Trials@uspto.gov
`571-272-7822
`
`Paper 77
`Date: May 15, 2023
`
`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 TINA E. HULSE, ROBERT A. POLLOCK, and RYAN H. FLAX,
`Administrative Patent Judges.
`HULSE, Administrative Patent Judge.
`
`JUDGMENT
`Final Written Decision
`Determining All Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`
`
`
`
`
`571-272-7822
`
`Paper 77
`Date: May 15, 2023
`
`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 TINA E. HULSE, ROBERT A. POLLOCK, and RYAN H. FLAX,
`Administrative Patent Judges.
`HULSE, Administrative Patent Judge.
`
`JUDGMENT
`Final Written Decision
`Determining All Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`
`
`
`
`
`
`IPR2022-00142
`Patent 8,293,742 B2
`
`INTRODUCTION
`I.
`Slayback Pharma, LLC (“Petitioner”) 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”), owned by Eye Therapies, LLC (“Patent Owner”).
`Paper 2 (“Pet.”). Upon considering the Petition, Preliminary Response
`(Paper 7), Petitioner’s Reply to Patent Owner’s Preliminary Response
`(Paper 10), and Patent Owner’s Sur-Reply (Paper 12), on May 18, 2022, we
`instituted an inter partes review of the challenged claims of the ’742 patent.
`Paper 13 (“Dec. Inst.” or “Institution Decision”).
`Patent Owner then filed a Response to the Petition (Paper 30,
`“PO Resp.”), Petitioner filed a Reply (Paper 43, “Pet. Reply”), and Patent
`Owner filed a Sur-reply (Paper 59, “PO Sur-reply”).
`Petitioner also filed a Motion to Exclude Evidence (Paper 57), to
`which Patent Owner filed an Opposition (Paper 62), and Petitioner filed a
`Reply (Paper 64).
`An oral hearing was held on February 27, 2023. A portion of the
`hearing was closed so the parties could discuss confidential information filed
`under seal. A transcript of the public portion of the hearing has been entered
`in the record. Paper 75. A transcript of the closed portion of the hearing has
`been entered separately. Paper 74.
`After the hearing, the Board requested supplemental briefing on two
`issues: (1) whether the preamble of the claims should be construed as limited
`to a statement of the intentional purpose for which the method must be
`performed and, if so, what impact that construction has on inherent
`anticipation; and (2) what impact the transitional phrase “consisting
`essentially of” has on the claims and whether there is a temporal and intent
`aspect to the term. See Paper 69. Both parties submitted opening briefs
`
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`Patent 8,293,742 B2
`(Paper 70, “PO Supp. Br.”; Paper 71, “Pet. Supp. Br.”) and both parties
`submitted simultaneous responses to those briefs (Paper 73, “Pet. Reply
`Supp. Br.”; Paper 72, “PO Reply Supp. Br.”).
`We have authority under 35 U.S.C. § 6. We issue this Final Written
`Decision under 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. For the reasons
`that follow, we determine Petitioner has shown by a preponderance of the
`evidence that claims 1–6 of the ’742 patent are unpatentable.
`A. Real Parties-in-Interest
`Petitioner identifies itself, Slayback Pharma India LLP, Dr. Reddy’s
`Laboratories S.A., and Dr. Reddy’s Laboratories, Inc. as the real parties-in-
`interest. Paper 24, 1. Patent Owner identifies itself, Bausch & Lomb, Inc.,
`and Bausch & Lomb Ireland Limited as the real parties-in-interest. Paper 4,
`2.
`
`B. Related Proceedings
`Petitioner states that the ’742 patent has been asserted in the following
`cases: Bausch & Lomb, Inc. v. Slayback Pharma LLC, 3:21-cv-16766
`(D.N.J.); Bausch & Lomb, Inc. v. Lupin Ltd., 3:22-cv-00534 (D.N.J.).
`Paper 24, 1. Patent Owner states that the ’742 patent has also been asserted
`in Bausch & Lomb, Inc. v. Harrow Health, Inc., 3:21-cv-19252 (D.N.J.).
`Paper 4, 2.
`
`C. The ’742 Patent
`The ’742 patent is entitled “Preferential Vasoconstriction
`Compositions and Methods of Use.” Ex. 1001, code (54). The ’742 patent
`application was filed on July 27, 2009, and claims priority to a series of
`provisional applications, the earliest of which was filed on August 1, 2008.
`Id., codes (22), 60). Thus, the earliest possible effective filing date of the
`’742 patent claims is August 1, 2008. Pet. 14.
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`Patent 8,293,742 B2
`The ’742 patent relates to compositions and methods for preferential
`vasoconstriction of smaller blood vessels relative to larger blood vessels.
`Ex. 1001, Abstract. According to the Specification, dilation of small blood
`vessels causes undesirable events, including surface hemorrhage and
`hyperemia (i.e., eye redness) following Lasik surgery, eye redness, and nasal
`congestion. Id. at 1:6–11.
`Adrenergic receptors, which are divided into a-1 (or α-1 or alpha-1),
`a-2, and β-adrenergic receptor types, are involved in a variety of
`physiological functions, including functions of the cardiovascular and
`central nervous systems. Id. at 1:12–19. Agonists of a-2 adrenergic
`receptors are used in the treatment of hypertension, glaucoma, spasticity, and
`cancer pain. Id. at 1:25–29. Brimonidine is an example of a known
`compound having selective a-2 agonist activity. Id. at 1:48–49. According
`to the Specification, “[i]t is a known property of all a[lpha] adrenergic
`receptor agonists, including brimonidine, to cause vasoconstriction.” Id. at
`1:61–63. The Specification notes, however, that “known formulations of
`brimonidine and other known a-2 adrenergic receptor agonists are associated
`with a high incidence of rebound hyperemia,1 or other side effects, in
`clinical use.” Id. at 1:63–66.
`Moreover, the Specification states that commercially available general
`alpha agonists for topical ophthalmic use have high alpha-1 receptor agonist
`activity and are known to cause rebound hyperemia and medicamentosa (i.e.,
`a potentially prolonged inflammatory state that can last for several weeks or
`
`
`1 The ’742 patent states that “[r]ebound hyperemia refers to induced
`vasodilation (instead of intended vasoconstriction) occurring, often with a
`lag time, after an application or, more typically, repeated applications of
`vasoconstrictors.” Ex. 1001, 4:30–34.
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`Patent 8,293,742 B2
`months even after stopping the medication). Id. at 2:8–13, 26–28. Thus,
`clinical use of such a-1 receptor agonists are typically limited to several
`hours or days, even though users with more chronic conditions, like dry eye
`and allergic conjunctivitis, may require longer-term use. Id. at 2:14–21.
`The Specification explains that “there is a need for new methods and
`formulations that would provide safe and long term vasoconstriction with
`reduced or minimized side effects, such as rebound hyperemia.” Id. at 2:30–
`33.
`
`Accordingly, the Specification states that “[o]ne of the key discoveries
`of the present invention lies in using low doses of highly selective a-2
`adrenergic receptor agonists to achieve vasoconstriction with significantly
`reduced hyperemia.” Id. at 2:38–41.
`D. Illustrative Claim
`Petitioner challenges claims 1–6 of the ’742 patent. Claims 1 and 3
`are the only independent claims and are reproduced below.
`1. 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.
`3. A method for reducing eye redness consisting essentially
`of topically administering to a patient having an ocular
`condition a composition consisting essentially of brimonidine
`into ocular tissue, wherein pH of said composition is between
`about 5.5 and about 6.5, wherein said brimonidine
`concentration is between about 0.001% and about 0.025%
`weight by volume and wherein said composition is formulated
`as an ocular drop.
`Ex. 1001, 22:17–22, 26–32.
`
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`Patent 8,293,742 B2
`Claim 2 depends from claim 1 and further recites a concentration of
`brimonidine “between about 0.001% to about 0.025% weight by volume.”
`Id. at 22:23–25. Claim 4 depends from claim 3 and further recites topically
`administering the composition “within about 24 hours after a Lasik surgery
`on said patient.” Id. at 22:33–35. And claims 5 and 6 depend from claims 1
`and 3, respectively, and further recite that the ocular condition is “chronic
`red eye.” Id. at 22:36–39.
`E. The Asserted Grounds of Unpatentability
`Petitioner asserts that claims 1–6 of the ’742 patent are unpatentable
`on the following grounds:
`Claim(s) Challenged
`35 U.S.C. §2
`1–2
`102
`1–2
`102
`1–6
`103
`
`Reference(s)/Basis
`
`Gil3
`Walters4
`Gil, Norden5, Dean6,
`Alphagan7, and Federal
`Register8
`
`
`2 Because the claims at issue have an effective filing date before March 16,
`2013, the effective date of the applicable provisions of the Leahy Smith
`America Invents Act, Pub. L. No. 112–29, 125 Stat. 284 (2011) (“AIA”), we
`apply the pre-AIA versions of 35 U.S.C. §§ 102 and 103(a) in this Decision.
`3 Gil et al., US 6,294,553 B1, issued Sept. 25, 2001 (Ex. 1004, “Gil”).
`4 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 ASSOC.
`RES. VISION & OPHTHALMOL. 988 (1991) (Ex. 1005, “Walters”).
`5 R.A. Norden, Effect of Prophylactic Brimonidine or Bleeding
`Complications and Flap Adherence after Laser in Situ Keratomileusis. 18 J.
`REFRACTIVE SURG. 468–71 (2002) (Ex. 1006, “Norden”).
`6 Dean et al., US 6,242,442 B1, issued June 5, 2001 (Ex. 1007, “Dean”).
`7 ALPHAGAN® (brimonidine tartrate ophthalmic solution) 0.2%.
`Physicians’ Desk Reference, 52th ed., Medical Economics Company, Inc.,
`487 (1998) (Ex. 1008, “Alphagan”).
`8 53 Fed. Reg. 7076–7093 (Mar. 4, 1988) (Ex. 1009, “Federal Register”).
`
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`Patent 8,293,742 B2
`Petitioner relies upon the Declarations of Neal A. Sher, M.D., FACS
`(Exs. 1002 and 1049), Paul A. Laskar, Ph.D. (Exs. 1003 and 1048), and Ivan
`T. Hofmann (Ex. 1047). Patent Owner relies on the Declarations of Robert
`J. Noecker, MD, MBA (Ex. 2020), Robert O. Williams, III, Ph.D.
`(Ex. 2021), Stephen G. Davies, D. Phil. (Ex. 2022), John Ferris (Ex. 2023),
`and John C. Jarosz (Ex. 2024).
`II. ANALYSIS
`Petitioner bears the burden of proving unpatentability of the
`challenged claims, and that burden of persuasion never shifts to Patent
`Owner. Dynamic Drinkware, LLC v. Nat’l Graphics, Inc., 800 F.3d 1375,
`1378 (Fed. Cir. 2015). To prevail, Petitioner must prove unpatentability by
`a preponderance of the evidence.9 See 35 U.S.C. § 316(e); 37 C.F.R.
`§ 42.1(d) (2019).
`
`A. Person of Ordinary Skill in the Art
`In determining the level of ordinary 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).
`Petitioner contends that a person of ordinary skill in the art (“POSA”)
`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
`
`9 Although we find certain of Patent Owner’s arguments not persuasive, this
`should never be taken as an indication that we have assigned Patent Owner
`the burden of proof on patentability.
`
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`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 and 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).
`In our Institution Decision, we noted that Patent Owner did not
`contest Petitioner’s definition and adopted Petitioner’s definition as
`reasonable. Dec. Inst. 14. In its Response, Patent Owner states that a POSA
`“may be represented by a team of individuals with experience and various
`skills relating to eye care, including, inter alia, the medical and
`pharmaceutical arts.” PO Resp. 7. Patent Owner further asserts that a
`POSA would have had access to team members with experience in
`chemistry, designing and formulating ophthalmic formulations, and/or in
`administering such formulations to treat ocular conditions obtained by some
`combination of education and work experience. Id. at 7–8 (citing Ex. 2020
`¶ 29; Ex. 2021 ¶ 33; Ex. 2022 ¶ 19). Patent Owner notes that Petitioner’s
`definition of a formulator POSA goes beyond the level of a person of
`ordinary skill, and that a formulator POSA would have had a Bachelor’s
`degree in pharmaceutics or a related discipline with about three to five years
`of work experience in this area, or a comparable level of education and
`training, such as a Ph.D. with one or two years of experience in this area. Id.
`at 8 (citing Ex. 2020 ¶ 28; Ex. 2021 ¶ 32).
`Although the parties disagree as to the specific qualifications of a
`person of ordinary skill in the art, the parties’ experts agree that their
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`opinions would not change regardless of which definition is applied. See
`Ex. 1049 ¶ 6 (Sher); Ex. 2020 ¶ 28 (Noecker); Ex. 2021 ¶ 34 (Williams);
`Ex. 2022 ¶ 23 (Davies).
`Both parties’ proposed definitions and the prior art of record indicate
`a high level of skill in the relevant art. Because the parties’ respective
`experts agree that any dispute as to the level of ordinary skill in the art is not
`material to their opinions, we adopt Patent Owner’s definition as consistent
`with the prior art’s demonstration of the level of ordinary skill in the art at
`the time of the invention. See Ex. 2020 ¶¶ 28–31; see also 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))).
`
`B. Claim Construction
`In an inter partes review, 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). 37 C.F.R. § 100(b) (2021). 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
`
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`Patent 8,293,742 B2
`determining ‘the legally operative meaning of claim language.’” Phillips,
`415 F.3d at 1317.
`
`Preamble
`1.
`The claims of the ’742 patent each recite as their preamble “[a]
`method for reducing eye redness.” Ex. 1001, 22:17–39. Both parties agree
`that the preamble of the claims is limiting. PO Supp. Br. 3–6; Pet. Supp.
`Br. 2–3. The parties disagree, however, on what the preamble means.
`Petitioner asserts that the preamble “limits only [sic] the claims to the
`condition to be treated—eye redness.” Pet. Supp. Br. 3. Moreover,
`Petitioner asserts that there is no efficacy requirement in the claims, and, at
`most, the claims require that the composition be administered “with the
`intent to reduce redness.” Pet. Reply 7–8.
`Patent Owner disagrees, asserting that the preamble requires actual
`reduction in a patient’s ocular hyperemia. PO Supp. Br. 3.
`As an initial matter, we agree with the parties that the preamble of the
`claims is limiting. “Whether to treat a preamble as a claim limitation is
`determined on the facts of each case in light of the claim as a whole and the
`invention described in the patent.” Storage Tech. Corp. v. Cisco Sys., Inc.,
`329 F.3d 823, 831 (Fed. Cir. 2003). The Federal Circuit “has not hesitated
`to hold preambles limiting when they state an intended purpose for methods
`of using a compound.” Eli Lilly & Co. v. Teva Pharms. Int’l GmbH, 8 F.4th
`1331, 1342 (Fed. Cir. 2021). And where, as here, the claims are directed to
`methods of using a composition for a specific purpose (i.e., reducing eye
`redness), and the method comprises a single step of administering that
`composition, the Federal Circuit “has generally construed statements of
`intended purpose in such method claims as limiting.” Id. at 1340.
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`As for whether the preamble requires actual reduction in redness, we
`agree with Petitioner that it does not and find Eli Lilly to be instructive. In
`Eli Lilly, the preambles of the claims recite a “method for reducing incidence
`of or treating at least one vasomotor symptom in an individual” and a
`“method for treating headache in an individual.” 8 F.4th at 1335. There, the
`Federal Circuit held that the preambles “are not merely statements of effect
`but rather statements of the intentional purpose for which the methods must
`be performed.” Id. at 1342. Thus, the Federal Circuit did not require proof
`of actual clinical results from performing the claimed method, even though
`the claims also recited an “effective amount.” Id. The Federal Circuit held
`that because the specification defined an “effective amount” as an “an
`amount sufficient to effect beneficial or desired results” and provided
`examples of such results in the context of prophylactic or therapeutic uses,
`the claims “encompass a clinical result, [but] they do not require such a
`result.” Id.
`Here, similarly, the ’742 patent claims simply recite administering the
`brimonidine composition (at a concentration range) and do not recite any
`efficacy requirement, nor even the “effective amount” of note in the Eli Lilly
`claims. But, like Lilly and as explained below, the “ocular conditions” of the
`claims encompass prophylactic reduction of hemorrhage and hyperemia in
`addition to therapeutic uses. See Ex. 1001, 12:13–19. We, therefore, find
`the claims here do not require actual redness reduction and, thus, no clinical
`result is required to satisfy the claimed method.
`Thus, having considered the arguments and evidence presented at
`trial, we determine that the preamble of the claims is limiting and requires
`that the claimed brimonidine composition be administered with the
`
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`intentional purpose of reducing eye redness, whether or not eye redness is
`actually reduced.
`
`“consisting essentially of”
`2.
`Independent claims 1 and 3 recite the transition phrase “consisting
`essentially of.” Ex. 1001, 22:17–18, 25–26. That transition phrase has a
`distinct meaning in patent law and serves as a middle ground between
`closed-ended claims that use the phrase “consisting of” and open-ended
`claims that use the phrase “comprising.” AK Steel Corp. v. Sollac & Ugine,
`344 F.3d 1234, 1239 (Fed. Cir. 2003). As such, the use of “consisting
`essentially of” “signals that the invention necessarily includes the listed
`ingredients [but] is open to unlisted ingredients that do not materially affect
`the basic and novel properties of the invention.” PPG Indus. v. Guardian
`Indus. Corp., 156 F.3d 1351, 1354 (Fed. Cir. 1998). The Federal Circuit has
`instructed that determining the bounds of the basic and novel properties of
`an invention is a claim construction issue. HZNP Meds. LLC v. Actavis
`Labs. UT, Inc., 940 F.3d 680, 694–95 (Fed. Cir. 2019).
`Petitioner asserts that the allegedly novel aspect of the claimed
`invention is brimonidine’s ability to reduce eye redness at low doses, but
`does not exclude administration of other drugs. Pet. Supp. Br. 9–10 (citing
`Ex. 1001, 2:38–41 (stating “[o]ne of the key discoveries of the present
`invention lies in using low doses of [brimonidine] to achieve
`vasoconstriction with significantly reduced hyperemia”)). Patent Owner, on
`the other hand, argues that one of the basic and novel characteristics of the
`claimed methods is “administering brimonidine at the claimed
`concentrations as the sole drug.” PO Supp. Br. 11 (citing Ex. 1024, 115).
`Thus, the parties dispute whether the scope of the claims includes the use of
`additional drugs along with low-dose brimonidine.
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`Petitioner notes that the Specification states that “[o]ne of the key
`discoveries of the present invention lies in using low doses of [brimonidine]
`to achieve vasoconstriction with significantly reduced hyperemia.” Pet.
`Supp. Br. 10 (quoting Ex. 1001, 2:38–41). Petitioner also notes that the
`Specification does not exclude administration of other drugs with
`brimonidine, as evidenced by an entire section titled “Combination
`Treatments.” Id. (citing Ex. 1001, 15:35–16:43). Thus, in one embodiment,
`the Specification teaches a composition comprising a selective a-2
`adrenergic receptor agonist and a histamine antagonist. Id. (citing Ex. 1001,
`16:2–10).
`Patent Owner, on the other hand, relies heavily on the prosecution
`history of the ’742 patent. During prosecution, the claims recited “[a]
`method for inducing preferential vasoconstriction of smaller blood vessels
`relative to larger blood vessels comprising” administering a selective a-2
`adrenergic receptor agonist. Ex. 1024, 111. The examiner rejected the
`claims over Dean, which teaches administering brimonidine with
`brinzolamide to treat ocular diseases associated with compromised blood
`flow. PO Supp. Br. 11 (citing Ex. 1007, 2:22–29, 2:51–57, claim 2). To
`overcome the rejection, the patentee amended the claims to change the
`transitional phrase from “comprising” to “consisting essentially of” and
`noted that in Dean, “the administration of brimonidine alone is not sufficient
`to treat an ocular condition.” Id. at 11–12 (citing Ex. 1024, 116). The
`patentee explained that the claimed methods “do not include administering
`other active agents.” Id. (citing Ex. 1024, 124, 116–17, 120) (emphasis
`omitted). Patent Owner contends that the ’742 patent Specification’s
`teaching of embodiments that include other active drugs is not inconsistent
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`with its construction, because that is subject matter that is not claimed in the
`’742 patent. PO Reply Supp. Br. 8.
`We find Petitioner has the better position. We agree that the
`Specification sets forth the basic and novel property of the invention as a
`“key discover[y]” in the use of “low doses of [brimonidine] to achieve
`vasoconstriction with significantly reduced hyperemia.” Ex. 1001, 2:39–41.
`During prosecution, the patentee asserted that “[o]ne of the basic and novel
`characteristics of the presently claimed methods is that they do not require
`the use of any other active ingredients (emphasis added) in addition to
`brimonidine.” Ex. 1024, 115; see also id. at 144 (examiner stating same in
`Reasons for Allowance). But, unlike Patent Owner, we do not read the
`prosecution history as prohibiting the use of any other active ingredients
`besides brimonidine. To do so would construe the semi-open-ended
`transition phrase “consisting essentially of” to have the same scope as the
`closed transition phrase “consisting of.” AK Steel, 344 F.3d at 1239.
`Rather, under the proper scope of the claims and consistent with the
`prosecution history, the claimed methods cannot include additional active
`ingredients that are required to perform the method. Ex. 1024, 144 (stating
`in the Reasons for Allowance that the claimed methods “do not require the
`use of any other active ingredients in addition to brimonidine”) (emphasis
`omitted). As the patentee explained, “[t]he administration of brimonidine in
`the methods of Dean is a necessary but insufficient part of the taught
`methods; the other necessary part of the method is the administration of
`another active agent, i.e., brinzolamide.” Id. at 117 (emphasis added). In
`other words, the scope of the claims does not include additional active
`ingredients that are necessary to achieve “vasoconstriction with significantly
`reduced hyperemia.” See Ex. 1001, 2:39–41. Where brimonidine achieves
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`vasoconstriction with reduced hyperemia on its own, we find the “consisting
`essentially of” transition phrase does not preclude the use of additional
`active agents, even if those agents may also cause some degree of
`vasoconstriction.
`We find Ecolab, Inc. v. FMC Corp., 569 F.3d 1335 (Fed. Cir. 2009),
`to be instructive. There, the claims recited a method for sanitizing fowl
`using an aqueous peracetic acid (PAA) solution “which consists essentially
`of . . . peracetic acid.” Id. at 1342. The patentee argued that the transition
`phrase “consists essentially of” limited the claim scope to compositions
`containing PAA as the sole antimicrobial agent. Id. at 1343. The Federal
`Circuit disagreed, noting that the specification includes examples of
`compositions that contain agents other than PAA that are considered
`antimicrobial agents, even if they were not expressly identified as such. Id.;
`see also Kim v. Earthgrains Co., No. 01 C 3895, 2010 WL 625220, at *4
`(N.D. Ill. Feb. 18, 2010) (stating Ecolab “suggests that additional active
`ingredients which improve the performance of the basic claim formula, but
`do not otherwise change its function, do not materially alter the ‘basic and
`novel’ characteristics of the invention”), aff’d 451 F. App’x 922 (Fed. Cir.
`2011).
`Applying Ecolab here, because the Specification states that low-dose
`brimonidine alone can significantly reduce hyperemia, if there are additional
`agents beyond low-dose brimonidine administered to a patient that may also
`reduce eye redness (e.g., anti-inflammatory agents like steroids or pain
`medication), those additional agents would not materially affect the basic
`and novel characteristics of the invention.
`Thus, having considered the arguments and evidence presented at
`trial, we determine that the transitional phrase “consisting essentially of”
`
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`IPR2022-00142
`Patent 8,293,742 B2
`does not preclude the use of additional active agents that may also cause
`vasoconstriction and reduction of hyperemia along with low-dose
`brimonidine.
`
`“about 0.025%”
`3.
`Claims 2 and 3 of the ’742 patent recite brimonidine “at a
`concentration between about 0.001% to about 0.025% weight by volume.”
`Ex. 1001, 22:22–24, 29–30. Petitioner asserts that “about 0.025%” includes
`0.03% weight by volume (Pet. 31), whereas Patent Owner asserts that “about
`0.025%” means “0.025% plus or minus 10%” (PO Resp. 35). In our
`Institution Decision, we construed “about 0.025%” as including “0.03%.”
`Dec. Inst. 12. Having considered the parties’ respective arguments and
`evidence presented at trial, we maintain that Petitioner has the better
`position.
`“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 Techs., Inc. v. Waters Corp., 543 F.3d 1351, 1368 (Fed. Cir. 2008)
`(internal quotes omitted). To interpret the range in its technologic and
`stylistic context, we must consider how the term is used in the patent
`specification, the prosecution history, and other claims. Central Admixture
`Pharm. Svcs., Inc. v. Advanced Cardiac Solutions, P.C., 482 F.3d 1347,
`1355 (Fed. Cir. 2007). The range depends on what a person having ordinary
`skill in the art would reasonably consider “about” to encompass. See
`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
`[numerical limitation] to the invention.” Ortho-McNeil Pharm., Inc. v.
`
`16
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`IPR2022-00142
`Patent 8,293,742 B2
`Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1327 (Fed. Cir. 2007). As the
`Federal Circuit has explained, “it is the purpose of the limitation in the
`claimed invention—not the purpose of the invention itself—that is relevant.”
`Cohesive, 543 F.3d at 1368. “Extrinsic evidence of meaning and usage in
`the art may be helpful in determining the criticality of the parameter.”
`Ortho-McNeil, 476 F3d. at 1326 (quoting Pall Corp. v. Micron Separations,
`Inc., 66, F.3d 1211, 1217 (Fed. Cir. 1995)).
`Petitioner’s Contentions
`a)
`In reviewing the intrinsic evidence, Petitioner cites five disclosures of
`the ’742 patent that support its contention that “about 0.025%” includes
`“0.03%.” Pet. 28–30. First, Petitioner points to the Specification’s
`definition of “low concentrations” of brimonidine 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, 3:61–65; Ex. 1003 ¶ 65).
`Second, argues Petitioner, the Specification identifies concentration
`ranges up to about 0.05% brimonidine as “preferred” embodiments. Id.
`at 29 (citing Ex. 1001, 12:60–63, 14:14–16; 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
`selective a-2 adrenergic receptor agonist” is in a range up to “about
`0.035%.” Id. (citing Ex. 1001, 5:52–54, 9:14-16; 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 (citing
`Ex. 1001, 3:30-33, Fig. 4E). Petitioner also notes that the Specification
`
`17
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`IPR2022-00142
`Patent 8,293,742 B2
`states that the application of 0.033% brimonidine did not result in rebound
`hyperemia. Id. (citing Ex. 1001, 20:17–19; Ex. 1003 ¶ 69).
`Fourth, Petitioner notes that the Specification states 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, 2:2–8; 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).
`Finally, Petitioner cites extrinsic expert testimony 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 also
`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. (citing Ex. 1003 ¶ 72). Thus, Petitioner
`argues that for all these reasons, when properly construed, “about 0.025%”
`includes “0.03%” brimonidine. Id.
`
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`IPR2022-00142
`Patent 8,293,742 B2
`
`Patent Owner’s Contentions
`b)
`In response, Patent Owner argues that the ’742 patent separately
`discloses preferred concentrations of low-dose brimonidine, including
`“about 0.01%,” “ab
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