Trials@uspto.gov
`571-272-7822
`
`
`Paper 13
`Date: May 18, 2022
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SLAYBACK PHARMA LLC,
`Petitioner,
`v.
`EYE THERAPIES, LLC,
`Patent Owner.
`
`IPR2022-00142
`Patent 8,293,742 B2
`
`
`
`
`
`
`
`
`
`Before JOHN G. NEW, TINA E. HULSE, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`NEW, Administrative Patent Judge.
`
`DECISION
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314, 37 C.F.R. § 42.4
`
`
`
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`
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`571-272-7822
`
`
`Paper 13
`Date: May 18, 2022
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SLAYBACK PHARMA LLC,
`Petitioner,
`v.
`EYE THERAPIES, LLC,
`Patent Owner.
`
`IPR2022-00142
`Patent 8,293,742 B2
`
`
`
`
`
`
`
`
`
`Before JOHN G. NEW, TINA E. HULSE, and
`ROBERT A. POLLOCK, Administrative Patent Judges.
`NEW, Administrative Patent Judge.
`
`DECISION
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314, 37 C.F.R. § 42.4
`
`
`
`
`
`
`
`
`
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`IPR2022-00142
`Patent 8,293,742 B2
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`
`I. INTRODUCTION
`Slayback Pharma, LLC (“Petitioner”) has filed a Petition requesting
`inter partes review of claims 1–6 of U.S. Patent No. 8,293,742 B2
`(Ex. 1001, “the ’742 patent”). Paper 2 (“Pet.”). Eye Therapies, LLC.
`(“Patent Owner”) filed a Preliminary Response to the Petition. Paper 7
`(“Prelim. Resp.”). With our authorization filed a Reply to Patent Owner’s
`Preliminary Response and Patent Owner filed a Sur-Reply. Papers 10, 12.
`Under 35 U.S.C. § 314, the Board “may not authorize an inter partes
`review to be instituted unless … the information presented in the petition
`… and any response … shows that there is a reasonable likelihood that the
`petitioner would prevail with respect to at least 1 of the claims challenged in
`the petition.” Upon consideration of the Petition and Preliminary Response,
`and the evidence of record, we determine that the evidence presented
`demonstrates a reasonable likelihood that Petitioner would prevail in
`establishing the unpatentability of at least one of the challenged claims of
`the ’742 patent. Accordingly, we institute inter partes review of claims 1–6
`of the ’742 patent.
`
`
`II. BACKGROUND
`A. Real Parties in Interest
`Petitioner identifies itself and Slayback Pharma India LLP as the real
`parties-in-interest. Pet. 65. Patent Owner identifies itself and Bausch &
`Lomb, Inc. and Bausch & Lomb Ireland Limited as the real parties-in-
`interest. Paper 4, 2.
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`B. Related Matters
`Petitioner states that the ’742 patent has been asserted in pending civil
`action Bausch & Lomb Inc. et al. v. Slayback Pharma LLC et al., 3:21-cv-
`16766 (D.N.J.). Ex. 2006. Pet. 65. Patent Owner adds that the ’742 patent
`has also been asserted in Bausch & Lomb, Inc, et al. v. Harrow Health, Inc.
`et al., 3:21-cv-19252 (D.N.J.). Paper 4, 2.
`Petitioner also filed a petition for inter partes review of U.S. Patent
`No. 9,259,425 in IPR2022-00146.
`
`The Asserted Grounds of Unpatentability
`C.
`Petitioner contends that claims 1–6 of the ’742 patent are
`
`unpatentable, based upon the following grounds:
`Claim(s) Challenged 35 U.S.C. §
`Reference(s)/Basis
`1–2
`102
`Gil1
`1–2
`102
`Walters2
`
`
`1 Gil et al. (US 6,294,553 B1, September 25, 2001) (“Gil”). Ex. 1004.
`
` 2
`
`
`
`
`
` T.R. Walters et al., A Pilot Study of the Efficacy and Safety of AGN
`190342-LF 0,02% and 0.08% in Patients with Elevated Intraocular
`Pressure, 32(4) ASSOC. RES. VISION AND OPHTHALMOL. 988 (1991)
`(“Walters”). Ex. 1005.
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`3
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`Claim(s) Challenged 35 U.S.C. §
`1–6
`103
`
`
`
`Reference(s)/Basis
`Gil, Norden3, Dean4, Alphagan5, and
`Federal Register6
`
`Petitioner also relies upon the Declarations of Dr. Neal A. Sher (the
`“Sher Declaration,” Ex. 1002) and Dr. Paul A. Laskar (the “Laskar
`Declaration,” Ex. 1003).
`
`D. The ’742 Patent
`The ’742 patent is directed to compositions and methods for
`
`preferential vasoconstriction of smaller blood vessels relative to larger blood
`vessels. Ex. 1001 Abstr., col. 2, ll. 47–48. The compositions are
`administered to patients with ocular conditions, resulting in the reduction
`eye redness. Id. at col. 12, ll. 14–59.
`
`In one embodiment, a selective α-2 adrenergic receptor agonist is
`administered to reduce vasoconstriction at a concentration below about
`0.05% weight by volume. Ex. 1001, col. 5, ll. 19–26. The α-2adrenergic
`receptor agonist preferably has a binding affinity 100-fold to 500-fold or
`greater for α-2adrenergic receptors than a-1 adrenergic receptors. Id. at col.
`
`
`3 R.A. Norden, Effect of Prophylactic Brimonidine or Bleeding
`Complications and Flap Adherence after Laser in Situ Keratomileusis.
`18(4) J. Refractive Surg. 468–471 (2002) (“Norden”). Ex. 1006.
`
` 4
`
` 5
`
` 6
`
`
`
` Dean et al. (US 6,242,442 B1, June 5, 2001) (“Dean”). Ex. 1007.
`
` ALPHAGAN® (brimonidine tartrate ophthalmic solution) 0.2%.
`Physicians’ Desk Reference, 52th ed., Medical Economics Company, Inc.,
`487 (1998) (“Alphagan”). Ex. 1008.
`
` 53 Fed. Reg. 7076–7093 (Mar. 4, 1988) (“Federal Register”). Ex. 1009.
`4
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`5, ll. 20–25, 46–48. The preferred α-2adrenergic receptor agonist is
`brimonidine. Id. at col. 5, ll. 52–55; cols. 5–6, ll. 65–4.
`
`E.
`
`Illustrative Claim
`Independent claim 1 of the ’742 patent is representative of the
`challenged claims and recites:
`
`E.
`
`A method for reducing eye redness consisting essentially of
`administering brimonidine to a patient having an ocular
`condition, wherein brimonidine is present at a concentration
`between about 0.001% weight by volume and about 0.05%
`weight by volume.
`Ex. 1001, col. 22, ll. 17–22.
`
`Prosecution History of the ’742 Patent
`The ’742 patent issued from U.S. Application 12/460,941 (the “‘941
`Application”) filed on July 27, 2009 and claims the priority benefit of
`provisional Application Ser. No. 61/207,481, which was filed on February
`12, 2009; provisional Application Ser. No. 61/203,120, filed on December
`18, 2008; provisional Application Ser. No. 61/192,777, filed on September
`22, 2008; and provisional Application Ser. No. 61/137,714 filed on August
`1, 2008. Ex. 1001, code (60).
`The claims of the ’742 patent, including claims 1–6, were allowed on
`October 23, 2012. Id., code (45).
`
`III. Analysis
`
`A. Claim Construction
`The Board applies 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
`
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`C.F.R. § 100(b) (2020). Under that standard, claim terms “are generally
`given their ordinary and customary meaning” as understood by a person of
`ordinary skill in the art at the time of the invention. Phillips v. AWH Corp.,
`415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc). “In determining the
`meaning of the disputed claim limitation, we look principally to the intrinsic
`evidence of record, examining the claim language itself, the written
`description, and the prosecution history, if in evidence.” DePuy Spine, Inc.
`v. Medtronic Sofamor Danek, Inc., 469 F.3d 1005, 1014 (Fed. Cir. 2006)
`(citing Phillips, 415 F.3d at 1312–17). Extrinsic evidence is “less significant
`than the intrinsic record in determining ‘the legally operative meaning of
`claim language.’” Phillips, 415 F.3d at 1317 (quoting C.R. Bard, Inc. v. U.S.
`Surgical Corp., 388 F.3d 858, 862 (Fed. Cir. 2004)).
`Petitioner proposes construction of two terms: “about 0.025%” and
`“ocular condition.” Pet. 26–31. Patent Owner disputes Petitioner’s
`arguments regarding the first term. Prelim. Resp. 29–36. Patent Owner does
`not take a position regarding the latter term. Prelim. Resp. 36.
`
`
`“about 0.025%”
`1.
`Petitioner urges us to construe the claim term “about 0.025%” as
`including 0.03%. Pet. 26–27. According to Petitioner, the language of the
`claims, the Specification of the ’742 patent, and the prosecution history
`provide no explicit disclosures as to whether “about 0.025%” includes or
`excludes “0.03%.” Pet. 27 (citing Ex. 1003 ¶ 63). Consequently, argues
`Petitioner, whether “about 0.025%” includes 0.03%, “must be interpreted in
`its technologic and stylistic context” and depends upon “the criticality of the
`[numerical limitation] to the invention.” Id. at 27–28 (quoting Cohesive
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`Techs. v. Water Corp., 543 F.3d 1351, 1368 (Fed. Cir. 2008). Moreover,
`“[t]he relevant inquiry ‘is the purpose of the limitation in the claimed
`invention.” Id. at 34 (quoting Cohesive, 543 F.3d at 1368).
`
`Petitioner points to six disclosures of the ’742 patent that support its
`contention that “about 0.025%” includes “0.03%.” First, Petitioner points
`to the Abstract of the ’742 patent, which states that its invention is directed
`to “low concentrations” of brimonidine, which the Specification defines as
`“concentrations from between about 0.0001% to about 0.05%; more
`preferably, from about 0.001% to about 0.025%; even more preferably, from
`about 0.01% to about 0.025%; and even more preferably, from about 0.01%
`to about 0.02% weight by volume.” Id. at 28 (quoting Ex. 1001 col. 3, ll.
`61–65, and citing Ex. 1003 ¶ 65).
`
`Second, argues Petitioner, the Specification identifies concentration
`ranges that from 0.010% and 0.015% to about 0.05% brimonidine as
`“preferred” embodiments. Pet. 29 (citing Ex. 1001, col. 12, ll. 60–63, col.
`14, ll. 14–16; Ex. 1003 ¶ 66). Petitioner also notes that the Specification
`identifies brimonidine as a “selective a-2 agonist” and that in a “preferred
`embodiment” the concentration of the “the selective a-2 adrenergic receptor
`agonist” is in a range up to “about 0.035%.” Id. (quoting Ex. 1001, col. 5, ll.
`52–54, col. 9, ll. 14-16, and citing Ex. 1003 ¶ 67).
`
`Third, Petitioner points to Figure 4E of the Specification, which
`depicts the left eye of a patient “after being treated with a composition of the
`present invention comprising brimonidine at 0.033%.” Pet. 30 (quoting Ex.
`1001, col. 3, ll. 30-33, Fig. 4E). Petitioner notes that the Specification states
`that the application of 0.033% brimonidine did not result in rebound
`
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`hyperemia, an asserted problem in the prior art. Id. (citing Ex. 1001, col. 20,
`ll. 17–19, Ex. 1003 ¶ 69).
`
`Fourth, and relatedly, Petitioner asserts that brimonidine is “a known
`selective alpha 2 agonist [] associated with significant rebound hyperemia
`(primary or delayed onset vasodilation) in its current concentration range for
`treating glaucoma of about 0.1% to 0.2%.” Pet. 30 (citing Ex. 1001, col. 2,
`ll. 2–8; Ex. 1003 ¶ 70). Petitioner argues that a person of ordinary skill in
`the art would understand that, compared to the recited prior art range of
`“about 0.1% to 0.2%,” a concentration of “0.03%” accomplishes a reduction
`in brimonidine concentration that “is the purpose of the limitation in the
`claimed invention.” Id. (quoting Cohesive, 543 F.3d at 1368).
`
`Fifth, Petitioner argues that the Specification does not disclose that
`keeping the brimonidine concentration below 0.03% is critical, and notes
`that Figure 2 shows that a concentration of 0.03% is included in the range
`where net vasoconstriction benefits” are the highest. Pet. 30 (citing Ex.
`1001, Fig. 2; Ex. 1003 ¶ 71).
`
`Sixth, Petitioner asserts that, from the perspective of a pharmaceutical
`formulator, “about 0.025%” includes 0.03% because, as the upper limit of a
`range, “about 0.025%,” rounded to two decimal points, is “0.03%”. Pet. 31
`(citing Ex. 1003 ¶ 72). Petitioner contends that a skilled artisan would
`expect, in the context of the ’742 patent, that it would be difficult to
`distinguish between the clinical effect of 0.025% and 0.03% brimonidine.
`Id.
`Patent Owner argues that the Specification of the ’742 patent
`
`separately discloses concentrations of “about 0.025%” and “about 0.03%”
`within the broader concentration range of less than 0.05% brimonidine.
`
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`Prelim. Resp. 30. Patent Owner notes that, in two successive paragraphs, the
`Specification discloses using in related applications “about 0.001% to about
`0.025%” brimonidine and “about 0.001% to about 0.03%” brimonidine. Id.
`(quoting Ex. 1001, col. 8, ll. 46–55, 56–63, also citing Ex. 1001, Ex. 3
`(describing the use of a composition containing 0.03% brimonidine)).
`According to Patent Owner, a person of ordinary skill in the art would
`understand that, because the concentrations are separately described,
`“about 0.025%” is not the same as “about 0.03%.” Id.
`
`Furthermore, argues Patent Owner, the Specification discloses that
`brimonidine at a concentration of 0.025% reduces redness without
`significant rebound hyperemia (that is, the development of redness in an eye
`after a temporary occurrence of whitening). Prelim Resp. 31 (citing Ex.
`1001, cols. 13–14, ll. 65–5, col. 14, ll. 23–31, col. 9, ll. 20-24). Patent
`Owner asserts that the ’742 Specification thus effectively draws a further
`distinction between “about 0.025%” and 0.03% brimonidine by noting that
`rebound hyperemia begins to increase at a concentration of brimonidine
`around 0.03%. Id. (citing Ex. 1001, col. 19, ll. 52–54).
`
`“When ‘about’ is used as part of a numeric range, the use of the word
`“‘about’” avoids a strict numerical boundary to the specified parameter.”
`Cohesive, 543 F.3d at 1368 (internal quotations omitted). When “about” is
`used to define the limit of a numerical range, the extension beyond the stated
`number depends on what “a person having ordinary skill in the art … would
`reasonably consider ‘about …’ to encompass.” Monsanto Tech. LLC v. E.I.
`DuPont de Nemours & Co., 878 F.3d 1336, 1342 (Fed. Cir. 2018).
`Furthermore, when determining how far beyond the claimed range the term
`“about” extends the claim, “[w]e must focus ... on the criticality of the
`
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`[numerical limitation] to the invention.” Ortho–McNeil Pharm., Inc. v.
`Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1327 (Fed. Cir. 2007).
`“Extrinsic evidence of meaning and usage in the art may be helpful in
`determining the criticality of the parameter.” Id. at 1326 (quoting Pall Corp.
`v. Micron Separations, Inc., 66, F.3d 1211, 1217 (Fed. Cir. 1995)).
`At this stage of the proceeding, and on this record, we find
`Petitioner’s reasoning that the claim term “about 0.025%” includes 0.03% to
`be more persuasive. As Petitioner points out, the Specification discloses a
`number of embodiments with concentration ranges of brimonidine that
`include both values. Furthermore, Patent Owner has not persuasively
`pointed to any disclosures of the ’742 patent that expressly support the
`criticality of 0.025% brimonidine as the upper end of the concentration
`range. Indeed, the passage pointed to in this respect by Patent Owner states:
`FIG. 6 depicts a graphical representation of a finding of the
`present invention that an increased rebound hyperemia begins at
`around 0.03% for brimonidine. It thus demonstrates that the net
`effectiveness of brimonidine as a decongestant is greatest
`between about 0.01% and about 0.03%; preferably, between
`about 0.012% and about 0.02%.
`
`Ex. 1001, col. 19, ll. 52–57. This passage does not expressly or implicitly
`disclose the criticality of “about 0.025%” as the upper limit of the effective
`range of brimonidine concentration.
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`Figure 6 of the ’742 patent is reproduced below:
`
`
`Figure 6 of the ‘’742 patent depicts a graph entitled “Feasability
`C% Determination.”
`
`
`Despite being labeled “Feasability C% Determination,” Figure 6 has
`no legend explaining what the various line plots represent or what the oval is
`highlighting. Patent Owner relies on the teaching that Figure 6 demonstrates
`that increased rebound hyperemia “begins at around 0.03% for
`brimonidine.” Prelim. Resp. 26. But it is unclear which illustrated function
`of Figure 6 supports that assertion, and the Specifications of those patent
`applications do not explain, either.
`As further evidence that “about 0.025%” does not exclude 0.03%
`brimonidine, Figure 4E of the references cited by Patent Owner illustrates
`that, four hours after a third application of a concentration of 0.033%
`brimonidine, there is no indication of rebound hyperemia. See, e.g., Ex.
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`2021, Fig. 4e, ¶ 186. This therefore suggests that increased hyperemia may
`not necessarily occur until the brimonidine concentration exceeds 0.03%.
`Finally, absent expert testimony to the contrary, we credit the
`testimony of Dr. Laskar who opines that a person of ordinary skill in the art
`would understand that “about 0.025%” includes 0.03% because of rounding
`and because it would be difficult to distinguish between the clinical effect of
`“about 0.025%” and 0.03%. Ex. 1003 ¶ 70.
`
`Because Petitioner has persuasively argued that a person of ordinary
`skill in the art would not recognize any criticality of the five-thousandths
`weight percentile difference between 0.025% and 0.03% from the teachings
`of the ’742 Specification, for the purposes of this Decision, we construe the
`claim term “about 0.025%” as including “0.03%.”
`
`
`“ocular condition”
`2.
`Petitioner argues that the ’742 patent defines “ocular condition”
`
`broadly and without limitation. Pet. 31 (citing Ex. 1001, col. 12, ll. 14–49).
`Petitioner therefore urges us to construe “ocular condition” as including,
`without limitation eye redness, glaucoma (including open-angle glaucoma);
`elevated intraocular pressure, also known as ocular hypertension,
`postoperative reduction of subconjunctival hemorrhage and hyperemia after
`refractive surgery such as LASIK and radial keratotomy, subconjunctival
`hemorrhage and hyperemia prophylaxis prior to refractive surgery such as
`LASIK and radial keratotomy, and redness in the eye following LASIK or
`radial keratotomy. Id. (citing Ex. 1001, col. 12, ll. 14–49; Ex. 1002 ¶ 47).
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`Patent Owner makes no argument with respect to construction of this
`
`claim term, other than to note that the phrase would be understood by a
`skilled artisan to have its ordinary meaning consistent with the Specification.
`
`Given the capacious disclosures of the Specification of the ’742 patent
`in this respect, we find Petitioner’s proposed construction to be reasonable.
`See Ex. 1001, col. 12, ll. 14–52. We consequently construe, for the purposes
`of this Decision, the claim term “ocular condition” as including, without
`limitation, “eye redness, glaucoma (including open-angle glaucoma);
`elevated intraocular pressure, also known as ocular hypertension,
`postoperative reduction of subconjunctival hemorrhage and hyperemia after
`refractive surgery such as LASIK and radial keratotomy, subconjunctival
`hemorrhage and hyperemia prophylaxis prior to refractive surgery such as
`LASIK and radial keratotomy, and redness in the eye following LASIK or
`radial keratotomy.”
`
`Additional claim construction
`3.
`
`Reviewing the present record, the panel the panel concludes that no
`
`other claim term needs express construction for the purposes of this
`Decision. See Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co.,
`868 F.3d 1013, 1017 (Fed. Cir. 2017) (per curiam) (claim terms need to be
`construed “only to the extent necessary to resolve the controversy” (quoting
`Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir.
`1999))).
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`B. A Person of Ordinary Skill in the Art
`Petitioner contends that a person of ordinary skill in the art would
`have been a composite person (or team) that included a medical doctor and a
`pharmaceutical formulator. Pet. 15 (citing Ex. 1002 ¶ 26; Ex. 1003 ¶ 29).
`Petitioner asserts that the medical doctor would have been an
`ophthalmologist with at least three to four years of experience in LASIK
`surgery, clinical trials, and U.S. FDA regulation of eye products, and had
`experience in the use of topical brimonidine, apraclonidine; and topical
`vasoconstrictors such as naphazoline and tetrahydrozoline. Id. (citing Ex.
`1002 ¶ 26). Petitioner contends that the pharmaceutical formulator would
`have had a doctoral degree in pharmaceutics, or a related degree, and at least
`three to five years of experience developing eye drop formulations for
`clinical trial and regulatory approval. Id. (citing Ex. 1003 ¶ 29).
`Patent Owner does not contest this definition in its Preliminary
`Response, stating it does not take a position at this time regarding the
`qualifications of the person of ordinary skill in the art. Prelim. Resp. 29.
`Patent Owner further notes that Petitioner’s characterization of a person of
`ordinary skill in the art goes beyond that of ordinary skill. Id.
`We find Petitioner’s proposed characterization to be reasonable and
`consequently adopt Petitioner’s definition for the purposes of this Decision.
`
`C. Ground I: Alleged Anticipation of Claims 1–2 by Gil
`1. Overview of Gil (Ex. 1004)
`Gil was published September 25, 2001, and issued from US Appl. Ser.
`No. 09/783,160 filed on February 14, 2001. Ex. 1004, code 21, 22. Gil
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`claims the priority benefit of provisional application Ser. No. 60/182,609,
`filed on February 15, 2000. Id. at code 60.
`Gil is directed to:
`A method for alleviating ocular surface pain in a mammalian eye
`comprising administering to a mammalian eye having ocular
`surface pain an amount of brimonidine effective to alleviate the
`ocular surface pain.
`Id., claim 1.
`Gil teaches that an effective dose of brimonidine to provide ocular pain
`relief is between 0.01% and 0.5%. Ex. 1004, col. 3, ll. 46–49. Gil further
`teaches that brimonidine relieves pain associated with corneal injuries, and
`that ocular responses characteristic of neurogenic inflammation, include
`redness and pupillary constriction. Id. at col. 2, ll. 52–54, col. 5, ll. 38–39.
`
`
`2. Anticipation of Claims 1–2 by Gil: Petitioner’s Contentions
`a.
`Claim 1
`Petitioner argues that the disclosures of Gil anticipate each of the
`limitations of claims 1–2. Pet. 32–36.
`
`i.
`
`[1.P] A method for reducing eye redness
`
`Petitioner argues that Example 1 of Gil discloses administration of
`0.03% brimonidine is inherently a method “for reducing eye redness.” Pet.
`34 (citing Ex. 1002 ¶ 55 (“Whether intended or not, the administration of
`0.03% brimonidine to the radial keratotomy patients in Example 1 of [Gil] is
`a method for reducing eye redness”)).
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`ii.
`
`[1.1] “consisting essentially of administering
`brimonidine”
`
`
`Petitioner contends that Example 1 of Gil compares administration
`
`“brimonidine and placebo”: brimonidine is the only drug identified. Pet. 34
`(citing Ex.1004, col. 4, ll. 46–47; Ex. 1002 ¶ 57). Petitioner also notes that
`Example 1 of Gil also discloses that “brimonidine is administered as a
`0.03% ophthalmic solution” and that the “preferred vehicle” of Gil “is
`purified water.” Id. at 35 (citing Ex. 1004, col. 4, ll. 52–53, col. 4, ll. 4–5;
`Ex. 1003 ¶ 77). Petitioner asserts that, in the context of a vasoconstrictor
`eye drop this indicates “consisting essentially of brimonidine.” Id.
`
`
`iii.
`
`[1.2] “to a patient having an ocular condition”
`
`
`Petitioner contends that a person of ordinary skill in the art would
`
`have understood “ocular condition” to include, without limitation,
`postoperative reduction of subconjunctival hemorrhage and hyperemia after
`LASIK and radial keratotomy, subconjunctival hemorrhage and hyperemia
`prophylaxis prior to LASIK and radial keratotomy, and redness in the eye
`following LASIK or radial keratotomy. Pet. 35 (citing Ex. 1001, col. 12, ll.
`14–49; Ex. 1002 ¶ 58). Petitioner argues that administration of brimonidine
`in Example 1 of Gil to refractive surgery patients discloses this limitation.
`Id. (citing Ex. 1004, Ex. 1, Ex. 1002 ¶ 59).
`
`
`
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`IPR2022-00142
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`
`iv.
`
`[1.3] “wherein brimonidine is present at a
`concentration between about 0.001% weight by
`volume and about 0.05% weight by volume”
`
`
`Petitioner asserts that concentrations disclosed by Gil are weight per
`
`unit volume. Pet. 35 (citing Ex. 1004, col. 3, ll. 48; Ex. 1003 ¶¶ 78–79.
`Petitioner contends that a skilled artisan would have understood the 0.03%
`solution in Example 1 of Gil as “weight by volume.” Id. at 36 (citing Ex.
`1003 ¶¶ 78–79). Petitioner further argues that, given brimonidine’s
`solubility, it would have been routine to formulate a brimonidine solution
`anywhere in the range from 0.001% to 0.05%. Id. (citing Ex. 1033, Tables I,
`II; Ex. 1003 ¶¶ 102–103).
`
`Claim 2
`b.
`
`Claim 2 depends from claim 1, and Petitioner incorporates the
`
`arguments made with respect to claim 1 by reference into claim 2. Pet. 36
`
`
`i.
`
`[2.1] “wherein brimonidine is present at a
`concentration between about 0.001% to about 0.025%
`weight by volume”
`
`
`Petitioner argues that “between about 0.001% to about 0.025% weight
`
`by volume,” includes “0.03%,” as taught by Example 1 of Gil. Pet. 36
`(citing Ex. 1004, col. 4, ll. 48–52; Ex. 1003 ¶ 73; see also Section III.A.1
`supra).
`
`
`Patent Owner’s Preliminary Response
`3.
`Patent Owner responds that Gil is directed to the use of brimonidine to
`
`treat ocular pain. Prelim. Resp. (citing, e.g., Ex. 1004, Title, Abstr.). With
`
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`respect to Petitioner’s contention that Gil inherently discloses eye redness
`reduction, Patent Owner argues that, to establish inherent anticipation, the
`Petitioner must prove that all of the elements of claims 1 and 2 necessarily
`and inevitably flow from the elements explicitly disclosed by Example 1.
`Id. at 37 (citing Endo Pharm. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374,
`1381 (Fed. Cir. 2018); Galderma Labs., L.P. v. Teva Pharms. USA, Inc., 799
`F. App’x 838, 845 (Fed. Cir. 2020)). Petitioner asserts that, because
`Example 1 is silent as to redness reduction, or even whether the subjects had
`redness in the first place, the Petitioner’s argument rests entirely on mere
`“probabilities or possibilities,” which cannot establish anticipation. Id.
`(citing Ex. 1004, cols. 4–5, ll. 66–2; also citing Bettcher Indus., Inc. v. Bunzl
`USA, Inc., 661 F.3d 629, 639 (Fed. Cir. 2011) (citing In re Oelrich, 666 F.2d
`578, 581 (C.C.P.A. 1981).
`
`Patent Owner argues further that, because there is no basis in Example
`1 to conclude that the patients undergoing unilateral radial keratotomy had
`eye redness, the Petitioner relies on a reference describing a different study,
`with different patients undergoing LASIK. Prelim. Resp. 39 (citing Pet. 33–
`34 (citing Ex. 10257)). However, argues Patent Owner, a 2013 study on
`patients with different ocular maladies cannot inform one of anything
`regarding the condition of the entirely different patient population in
`Example 1 of Gil. Id.
`
`
`7 T.A. Pasquali, Dilute Brimonidine to Improve Patient Comfort and
`Subconjunctival Hemorrhage After LASIK, 29(7) J. REFRACT. SURG. 469–
`75 (2013) (Ex. 1025).
`
`
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`Patent Owner also argues that Example 1 of Gil administered
`
`brimonidine at a concentration of 0.03%, whereas Claim 2 recites a
`concentration of “about 0.025%” brimonidine at its upper limit, which
`does not include 0.03%. Prelim Resp. 39.
`
`3. Analysis
`We find that Petitioner has established a reasonable likelihood of
`prevailing at trial, and that Patent Owner’s arguments are insufficient to
`overcome that likelihood.
`As an initial matter, we have already explained why we construe, for
`the purposes of this Decision, the claim term “about 0.025%” includes
`0.03%. See Section III.A.1. supra. Patent Owner’s argument that Gil does
`not teach “about 0.025%” is therefore not persuasive for purposes of this
`Decision.
`A claim is unpatentable under 35 U.S.C. § 102 only when “every
`element and limitation of the claim was previously described in a single
`prior art reference, either expressly or inherently, so as to place a person of
`ordinary skill in possession of the invention.” Sanofi-Synthelabo v. Apotex,
`Inc., 550 F.3d 1075, 1082 (Fed. Cir. 2008). With respect to Petitioner’s
`argument that Gil inherently discloses the preambular limitation reciting a
`“method for reducing eye redness,” we agree that, although Gil teaches that
`“[o]cular responses characteristic of neurogenic inflammation, including
`redness and pupillary constriction, are also observed in rabbits following
`external stimuli,” Example 1 of Gil does not expressly teach that
`administration of 0.03% brimonidine reduces redness in the subject patients.
`See Ex. 1004, col. 5, ll. 38–40.
`
`
`
`19
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`
`Nevertheless, we do not agree with Patent Owner that Gil teaches only
`the reduction of ocular pain via administration of brimonidine in the claimed
`concentrations. Gil discloses that a person of skill in the art would
`understand that inflammation of the eye is accompanied by both redness and
`pain, and expressly discloses that its invention is directed to “the topical
`application of brimonidine for treating ocular pain and neurogenic
`inflammation.” Id. at col. 1, ll. 11–13. Gil also discloses that
`“neuropeptides enhance inflammatory reactions in the injured tissue,
`contributing to vasodilation, edema, and increased vascular permeability,
`this phenomenon is called ‘neurogenic inflammation.’” Id. at col. 1, ll. 40–
`43. We find that a skilled artisan would understand that “neurogenic
`inflammation,” and particularly “vasodilation, edema, and increased
`vascular permeability” are proximal causes of eye redness. See id. at col. 5,
`ll. 38–40.
`Furthermore, and as Petitioner argues, the ’742 Specification also
`expressly teaches that administration of doses of brimonidine of 0.02–
`0.033% resulted in redness reduction. See Ex. 1001, cols. 19–20, ll. 65–25.
`Although Gil is generally silent with respect to redness reduction, using pain
`as an indicator of neurogenic inflammation, the ’742 Specification
`demonstrates that application of 0.03% brimonidine would also necessarily
`reduce redness when administered to patients with an ocular condition. See
`also Ex. 1025. We therefore conclude that Petitioner has established a
`reasonable likelihood of success in prevailing at trial with respect to at least
`one claim upon Ground 1.
`
`
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`4.
`
`Summary
`Having determined that Petitioner has established a reasonable
`likelihood of success in establishing at trial that claim 1 is unpatentable
`under 35 U.S.C. § 102 as anticipated by Gil (Ground I of the Petition), we
`consequently institute trial on claims 1–6 for all of the Grounds set forth in
`the Petition. See SAS Institute, Inc. v. Iancu, 138 S.Ct. 1348, 1354–55 (2018)
`(holding that, when inter partes review is instituted, the Board shall issue a
`final written decision with respect to the patentability of any patent claim
`challenged by the petitioner). We add below our comments on the remaining
`grounds for guidance to the parties.
`
`
`D. Ground II: Alleged Anticipation by Walters
`1. Overview of Walters (Ex. 1005)
`Walters is a presentation abstract published in the Annual Meeting
`Abstract Issue of Investigative Ophthalmology & Visual Science, and was
`publicly available at least on March 28, 1991. See Ex. 1005, 1. Walters is
`therefore prior art to the ’742 patent.
`Walters discloses administering 0.02% of a compound designated “AGN
`190342-LF” to patients with open-angle glaucoma or ocular hypertension.
`Ex. 1005. Walters does not identify “AGN 190342-LF” as brimonidine.
`Petitioner cites a number of exhibits that identify AGN 190342-LF as
`
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`brimonidine. See Pet. 37–39 (citing Ex. 10158; Ex. 10349; Ex. 102910; Ex.
`103011; Ex. 102812; Ex. 103113; Ex. 103514).
`
`
`2. Anticipation of Claims 1–2 by Walters: Petitioner’s contentions
`Petitioner argues that the disclosures of Walters anticipate each of the
`limitations of claims 1 and 2. Pet. 40–43.
`
`
`
`
`
`8 P. B. M. W. M. Timmermans, Structure-Activity Relationships in
`Clonidine-Like Imidazolidines and Related Compounds, 3(1) Prog.
`Pharmacol. 21–60 (1980) (“Timmermans”) (Ex. 1015).
`
` 9
`
` C. Du-Shieng et al., Corneal and Conjunctival/Scleral Penetration of p-
`aminoclonidine, AGN 190342, and Clonidine in Rabbit Eyes, 9(11)
`CURRENT EYE RES. 1051–059 (1990) (“Du-Shieng”) (Ex. 1034).
`
`
`10 R. David et al., Brimonidine in the Prevent
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