`Tel: 571-272-7822
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`Paper 12
`Date: August 6, 2020
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`AYLA PHARMA LLC,
`Petitioner,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`
`
`IPR2020-00295
`Patent 9,533,053 B2
`
`
`
`
`Before GRACE KARAFFA OBERMANN, CHRISTOPHER M. KAISER,
`and JAMIE T. WISZ, Administrative Patent Judges.
`
`KAISER, Administrative Patent Judge.
`
`
`
`
`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314
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`IPR2020-00295
`Patent 9,533,053 B2
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`INTRODUCTION
`
`A. Background
`Ayla Pharma LLC (“Petitioner”) filed a Petition (Paper 1, “Pet.”)
`requesting an inter partes review of claims 1–13 of U.S. Patent
`No. 9,533,053 B2 (Ex. 1002, “the ’053 patent”). Novartis AG (“Patent
`Owner”) filed a Preliminary Response.1 Paper 7 (“Prelim. Resp.”). With
`our authorization, Petitioner filed a Reply (Paper 10), and Patent Owner filed
`a Sur-Reply (Paper 11).
`We have authority to determine whether to institute an inter partes
`review. 35 U.S.C. § 314(b) (2018); 37 C.F.R. § 42.4(a) (2019). The
`standard for instituting an inter partes review is set forth in 35 U.S.C.
`§ 314(a), which provides that an inter partes review may not be instituted
`unless “there is a reasonable likelihood that the petitioner would prevail with
`respect to at least 1 of the claims challenged in the petition.”
`After considering the Petition, the Preliminary Response, the Reply,
`the Sur-Reply, and the evidence currently of record, we conclude that
`Petitioner has not shown a reasonable likelihood that it would prevail with
`respect to at least one challenged claim. Accordingly, we do not institute an
`inter partes review of the challenged claims on the grounds asserted in the
`Petition.
`
`
`1 Pursuant to the Notice of Waiver of Patent-Related Timing Deadlines
`under the Coronavirus Aid, Relief, and Economic Security Act issued
`March 31, 2020, Patent Owner requested, and we granted, a 30-day
`extension of the deadline for Patent Owner to file its Preliminary Response.
`Ex. 3001.
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`2
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`B. Related Matters
`The parties identify five lawsuits as related to this proceeding: Alcon
`Research, Ltd. v. Cipla Ltd., No. 1-17-cv-01244 (D. Del.); Alcon Research,
`Ltd. v. Lupin Ltd., No. 1-17-cv-00321 (D. Del.); Alcon Research, Ltd. v.
`Watson Labs. Inc., No. 1-17-cv-00252 (D. Del.); Alcon Research, Ltd. v.
`Watson Labs., Inc., No. 1:15-cv-1159 (D. Del.); and Alcon Research, Ltd. v.
`Lupin Ltd., No. 1:16-cv-00195 (D. Del.). Pet. 4; Paper 5, 2–3. In addition,
`the ’053 patent previously was challenged in IPR2018-01021, and a related
`patent, U.S. Patent No. 8,791,154 B2 (Ex. 1001, “the ’154 patent”),
`previously was challenged in IPR2016-00544, IPR2016-01640, and
`IPR2018-01020. Id.
`
`C. The Asserted Grounds of Unpatentability
`Petitioner contends that claims 1–13 of the ’053 patent are
`unpatentable based on the following grounds (Pet. 13–66):2
`Claim(s) Challenged
`35 U.S.C. §
`Reference(s)/Basis
`1–13
`103(a)
`Bhowmick,3 Yanni,4 and Castillo5
`
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`2 Petitioner also relies on a Declaration from S. Craig Dyar, Ph.D., adopting
`the earlier testimony of Paul A. Laskar, Ph.D. Ex. 1042 (adopting
`Ex. 1014).
`3 WO 2008/015695 A2, published Feb. 7, 2008 (Ex. 1003).
`4 J.M. Yanni et al., The In Vitro and In Vivo Ocular Pharmacology of
`Olopatadine (AL-4943A), an Effective Anti-Allergic/Antihistaminic Agent,
`12 J. OCULAR PHARMACOLOGY & THERAPEUTICS 389, 389–400 (1996)
`(Ex. 1004).
`5 US 6,995,186 B2, issued Feb. 7, 2006 (Ex. 1005).
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`3
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`Claim(s) Challenged
`1–13
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`1–13
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`35 U.S.C. §
`103(a)
`
`103(a)
`
`Reference(s)/Basis
`Schneider,6 Hayakawa,7
`Bhowmick, and Castillo
`Bhowmick, Schneider, and
`Castillo
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`D. The ’053 Patent
`The ’053 patent, titled “High Concentration Olopatadine Ophthalmic
`Composition,” issued on January 3, 2017. Ex. 1002, codes (45), (54).
`The ’053 patent “relates to an ophthalmic composition containing a
`relatively high concentration of olopatadine.” Id. at 1:17–19.
`According to the ’053 patent, symptoms of “allergic conjunctivitis,”
`including “ocular irritation [and] redness” are known to be “significantly
`reduced using topical ophthalmic solutions containing olopatadine.” Id. at
`1:28–35. Using higher concentrations of olopatadine in these topical
`ophthalmic solutions leads to “significantly improved reduction of late phase
`ocular allergic conjunctivitis symptoms” and “significantly improved
`reduction of redness in the early phase.” Id. at 1:36–46. Additionally, with
`these higher concentrations, symptom relief “can be achieved through once a
`day dosing” rather than only with “greater dosing frequencies.” Id. at 1:46–
`50. These benefits come at a cost, though: “[s]olubilizing high
`concentrations of olopatadine in a stable manner has proven difficult.” Id.
`at 2:3–4. The ’053 patent describes polyethylene glycol and
`polyvinylpyrrolidone as “hav[ing] proven incapable, alone or in
`combination, of solubilizing sufficient concentrations of olopatadine in
`
`
`6 US 2011/0082145 A1, published Apr. 7, 2011 (Ex. 1006).
`7 US 5,641,805, issued June 24, 1997 (Ex. 1007).
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`compositions having approximately neutral pH.” Id. at 2:10–18. In
`addition, although cyclodextrins “have the ability to solubilize significantly
`higher concentrations of olopatadine,” the “use of undesirably high
`concentrations of cyclodextrins has been found to reduce olopatadine
`efficacy and/or preservation efficacy of solutions.” Id. at 2:19–29.
`Accordingly, the invention of the ’053 patent “is directed at an ophthalmic
`composition that can provide high concentrations of olopatadine topically to
`the eye,” particularly “such a composition wherein the olopatadine is
`solubilized in solution in a stable manner, the composition exhibits
`consistent efficacy against late phase symptoms of allergic conjunctivitis,
`the composition exhibits sufficient antimicrobial activity to provide desired
`levels of preservation efficacy or any combination thereof.” Id. at 2:34–42.
`
`E. Illustrative Claims
`Claims 1–13 of the ’514 patent are challenged. Claims 1 and 8 are
`independent, and claim 1 is illustrative; it recites:
`1. An aqueous ophthalmic solution for treatment of
`ocular allergic conjunctivitis, the solution comprising:
`at least 0.67 w/v % olopatadine dissolved in the
`solution;
`PEG having a molecular weight of 200 to 800;
`polyvinylpyrrolidone;
`a cyclodextrin selected from the group consisting of
`SAE-β-cyclodextrin, hydroxypropyl-β-cyclodextrin
`and hydroxypropyl-γ-cyclodextrin; and
`water.
`Ex. 1002, 27:46–55.
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`ANALYSIS
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`A. Claim Construction
`In an inter partes review, we construe claim terms in an unexpired
`patent “in accordance with the ordinary and customary meaning of such
`claim as understood by one of ordinary skill in the art and the prosecution
`history pertaining to the patent,” as the claims would be construed “in a civil
`action under 35 U.S.C. 282(b).” 37 C.F.R. § 42.100(b) (2019). “[T]he
`ordinary and customary meaning of a claim term 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.” Phillips v. AWH Corp., 415 F.3d 1303, 1313 (Fed.
`Cir. 2005) (en banc). “Importantly, the person of ordinary skill in the art is
`deemed to read the claim term not only in the context of the particular claim
`in which the disputed term appears, but in the context of the entire patent,
`including the specification.” Id.
`Petitioner proposes construing “at least 0.67 w/v % olopatadine
`dissolved in the solution” as “at least encompass[ing] the district court’s
`construction.” Pet. 6–8. Patent Owner does not propose construing any
`terms. Prelim. Resp. 1–62. For the reasons discussed more fully below, we
`determine that we can decide whether to institute review without construing
`any terms. Accordingly, we do not decide any claim construction issues
`expressly. See Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co.,
`868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing 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.”)).
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`B. Obviousness over Bhowmick, Yanni, and Castillo
`Petitioner argues that claims 1–13 of the ’053 patent would have been
`obvious given the combined teachings of Bhowmick, Yanni, and Castillo.
`Pet. 13–38.
`
`1. Bhowmick
`Bhowmick relates to “an aqueous topical solution comprising a
`therapeutically effective amount of olopatadine.” Ex. 1003, code (57). It
`teaches that such solutions are “indicated for the treatment of signs and
`symptoms of allergic conjunctivitis.” Id. at 1:18–19. Bhowmick also
`teaches various compositions that “enhance the physical stability of” its
`olopatadine solutions, including cyclodextrin derivatives, such as “the
`hydroxypropyl derivatives of alpha-, beta-, and gamma-cyclodextrin” and
`“sulfoalkyl ether cyclodextrin.” Id. at 4:16–5:12. When discussing the use
`of hydroxypropyl-β-cyclodextrin to stabilize olopatadine solutions “for
`ophthalmic administration,” Bhowmick teaches using “about 1.0% to about
`5%” of the cyclodextrin derivative. Id. at 6:5–6. More broadly, Bhowmick
`teaches including between about 1.65 and about 50 times as much
`hydroxypropyl-β-cyclodextrin as olopatadine by weight. Id. at 6:18–20.
`Bhowmick teaches the use of other stabilizers, including hydroxypropyl
`methylcellulose in “concentrations ranging from about 0.001% to about
`5%.” Id. at 7:10–13. In addition, Bhowmick teaches adding other
`compounds, such as benzalkonium chloride as a preservative “in an amount
`ranging from about 0.005% to about 1%w/v,” and sodium borate as a
`buffering agent. Id. at 7:20–22, 8:14–21. Bhowmick teaches that its
`solution “is intended to be administered as . . . eye drops,” that its solution
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`has an osmolality “between 150 [and] 450 mOsm,” and that its solution “has
`a pH [of] 4 to 8, preferably pH of 6.5 to 7.5.” Id. at 8:10–12, 8:22–24.
`
`2. Yanni
`Yanni teaches that olopatadine “is an anti-allergic agent” and reports
`results of in vitro and in vivo studies of olopatadine using “human
`conjunctival mast cell preparations” as well as “guinea pigs.” Ex. 1004,
`389. Yanni teaches using solutions containing 0.001 to 1.0 w/v %
`olopatadine. Id. at 395.
`
`3. Castillo
`Castillo relates to “[t]opical formulations of olopatadine for treatment
`of allergic or inflammatory disorders of the eye.” Ex. 1005, code (57), 2:13–
`15. Castillo teaches aqueous solutions with 0.17 to 0.62 w/v % of
`olopatadine and “an amount of polyvinylpyrrolidone . . . sufficient to
`enhance the physical stability of the formulations.” Id. at code (57), 2:17–
`27, 2:66–3:2. The polyvinylpyrrolidone concentration in Castillo is taught
`as 0.1 to 3%. Id. at 3:22–25. Castillo also teaches the presence of other
`substances in the solutions, including polyols as tonicity-adjusting agents,
`benzalkonium chloride as a preservative, borates as buffering agents, and
`400-molecular-weight polyethylene glycol at a concentration of 2 w/v %.
`Id. at 3:64–67, 4:2–3, Table 5.
`
`4. Analysis
`Petitioner argues that claims 1–13 of the ’053 patent would have been
`obvious given the combined teachings of Bhowmick, Yanni, and Castillo.
`Pet. 13–38. “An invention is not obvious just ‘because all of the elements
`that comprise the invention were known in the prior art.’” Broadcom Corp.
`v. Emulex Corp., 732 F.3d 1325, 1335 (Fed. Cir. 2013) (quoting Power-One,
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`Inc. v. Artesyn Techs., Inc., 599 F.3d 1343, 1351 (Fed. Cir. 2010)). Instead,
`“a finding of obviousness at the time of invention requires a ‘plausible
`rational[e] as to why the prior art references would have worked together.’”
`Id. (quoting Power-One, 599 F.3d at 1352). We are not persuaded that
`Petitioner has shown sufficiently that a person of ordinary skill in the art
`would have had a reason to combine the teachings of Bhowmick, Yanni, and
`Castillo.
`Petitioner argues first that, “[i]n instituting on the challenged claims
`of the related ‘154 patent, the Board” found sufficient evidence of a reason
`to combine Bhowmick, Yanni, and Castillo, and “[s]imilar evidence exists
`here.” Pet. 17 (citing Ex. 1003, 7:20–22; Ex. 1005, 2:19–22; Ex. 1006 ¶ 7;
`Ex. 1014 ¶¶ 59, 60, 62–64, 70, 78, 79, 83, 90, 98, 119, 127, 136, 146, 149–
`151, 161, 180; Ex. 1015, 10, 25). This argument fails for two reasons.
`First, “mere statements . . . do not amount to a developed argument.”
`SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1320 (Fed. Cir.
`2006). Thus, the mere statement that evidence exists here that is “similar” to
`that which existed in an earlier proceeding fails to carry Petitioner’s burden
`to “set forth . . . [h]ow the construed claim is unpatentable” and to “state
`[the] relevance” of the evidence cited. 37 C.F.R. § 42.104(b)(4), (5). A
`proper argument would explain why the evidence shows that a person of
`ordinary skill in the art would have had a reason to combine the teachings of
`the references. Petitioner chooses instead to “ask [us] to play archaeologist
`with the record,” which we decline to do. DeSilva v. DiLeonardi, 181 F.3d
`865, 866–68 (7th Cir. 1999).
`Second, Petitioner’s reliance on the Board’s reasoning in IPR2016-
`00544 is the incorporation of an argument “by reference from one document
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`into another document,” which is prohibited by our rules. 37 C.F.R.
`§ 42.6(a)(3). Accordingly, we conclude that this argument is insufficient to
`demonstrate a reason to combine the teachings of Bhowmick, Yanni, and
`Castillo.
`Petitioner offers a second argument for combining the teachings of
`Bhowmick and Castillo: “A [person of ordinary skill in the art] would have
`been motivated to look to Castillo because, like Bhowmick, Castillo taught
`ophthalmic olopatadine solutions for treatment of allergic disorders
`comprising similar excipients.” Pet. 23. This argument also falls short.
`First, although this argument may be enough to show that the two references
`are analogous art, see Wyers v. Master Lock Co., 616 F.3d 1231, 1238 (Fed.
`Cir. 2010), simply demonstrating that a set of references are all directed to
`the same problem is not, by itself, a sufficient rationale to combine the
`references. See id. (upon finding that two references were directed to the
`same problem, proceeding to analyze whether a person of ordinary skill in
`the art would have been motivated to combine the references); see also In re
`Kahn, 441 F.3d 977, 987–88 (Fed. Cir. 2006) (inquiry as to whether a person
`of ordinary skill in the art would have sought to combine the references
`“picks up where the analogous art test leaves off”). Second, even if this
`argument were sufficient to show a reason to combine, it applies only to the
`combination of Castillo and Bhowmick, not to the combination of
`Bhowmick, Castillo, and Yanni on which Petitioner’s obviousness argument
`rests. Accordingly, we conclude that this argument also is insufficient to
`demonstrate a reason to combine the teachings of Bhowmick, Yanni, and
`Castillo.
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`Because neither of Petitioner’s arguments sufficiently shows a reason
`to combine the teachings of Bhowmick, Yanni, and Castillo, we conclude
`that Petitioner has not demonstrated a reasonable likelihood of prevailing in
`showing the obviousness of any challenged claim over this combination of
`references.
`
`C. Obviousness over Schneider, Hayakawa, Bhowmick, and Castillo
`Petitioner argues that claims 1–13 of the ’053 patent would have been
`obvious given the combined teachings of Schneider, Hayakawa, Bhowmick,
`and Castillo. Pet. 38–54.
`
`Schneider
`1.
`Schneider relates to “solution compositions comprising olopatadine.”
`Ex. 1006, code (57). In particular, Schneider “relates to formulations of
`olopatadine and their use for treating and/or preventing allergic or
`inflammatory disorders of the eye, nose, skin, and ear.” Id. It teaches that,
`“[i]n general, it is more desirable for active ingredients to be in solution
`rather than suspension in a pharmaceutical composition.” Id. ¶ 7.
`Schneider’s products are “pharmaceutical aqueous solution compositions,”
`id. ¶ 9, that “are used to treat . . . allergic conjunctivitis,” id. ¶ 48. The
`amount of olopatadine in Schneider is taught as “about . . . 0.60% w/v, or
`higher.” Id. ¶ 45. In addition to olopatadine, Schneider teaches adding
`several other compounds to its ophthalmic solutions, including sodium
`borate as a buffer, id. ¶ 44, water, id. ¶ 49, benzalkonium chloride as a
`preservative, id. ¶ 51, polyethylene glycol and polyvinylpyrrolidone “as
`lubricants or as viscosity agents,” id. ¶ 52, and dextrose, mannitol, sorbitol,
`propylene glycol, or glycerol as tonicity agents, id. ¶ 53. Schneider teaches
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`a composition pH between 6.0 and 7.5. Id. ¶ 44. It also teaches osmolality
`“about 150–450 mOsm, preferably 250–350 mOsm.” Id. ¶ 53.
`
`2. Hayakawa
`Hayakawa relates to “[t]opical ophthalmic formulations” containing
`olopatadine.8 Ex. 1007, code (57). Olopatadine is disclosed as having
`“human conjunctival mast cell stabilizing activity” and “significant
`antihistaminic activity.” Id. at 3:18–22. Accordingly, Hayakawa notes that
`olopatadine has both “a prophylactic effect” and “a therapeutic effect.” Id.
`at 3:22–23. Hayakawa discloses using olopatadine in concentrations ranging
`from “0.0001 to 5 w/v %,” id. at 6:43–44, with histamine inhibition
`increasing as the dose of olopatadine increases, id. at Table 1.
`
`3. Analysis
`Petitioner argues that claims 1–13 of the ’053 patent would have been
`obvious given the combined teachings of Schneider, Hayakawa, Bhowmick,
`and Castillo. Pet. 38–54.
`In arguing the obviousness of claims 1–13, Petitioner relies on the
`same arguments for reason to combine that we discussed above. Pet. 41–42
`
`
`8 Hayakawa uses “Compound A” or “11-(3-dimethylaminopropylidene)-
`6,11-dihydrodibenz[b,e]oxepin-2-acetic acid” to refer to either individual
`isomer or to a mixture of both isomers of 11-(3-dimethylaminopropylidene)-
`6,11-dihydrodibenz[b,e]oxepin-2-acetic acid. Ex. 1007, 3:10–15. This
`compound, in the hydrochloride salt of its Z isomer, is identified as
`olopatadine in Yanni. Ex. 1004, 389. Schneider identifies this compound,
`not in its hydrochloride salt, but still in its Z isomer, as olopatadine.
`Ex. 1006 ¶ 3. There is no evidence in the record contradicting the
`identification of the compound disclosed in Hayakawa as olopatadine.
`Accordingly, we use the term “olopatadine” when referring to the compound
`that Hayakawa discloses.
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`(arguing that we should find a reason to combine Schneider, Bhowmick,
`Castillo, and Hayakawa because “[s]imilar evidence [to that in IPR2016-
`00544] exists here”), 46 (arguing that a person of ordinary skill in the art
`would have combined Schneider and Castillo “because both references teach
`ophthalmic solutions for treatment of allergic disorders comprising
`olopatadine, reciting similar excipients”). As discussed above, however,
`neither of these arguments sufficiently shows a reason to combine the
`references. Accordingly, we conclude that Petitioner has not demonstrated a
`reasonable likelihood of prevailing in showing the obviousness of any
`challenged claim over the combination of Schneider, Hayakawa, Bhowmick,
`and Castillo.
`
`D. Obviousness over Bhowmick, Schneider, and Castillo
`Petitioner argues that claims 1–13 of the ’053 patent would have been
`obvious given the combined teachings of Bhowmick, Schneider, and
`Castillo. Pet. 54–66. With respect to a reason to combine the references,
`Petitioner argues that “the skilled artisan would have been motivated to
`combine the teachings of Schneider, Bhowmick and Castillo because they all
`teach olopatadine solutions for treatment of allergic disorders using similar
`excipients.” Id. at 54. As discussed above, this argument is insufficient to
`show a reason to combine because it speaks only to whether the teachings of
`the references could be combined, not why a person of ordinary skill in the
`art would have combined them. Accordingly, we conclude that Petitioner
`has not demonstrated a reasonable likelihood of prevailing in showing the
`obviousness of any challenged claim over the combination of Bhowmick,
`Schneider, and Castillo.
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`CONCLUSION
`Upon consideration of the Petition, the Preliminary Response, the
`Reply, the Sur-Reply, and the evidence presently before us, we determine
`that Petitioner has not shown a reasonable likelihood that it will prevail in
`showing that at least one of the challenged claims is unpatentable.
`Accordingly, we do not institute an inter partes review of any challenged
`claim based on any ground asserted in the Petition.
`
`
`ORDER
`
`It is hereby
`ORDERED that, pursuant to 35 U.S.C. § 314, the Petition is denied,
`and no inter partes review is instituted.
`
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`For PETITIONER:
`Jitendra Malik
`Alissa Pacchioli
`KATTEN MUCHIN ROSENMAN LLP
`jitty.malik@katten.com
`alissa.pacchioli@katten.com
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`
`For PATENT OWNER:
`Andrew Trask
`WILLIAMS & CONNOLLY LLP
`atrask@wc.com
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