7 because it
was easier to convert to an oral formulation and “the relevant prior art relates
to preservation systems . . . that contain parabens, and not preservation
systems comprising benzalkonium.” Ex. 2010, 127:21–128:4; see PO Resp.
IPR2019-00400
Patent 8,633,194 B2

35
53–54 (citing Ex. 2010, 127:21–128:10, 129:1–130:16, 126:3–12).
Given that independent claim 1 is not limited to oral formulations, but
is broadly directed to a liquid pharmaceutical composition, we do not find
Dr. Laskar’s explanation persuasive. Nor are we persuaded by Dr. Laskar’s
implication that Example 7 is not relevant prior art insofar as it contains
benzalkonium as a preservative.
As is emphasized in Dr. Niazi’s testimony, it is unclear why
Dr. Laskar believes one of ordinary skill in the art would focus on the
examples in EP ’203 that contain preservatives, on formulations containing
parabens specifically, or on those that could be converted to oral solutions.
Ex. 2034 ¶¶ 213–214. Considering the evidence of record, we agree with
Patent Owner that Dr. Laskar’s selection of Example 5 relies upon
impermissible hindsight, which Petitioner does not rebut. See PO Resp.
53–54 (citing, e.g., Ex. 2034 ¶¶ 213–215; Ex. 2010, 131:24–132:5.). For this
additional reason Petitioner has not carried its burden to establish that the
challenged claims would have been obvious under Ground 2.
4. Conclusion as to Ground 2
For the above reasons Petitioner has not carried its burden to establish,
by a preponderance of the evidence, that the challenged claims are
unpatentable under Ground 2.
III. Patent Owner’s Motion to Exclude Evidence
Patent Owner moves to exclude Exhibits 1031–1038, 1040, 1041, and
1044, where Exhibits 1032–1037 and 1041 are excerpts from volumes 3 and
5 of Dr. Niazi’s Handbook of Pharmaceutical Manufacturing Formulations
IPR2019-00400
Patent 8,633,194 B2

36
(“the Niazi series”), Exhibit 1031 is compilation of formulations set forth in
those excerpts, and 1038, 1040, and 1044 were submitted “to establish the
publication date of Exhibits 1032–1037, or 1041, or of future, non-prior art
edition of the [Niazi series].” Paper 44, 5. Patent Owner bases its motion to
exclude on the proposition that, as excerpts, Exhibits 1032–1037 and 1041
are not “original writing[s] . . . required in order to prove [their] content”
under Federal Rule of Evidence 1002. Id. at 2–3.
Patent Owner’s motion is denied.
As set forth in its Response to the motion, Petitioner fairly used the
challenged exhibits as impeachment evidence in Dr. Niazi’s deposition. See
Paper 47, 1–3, 7–8. Patent Owner does not persuade us that, as excerpts, the
subject exhibits run afoul of Rule 1002. As a matter of practicality, the
Office, indeed adjudicative bodies in general, would be overwhelmed if
every exhibit purporting to be a book chapter, journal article, or dictionary
definition further included the entire volume or series from which it was
derived. Moreover, in the present case, Dr. Niazi, the sole author of the
Niazi series, did not question the accuracy or dispute that those subject
exhibits were true and accurate copies of his work. See id. at 7–8 (citing
Ex. 2034 ¶ 9; Ex. 1043 171:16–175:19). Having elicited testimony thereon,
we find that such testimony is best understood in the context of the exhibits
themselves.
Patent Owner further requests that we either accept its offer of proof
or take judicial notice of certain facts that it contends, “can be readily
ascertained from the testimony of Dr. Niazi.” Paper 44, 3–5 (citing Ex. 1043,
IPR2019-00400
Patent 8,633,194 B2

37
255:9–12). Given the apparent inaccessibility of the full Niazi series,14 and
our unwillingness to investigate the length and breadth of the entire six-
volume edition, we decline to take judicial notice of the asserted facts. In the
alternative, however, we acknowledge and reproduce below, Dr. Niazi’s
testimony which forms the basis for Patent Owner’s request:
Q: How many formulations are in your six series books?
A: If I remember correctly, there are 2,000.
Ex. 1043, 255:9–12. In light of the foregoing, we dismiss Patent Owner’s
offer of proof as moot.
IV. Petitioner’s Corrected Motion to Exclude Evidence
Petitioner moves, first, to exclude Dr. Niazi’s declaration (Exhibit
2034) in its entirety based on the premise that in failing to disclose the Niazi
series, Dr. Niazi “withheld material information, made affirmative
misrepresentations, and breached the requirements of 37 C.F.R.
§ 45.51(b)(1)(iii).” Paper 43, 1.
As an initial matter, Petitioner employed excerpts and summaries of
Dr. Niazi’s own work as deposition exhibits to challenge several of his
declaration statements. See, generally, Paper 43. Patent Owner responds that
Petitioner has not demonstrated any inconsistency between Dr. Niazi’s
declaration opinions and those exhibits or subsequent testimony. Paper 48,
2–7. We weighed these arguments and evidence in assessing Dr. Niazi’s

14 Petitioner indicates that although Dr. Niazi may have access to a personal
copy, many libraries have supplanted the prior art first edition of the Niazi
series with its second edition. Paper 43, 6; Paper 47, 10–11.
IPR2019-00400
Patent 8,633,194 B2

38
credibility and the parties’ positions as a whole.
With respect to the basis of Petitioner’s motion, however, we agree
with Patent Owner that Dr. Niazi did not withhold any part of the Niazi
series. As Patent Owner notes, the Niazi series is a publically available
reference; it presents a compilation of formulations from publically available
sources; its existence is disclosed in Dr. Niazi’s expert declaration; and it is
listed on the face of the’194 patent. Paper 48, 7–8 (citations omitted).
For at least these reasons, Petitioner’s motion to exclude Exhibit 2034
is denied on the merits.
Petitioner further moves to exclude Exhibits 2024, 2030, 2031 and
paragraphs 71–73 and 191–193 of Exhibit 2034, insofar as they rely on those
exhibits. Paper 48, 1; Paper 49, 5. Because we did not rely on that material
in our analysis, that portion of Petitioner’s motion is denied as moot.
V. Motions to Seal
We also address the parties’ motions to seal. Papers 18, 28 (by Patent
Owner); Papers 35 (by Parties jointly). Relevant to these motions, the Office
Patent Trial Practice Guide states:
3. A party intending a document or thing to be sealed may file a
motion to seal concurrent with the filing of the document or
thing. § 42.14. The document or thing will be provisionally
sealed on receipt of the motion and remain so pending the
outcome of the decision on motion.
4. Protective Orders: A party may file a motion to seal where the
motion contains a proposed protective order, such as the default
protective order in Appendix B. 37 C.F.R § 42.54. Specifically,
protective orders may be issued for good cause by the Board to
protect a party from disclosing confidential information.
IPR2019-00400
Patent 8,633,194 B2

39
37 C. F. R. § 42.54. Guidelines on proposing a protective order
in a motion to seal, including a Default Protective Order, are
provided in Appendix B. The document or thing will be protected
on receipt of the motion and remain so, pending the outcome of
the decision on motion.
Consolidated Office Patent Trial Practice Guide November 2019 (“CTPG”)
at 19–20.15
“There is a strong public policy for making all information filed in a
quasi-judicial administrative proceeding open to the public, especially in an
inter partes review which determines the patentability of claims in an issued
patent and therefore affects the rights of the public.” Garmin Int’l v. Cuozzo
Speed Techs., LLC, IPR2012–00001, Paper 34 at 1–2 (PTAB Mar. 14,
2013). For this reason, except as otherwise ordered, the record of an inter
partes review trial shall be made available to the public. See 35 U.S.C.
§ 316(a)(1); 37 C.F.R. § 42.14. Motions to seal may be granted for good
cause; until the motion is decided, documents filed with the motion shall be
sealed provisionally. See 37 C.F.R. §§ 42.14, 42.54(a). The moving party
bears the burden of showing that there is good cause to seal the record. See
37 C.F.R. § 42.20(c); see Argentum Pharm. LLC v. Alcon Research, Ltd.,
Case IPR2017-01053, Paper 27 (Jan. 19, 2018) (informative) (factors for
showing good cause to seal information).
As set forth in the CTPG, confidential information that is sealed
subject to a protective order ordinarily will become public 45 days after final
judgment in a trial. CTPG at 21–22. A party seeking to maintain

15 Available at
https://www.uspto.gov/sites/default/files/documents/tpgnov.pdf?MURL=
IPR2019-00400
Patent 8,633,194 B2

40
confidentiality of information may file a motion to expunge the information
before it becomes public; however, if the existence of the information is
identified in a final written decision following trial, there is an expectation
that the information will be made public. Id. at 22. This rule “balances the
needs of the parties to submit confidential information with the public
interest in maintaining a complete and understandable file history for public
notice purposes.” Id.
Under the Board’s procedures, there is an expectation that all exhibits,
including those filed under seal here, will be made part of the public record.
Furthermore, the public’s interest in understanding the basis for our decision
on patentability means that any good cause alleged in a motion to seal must
overcome this heightened public interest. Confidential information that is
subject to a protective order ordinarily becomes public 45 days after final
judgment in a trial. A party seeking to maintain the confidentiality of the
information may file a motion to expunge the information from the record
prior to the information becoming public. 37 C.F.R. § 42.56.
A. Patent Owner’s First Motion to Seal (Paper 18)
In Paper 18, Patent Owner moves to seal Exhibit 3005 pursuant to the
Board’s default protective order. Paper 18. According to Patent Owner,
“Exhibit 3005 discloses the nature of the relationship between Patent Owner
and Sanofi-Aventis with respect to the patent subject to this proceeding and
the product Xyzal 24HR®,” whereas, Exhibit 2008 is “a redacted,
non-confidential version of Exhibit 3005.” Id. at 1. Patent Owner avers that
Petitioner does not oppose the motion and that good cause exists in light of
IPR2019-00400
Patent 8,633,194 B2

41
“the nature of the relationship between Patent Owner and Sanofi-Aventis’
and the “competitively-sensitive, non-public, business information that is
itself subject to confidentiality obligations between Patent Owner and
Sanofi-Aventis.” Id. at 2.
Because the information redacted from Exhibit 3005 as compared to
Exhibit 2008 is not necessary to our Decision, we find that Patent Owner’s
desire to keep this information confidential is not outweighed by the public
interest in maintaining a complete and understandable record of these
proceedings. Accordingly, we grant Patent Owner’s motion with respect to
Exhibit 3005.
B. Patent Owner’s Second Motion to Seal (Paper 28).
In Paper 28, Patent Owner moves to seal Attachment A to the Parties’
Joint Stipulation Regarding the Deposition of Domenico Fanara (Paper 27).
Patent Owner Avers that Petitioner does not oppose the motion. Paper 28, 1.
According to Patent Owner,
Attachment A is an excerpted version of the deposition of
inventor Domenico Fanara which was taken in the related
district court litigation (UCB, Inc. et al. v. Apotex Inc., No.
0-18-cv-60846 (S.D. Fla.)). . . . [and] discloses certain
confidential information subject to the district court protective
order. Specifically, the deposition testimony contains
(1) information relating to a strategic partnership with a
pharmaceutical company not party to this proceeding and
(2) details regarding Patent Owner’s pharmaceutical
formulations.
Paper 28, 1. Patent Owner further states that the information sought to be
protected “does not relate to the patentability of claims in an issued patent or
IPR2019-00400
Patent 8,633,194 B2

42
otherwise affect the rights of the public,” and that a parallel version of Paper
27 containing a minimally-redacted version of Attachment A is of record as
Paper 26. Id.
Considering the Patent Owner’s representation as to nature of the
information sought to be protected, and that we do not rely on this
information in our Decision, Patent Owner has sufficiently shown good
cause for granting this request. We find Patent Owner’s desire to keep this
information confidential is not outweighed by the public interest in
maintaining a complete and understandable record of these proceedings.
Interpreting Patent Owner’s motion as a request to seal Paper 28 in its
entirety, Patent Owner’s request is granted.
C. The Parties’ Joint Motion to Seal (Paper 35).
Although Paper 35 is submitted jointly by the parties, we understand
that Patent Owner seeks to seal confidential, non-public versions of Exhibits
1039, 1042, 1043, and Paper 33 (“Petitioner’s Reply to Patent Owner’s
Complete Response”), whereas Petitioner “takes no position, one way or
another, on Patent Owner’s position” and notes that all redactions in the
corresponding public versions “were made or approved by Patent Owner.”
See e.g., Paper 35, 1, 4. We address the subject documents as follows:
1. Exhibit 1039
According to the motion, Exhibit 1039 is the exhibit labeled version
of the Deposition of Domenico Fanera and is thus, substantially identical to
Attachment A to Paper 28, addressed in the section above. Having already
considered this document in the context of Paper 28, the request is granted.
IPR2019-00400
Patent 8,633,194 B2

43
2. Exhibits 1042, 1043, and Paper 33
Petitioner filed confidential and non-confidential versions of Exhibits
1042 and 1043. Petitioner filed Paper 33 as restricted to be viewed by Board
and Parties Only and concurrently filed a redacted, public version entered as
Paper 34. With respect to Exhibits 1042 and 1043, Patent Owner takes the
position that the redacted portions “relate to confidential information which
would reveal details of Patent Owner’s confidential pharmaceutical
formulations.” Paper 35, 3–4. With respect to Petitioner’s Reply, Patent
Owner further asserts that the redacted portions “may be found in exhibits
which Patent Owner has requested be sealed in this matter for the same
reason.” Id. at 4.
The request to seal Exhibits 1042, 1043, and Paper 33 is denied.
Patent Owner’s terse explanation for why sealing is appropriate is
insufficient to determine whether good cause exists to grant the request. Nor
is this panel inclined to play seek and find with the record or substitute its
judgment on precisely what information Patent Owner considers
confidential.
Patent Owner is welcome to renew its request, jointly or upon
consultation with Petitioner, within 10 business days of this Decision. Any
such request shall be accompanied by a statement that the information
sought to be redacted is not cited, directly or indirectly, in this Decision. To
the extent such statement cannot be made, Patent Owner shall propose a
substitute version of the affected Exhibit(s) and provide an explanation of
any differences.
IPR2019-00400
Patent 8,633,194 B2

44
VI. CONCLUSION
For the foregoing reasons, Petitioner has not shown by a
preponderance of the evidence that any of the challenged claims of the ’194
Patent are unpatentable, as summarized in the following table:
Claims 35 U.S.C § Reference(s)/Basis
Claims
Shown
Unpatentable
Claims Not
Shown
Unpatentable
1–11 103(a) Handbook, WO ’094 1–11
1–11 103(a)
Handbook,
EP ’203,
US ’558
1–11
Overall
Outcome 1–11

IPR2019-00400
Patent 8,633,194 B2

45
VII. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that claims 1–11 of U.S. Patent No. 8,633,194 B2 are not
determined to be unpatentable;
FURTHER ORDERED that Paper 44, Patent Owner’s Motion to
Exclude Exhibits 1031–1038, 1040, 1041, and 1044 is denied;
FURTHER ORDERED that Paper 43, Petitioner’s Corrected Motion
to Exclude Exhibits 2024, 2030, 2031, and 2034 is denied;
FURTHER ORDERED that Paper 18, Patent Owner’s First Motion to
Seal is granted as to Exhibit 3005;
FURTHER ORDERED that Paper 28, Patent Owner’s Second Motion
to Seal is granted as to Paper 27;
FURTHER ORDERED that Paper 35, the Parties’ Joint Motion to
Seal is granted as to Exhibit 1039 only;
FURTHER ORDERED that Paper 35, the Parties’ Joint Motion to
Seal is denied as to Exhibits 1042, 1043, and Paper 33 with leave to renew
the request as set forth in section V(C)(2), above;
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.

IPR2019-00400
Patent 8,633,194 B2

46

For PETITIONER:

Jitendra Malik
Alissa Pacchioli
Joseph Janusz
Lance Soderstrom
KATTEN MUCHIN ROSENMAN LLP
jitty.malik@kattenlaw.com
alissa.pacchioli@kattenlaw.com
joe.janusz@kattenlaw.com
lance.soderstrom@kattenlaw.com

For PATENT OWNER:

James Trainor
Robert Counihan
Erica Sutter
FENWICK & WEST LLP
jtrainor@fenwick.com
rcounihan@fenwick.com
esutter@fenwick.com