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`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`
`SLAYBACK PHARMA LLC,
`
`Petitioner,
`
`v.
`
`EYE THERAPIES, LLC,
`
`Patent Owner.
`
`__________________
`
`Case IPR2022-00142
`U.S. Patent No. 8,293,742
`__________________
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`PATENT OWNER’S REPLY BRIEF ADDRESSING THE BOARD’S
`QUESTIONS
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`Case IPR2022-00142
`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`Table of Contents
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`b.
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`
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`Question 1: The Preamble and Inherent Anticipation ..................................... 1
`The preamble requires redness reduction .............................................. 1
`Even if the Preamble Only Requires an Intent to Reduce
`Redness, Petitioner Cannot Establish Anticipation ............................... 2
`a.
`The patient population in Example 1 of the ’553 patent
`does not mandate redness ......................................................... 3
`The steps of Example 1 of the ’553 patent are not
`identical to the claimed method ................................................ 5
`GlaxoSmithKline cannot save Petitioner’s position ................. 6
`c.
`Question 2: “Consisting Essentially of” .......................................................... 7
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`
`I.
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`II.
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`i
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`Case IPR2022-00142
`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`TABLE OF AUTHORITIES
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` Page(s)
`
`Cases
`Ecolab, Inc. v. FMC Corp.,
`569 F.3d 1335 (Fed. Cir. 2009) ............................................................................ 8
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`8 F.4th 1331 (Fed. Cir. 2021) ............................................................................... 1
`GlaxoSmithKline LLC v. Glenmark Pharms. Inc., USA,
`No. CV 14-877-LPS-CJB, 2017 WL 2290141 (D. Del. May 25,
`2017) ............................................................................................................. 3, 6, 7
`Jansen v. Rexall Sundown, Inc.,
`342 F.3d 1329 (Fed. Cir. 2003) ........................................................................ 1, 2
`Kingston Tech. Co. v. SPEX Techs., Inc.,
`798 F. App’x 629 (Fed. Cir. 2020) ..................................................................... 10
`Millennium Pharms., Inc. v. Sandoz Inc.,
`862 F.3d 1356 (Fed. Cir. 2017) ............................................................................ 4
`Mylan Pharms. Inc. v. Regeneron Pharms., Inc.,
`No. IPR2021-00881, 2022 WL 16842073 (P.T.A.B. Nov. 9, 2022) .................... 2
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) ............................................................................ 5
`Rapoport v. Dement,
`254 F.3d 1053 (Fed. Cir. 2001) ........................................................................ 6, 7
`Sanofi Mature IP v. Mylan Lab’ys Ltd.,
`757 F. App’x 988 (Fed. Cir. 2019) ................................................................... 1-2
`TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc.,
`529 F.3d 1364 (Fed. Cir. 2008) ............................................................................ 8
`Ventana Med. Sys., Inc. v. Biogenex Lab’ys, Inc.,
`473 F.3d 1173 (Fed. Cir. 2006) ............................................................................ 8
`
`ii
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`
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`I.
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`Case IPR2022-00142
`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`Question 1: The Preamble and Inherent Anticipation
` The preamble requires redness reduction
`There is no dispute that the preamble—a method for reducing eye redness—
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`is limiting. Instead, the parties dispute whether the preamble requires reduction of
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`ocular hyperemia as Patent Owner contends (Paper 71 at § II.A), or merely mens rea
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`regarding reducing redness without any effectiveness as Petitioner contends (Paper
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`70 at § I.A). Petitioner’s position is inconsistent with the claims themselves, intrinsic
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`record, and Federal Circuit precedent.
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`It is undisputed that the Federal Circuit’s decision in Eli Lilly & Co. v. Teva
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`Pharms. Int’l GmbH, 8 F.4th 1331 (Fed. Cir. 2021) is instructive. Paper 70 at 2-3.
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`The Federal Circuit’s guidance in Eli Lilly and Jansen v. Rexall Sundown, Inc., 342
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`F.3d 1329 (Fed. Cir. 2003) support construing the preamble to require redness
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`reduction. See Paper 71 at § II.A. Indeed, as in Eli Lilly and Jansen, the intrinsic
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`record of the ’742 patent emphasizes the essence of the invention—use of low dose
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`brimonidine to reduce redness. See e.g., EX-1001 at 2:38-41, 4:26-30. Moreover,
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`despite Petitioner’s suggestion to the contrary (Paper 70 at 2-3, n.1), the language in
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`the ’742 patent claims nearly parallels the language central to the court’s decision in
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`Jansen. Like Jansen where the claims recited “treating or preventing” a condition
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`“to a human in need thereof,” here, the claims recite “reducing eye redness” “to a
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`patient having an ocular condition.” 342 F.3d at 1332-34; see Sanofi Mature IP v.
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`1
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`Case IPR2022-00142
`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`Mylan Lab’ys Ltd., 757 F. App’x 988, 994 (Fed. Cir. 2019) (akin to Jansen, the
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`preamble “[a] method of increasing survival” requires increasing survival).
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`Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR2021-00881, 2022
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`WL 16842073 (P.T.A.B. Nov. 9, 2022) is inapposite. The Board’s conclusion in
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`Mylan turned on facts not present here. See id. at *9. For context, the claims in Mylan
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`were directed to a sequential dosage regimen (i.e., timing of doses), where it was
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`undisputed that the method of using the compounds at issue (VEGF antagonists) for
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`the claimed use (treating angiogenic eye disorders) was known. Id. at *3. The claims
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`did not recite any concentrations of the VEGF antagonists, but rather focused only
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`on timing of dosing. Id. at *9. Additionally, the preamble recited “treating a patient
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`with an angiogenic eye disorder,” akin to administering the compound, without
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`requiring (or even describing) a specific result in the claims. Id. The facts here are
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`materially different from those in Mylan. As an example, there is no such concession
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`about the method of use being known in the art. In fact, the inventors surprisingly
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`discovered that low-dose brimonidine could work to reduce redness, and therefore
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`claimed use of specific doses of brimonidine—“between about 0.001% . . . and
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`about 0.05%” and “between about 0.001% to about 0.025%”—for reducing eye
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`redness. EX-1001 at claims 1-3. Because the facts and claim language central to the
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`decision in Mylan are not present here, Petitioner’s reliance on this case is misplaced.
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`
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`Even if the Preamble Only Requires an Intent to Reduce
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`2
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`Case IPR2022-00142
`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`Redness, Petitioner Cannot Establish Anticipation
`Petitioner fails to address the implications of the Board adopting Patent
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`Owner’s construction and finding that the preamble requires redness reduction, not
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`merely intent. The reason for that is clear. Petitioner has not and cannot prove
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`inherency if redness reduction is required. Petitioner effectively conceded as much
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`when it shifted its position in its reply to argue that the claims require only intent to
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`reduce redness. Compare e.g., Paper 2 at § IV.A.2.a with Paper 43 at 7-8.
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`Importantly, even if the Board adopts Petitioner’s construction, Petitioner still
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`cannot meet its burden. See, e.g., Paper 71 at § II.B. Petitioner’s inherency argument
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`hinges on the Board finding that both the physical steps and patient population in
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`Example 1 of the ’553 patent are identical to the claimed method. See Paper 70 at
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`§ I.B (citing GlaxoSmithKline LLC v. Glenmark Pharms. Inc., USA, No. CV 14-877-
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`LPS-CJB, 2017 WL 2290141 (D. Del. May 25, 2017)). Neither the patient
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`population nor physical steps are the same.
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`a.
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`The patient population in Example 1 of the ’553
`patent does not mandate redness
`With respect to the patient population, Petitioner must establish that the
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`patients after radial keratotomy (“RK”) surgery (the population in Example 1) would
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`necessarily have eye redness to prove inherent anticipation. Petitioner relies entirely
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`on the testimony of Dr. Sher on this point. Paper 43 at 8; Paper 70 at 6. But what
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`3
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`Petitioner conveniently fails to mention is that Dr. Sher has never performed the
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`RK surgery in Example 1. See EX-2213 at 12:25-13:7 (“Q: Have you done RK
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`surgery other than the astigmatic RK surgery that you mentioned just a moment ago?
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`A: No. I don’t believe in it. . . .”). Because Dr. Sher has not performed RK surgery,
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`his unsupported testimony that all RK patients would have redness should be
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`rejected. See Millennium Pharms., Inc. v. Sandoz Inc., 862 F.3d 1356, 1365 (Fed.
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`Cir. 2017) (reversing a finding of invalidity where, inter alia, the petitioner’s expert
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`had “never worked with any boronic acid compound and has not performed or
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`supervised any lyophilization experiments since 1983.”)
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`Petitioner contends that Dr. Sher’s testimony is “unrebutted.” Paper 70 at 13.
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`That is incorrect. Patent Owner’s expert Dr. Noecker, the only expert in this case
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`who actually has performed RK surgery (EX-1053 at 95:1-3 (“Q: In your -- have
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`you ever performed radial keratotomy? A: Yes.”)), also addressed this issue. And
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`Dr. Noecker explained, from his own experience, redness does not always (i.e.,
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`necessarily and inevitably) result from radial keratotomy surgery.1 See, e.g., EX-
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`2020, ¶¶ 105, 149. This is logical, for it is important to realize that RK surgery
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`1 Tellingly, Petitioner’s counsel did not ask about Dr. Noecker’s patient outcomes
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`with respect to redness. This makes sense, because he had already given his position
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`in writing. See, e.g., EX-2020, ¶¶ 105, 149.
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`4
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`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`involves making microscopic cuts in the cornea, which is avascular—meaning there
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`are no blood vessels, as Dr. Sher acknowledged. EX-2162 at 113:12-17; EX-2020,
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`¶¶ 35, 104. Thus, unlike vascular parts of the body (including vascular parts of the
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`eye), where cuts result in blood (and redness (see EX-2020 at ¶ 38)), the situation in
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`the avascular cornea is different. Dr. Noecker’s clinical experience is thus
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`unsurprising and consistent with logic and science.2
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`Because Petitioner cannot establish that all of the patients in Example 1 of the
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`’553 patent would have had redness to reduce, its inherency argument must fail. See
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`Perricone v. Medicis Pharm. Corp., 432 F.3d 1368, 1376-79 (Fed. Cir. 2005) (if
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`providing the claimed treatment may have different results based upon the specific
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`patient (with or without sunburn) treated, the results are not inherent).3
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`b.
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`The steps of Example 1 of the ’553 patent are not
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`2 Dr. Sher’s testimony to the contrary was likely based on his experience with
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`astigmatism keratotomy, a different procedure (EX-2213 at 12:20-24), performed on
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`the edge of the cornea closer to the vascular part of the eye (EX-2020 at ¶¶ 33, 38).
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`3 Patent Owner and Petitioner both cite to Perricone, but Petitioner tellingly fails to
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`address the Court’s ultimate finding in Perricone that the claims were not anticipated
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`because the method in the prior art was not identical to the claimed methods because
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`of differences in the patient population. 432 F.3d at 1376-79
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`5
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`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`identical to the claimed method
`Petitioner additionally has not and cannot prove that the steps of Example 1
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`of the ’553 patent are identical to the steps in the claimed methods. The reason for
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`this is simple: Example 1 is incomplete as written and a POSA would have
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`recognized that other drugs would be ocularly administered, as Dr. Sher
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`acknowledged. EX-2213 at 18:10-23:13. Performing the method of Example 1 of
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`the ’553 patent thus includes steps involving administration of other drugs whereas
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`the claimed methods exclude steps involving administration of drugs other than
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`brimonidine. See, e.g., Paper 71 at §§ II.B, III. The methods thus are not identical,
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`and Petitioner’s inherent anticipation argument must fail for this additional reason.
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`GlaxoSmithKline cannot save Petitioner’s position
`c.
`Petitioner argues that this case is square with GlaxoSmithKline, but
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`GlaxoSmithKline is inapposite and involved what amounts to an opposite factual
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`situation. In GlaxoSmithKline, the court explained that a patentee may not
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`circumvent inherency by adding an intent limitation to claims. 2017 WL 2290141,
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`at *2. Here, it is Petitioner, not Patent Owner, who now attempts to insert an “intent”
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`element to circumvent the language of the claims (which require “redness
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`reduction”) and resurrect its maligned inherency position. The District of Delaware
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`in GlaxoSmithKline, moreover, cited Rapoport v. Dement, 254 F.3d 1053 (Fed. Cir.
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`2001), which found no inherency, “where intent for administering buspirone as part
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`6
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`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`of asserted claims—to treat sleep apnea—resulted in manipulative difference from
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`method disclosed in prior art—which was to treat anxiety; dosing regime for anxiety
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`was three times daily while regime for sleep apnea was larger dose once a day at
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`time of sleep.” GlaxoSmithKline, 2017 WL 2290141, at *2. Here, even if the Board
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`finds that the claims merely require “intent” as opposed to actual redness reduction,
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`Petitioner’s inherency position still fails because, similar to Rapoport, the claimed
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`methods and Example 1 of the ’553 patent have manipulative differences beyond
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`just the intent to treat pain versus the intent to treat redness. Namely, the dosing
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`protocol and dose (about 0.025% brimonidine without other drugs (e.g., claim 2)
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`versus 0.03% brimonidine with other drugs) are different and these differences
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`impact the patient population, i.e., whether the patients even have eye redness to
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`reduce and if 0.03% brimonidine alone would inevitably reduce redness if present.
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`II. Question 2: “Consisting Essentially of”
`The parties agree that “consisting essentially of” excludes steps that materially
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`affect the basic and novel characteristics of the claimed invention. See Paper 70 at
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`8-9; Paper 71 at 10. The parties dispute, however, what the basic and novel
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`characteristic of the invention is and what steps would materially affect it.
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`Petitioner contends that the basic and novel characteristic of the invention is
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`“brimonidine’s ability to reduce eye redness at low doses,” which “does not exclude
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`administration of other drugs.” Paper 70 at 9-10. But in making this argument,
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`7
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`Petitioner ignores key aspects of the prosecution history. See id. The “consisting
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`essentially of” phrase was added during prosecution to overcome Dean, EX-1007,
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`which administered brinzolamide (not a vasoconstrictor) with brimonidine. In
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`replacing “comprising” with “consisting essentially of” (EX-1024 at 111), the
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`patentee made it clear that the claimed methods “do not include administering other
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`active agents” with low-dose brimonidine (Id. at 124, 116-117, 120).
`
`Petitioner argues that Patent Owner’s position regarding administration of
`
`other drugs “cannot be squared with the ’742 patent itself.” See Paper 70 at 9-10, 13-
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`14. But as is often the case, the ’742 patent’s specification contains subject matter
`
`that is not claimed, and claims need not be construed to encompass all disclosed
`
`embodiments, particularly when narrowed during prosecution. See TIP Sys., LLC v.
`
`Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1373 (Fed. Cir. 2008) (declining
`
`“to construe the claim term to encompass the alternative embodiment” where doing
`
`so “would contradict the language of the claims”); see also Ventana Med. Sys., Inc.
`
`v. Biogenex Lab’ys, Inc., 473 F.3d 1173, 1181 (Fed. Cir. 2006). Notably, this patent
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`family contains other patents with different claims that use the “comprising”
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`transitional term (see, e.g., Slayback Pharma LLC v. Eye Therapies, LLC, IPR2022-
`
`00146, EX-1001 at claims 1, 3, 5) and cover co-administration with other drugs. As
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`such, Ecolab, Inc. v. FMC Corp., 569 F.3d 1335 (Fed. Cir. 2009) is inapposite.
`
`Petitioner also cites claim 4, directed to administering brimonidine “within
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`8
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`Case IPR2022-00142
`Patent Owner’s Reply Brief Addressing the Board’s Questions
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`about 24 hours after a Lasik surgery,” to argue the claims include dosing with other
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`drugs. See Paper 70 at 15. That is a red herring, for claim 4 is controlled and limited
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`by “consisting essentially of” and what the patentee argued it included (brimonidine
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`alone) and excluded (other drugs) during prosecution. Yet claim 4 still has scope. It
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`includes dosing with brimonidine alone in the claimed timeframe (within about 24
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`hours of surgery), and the postoperative use of other drugs (e.g., steroids or NSAIDs)
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`may only extend a few hours post-surgery, leaving ample room for brimonidine
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`alone to be administered well after those drugs wear off. Petitioner cites to EX-2213
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`at 23:11-13, but this testimony explains only that during surgery an anesthetic would
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`be given, providing no information on what happens postoperatively at, e.g., 24
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`hours. And although the record is undeveloped on this new argument, the reality is
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`that not all patients require other active ingredient drops post-surgery. See e.g., EX-
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`1102 and EX-1104 (describing no post-operative medication).
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`Conceding that other drugs would be administered if a POSA were to practice
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`Example 1 of the ’553 patent, Petitioner now must argue that those other drugs do
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`not impact brimonidine’s ability to reduce redness. Paper 70 at § II.B. But that
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`cannot be reconciled with Dr. Sher’s clear admission that steroids could be
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`administered as part of RK surgery and would reduce redness, thus impacting
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`brimonidine’s ability to do so. EX-2213 at 18:23-19:25. The same is true for
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`NSAIDs and antibiotics, which, despite Petitioner’s suggestion, is not speculative
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`9
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`given Dr. Sher’s testimony clearly admitting that anti-inflammatories and antibiotics
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`are administered and they would impact redness. Id. at 18:10-21:8.
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`In an attempt to salvage its inherency argument, Petitioner asserts yet another
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`new, speculative argument. This time, Petitioner argues the ’553 patent and Norden
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`were designed with “controls,” and the results show that the other drugs
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`administered do not impact brimonidine’s ability to reduce redness. See Paper 70 at
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`12-13. But these drugs not only would potentially prevent the formation of redness
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`in the first instance, but they also might reduce redness or cause some other
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`synergistic (or dys-synergistic) effect. EX-2213 at 18:23-21:8, 41:21-42:4.
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`Additionally, Petitioner ignores that Norden administered 0.2% brimonidine, a
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`concentration well above the claimed ranges and known to cause hyperemia rather
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`than reducing it. See, e.g., Paper 30 at §§ VI.C.1.d.ii; Paper 59 at § III.C.1.a.i.
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`Petitioner’s endless position shifting establishes only one thing: There are a
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`multitude of unknowns in its references. With this untenable foundation, Petitioner
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`cannot satisfy its heavy burden of proving inherent anticipation. Kingston Tech. Co.
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`v. SPEX Techs., Inc., 798 F. App’x 629, 634 (Fed. Cir. 2020) (affirming no inherent
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`anticipation on theory that relied on multiple inferential steps).
`
`Date: March 27, 2023
`
`Respectfully submitted,
`
`
`
`By: /Bryan C. Diner/
`Bryan C. Diner, Reg. No. 32,409
`Justin J. Hasford, Reg. No. 62,180
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`10
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`Case IPR2022-00142
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`Caitlin E. O’Connell, Reg. No. 73,934
`Christina Ji-Hye Yang, Reg. No. 79,103
`
`Finnegan, Henderson, Farabow,
` Garrett & Dunner, LLP
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`11
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`CERTIFICATE OF SERVICE
`
`The undersigned certifies that a copy of the foregoing Patent Owner’s Reply
`
`
`
`Brief Addressing the Board’s Questions was served electronically via email on
`
`March 27, 2023, in its entirety on the following:
`
`Linnea P. Cipriano
`Goodwin Proctor LLP
`620 Eight Avenue
`New York, NY 10018
`lcipriano@goodwinlaw.com
`
`Louis H. Weinstein
`Patrick G. Pollard
`Windels Marx Lane & Mittendorf, LLC
`1 Giralda Farms
`Madison, NJ 07940
`lweinstein@windelsmarx.com
`ppollard@windelsmarx.com
`
`Robert Frederickson III
`Goodwin Proctor LLP
`100 Northern Avenue
`Boston, MA 02210
`rfrederickson@goodwinlaw.com
`
`Petitioner has consented to service by electronic mail.
`
`
`
`
`
`
`
`
`
` /Geneva Eaddy/
`Geneva Eaddy
`Case Manager
`FINNEGAN, HENDERSON, FARABOW,
` GARRETT & DUNNER LLP
`
`Dated: March 27, 2023
`
`
`
`
`
`
`
`
`
`
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