Case IPR2022-00142
`U.S. Patent No. 8,293,742
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SLAYBACK PHARMA LLC
`
`Petitioner
`
`v.
`
`EYE THERAPIES LLC
`
`Patent Owner
`
`
`Case No. IPR2022-00142
`U.S. Patent No. 8,293,742
`
`
`PETITIONER’S REPLY
`
`
`U.S. Patent No. 8,293,742
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SLAYBACK PHARMA LLC
`
`Petitioner
`
`v.
`
`EYE THERAPIES LLC
`
`Patent Owner
`
`
`Case No. IPR2022-00142
`U.S. Patent No. 8,293,742
`
`
`PETITIONER’S REPLY
`
`
`
`TABLE OF CONTENTS
`
`
`I.
`II.
`
`INTRODUCTION ........................................................................................... 1
`CLAIM CONSTRUCTION ............................................................................ 1
`A. Ocular Condition ................................................................................... 1
`B.
`“About 0.025%” .................................................................................... 2
`III. THE ’553 PATENT ANTICIPATES CLAIMS 1 AND 2 .............................. 7
`IV. THE CHALLENGED CLAIMS ARE OBVIOUS ......................................... 9
`A.
`The Prior Art Taught Toward Brimonidine, Not Away ...................... 10
`B. A POSA Would Not Have Understood Brimonidine’s Ability to
`Reduce Redness to Be Concentration Dependent ............................... 15
`POSA Would Have Been Motivated to Use pH Within the Claimed
`Range ................................................................................................... 17
`1.
`There Was No Recognized “Progression” Toward Higher pH 18
`2.
`Eye Redness Relievers Work on the Surface of the Eye .......... 19
`3.
`There Is a Range of pH That Is Tolerable to Patients ............... 20
`D. A POSA Would Have Been Able to Make the Claimed Formulations
`With Routine Skill ............................................................................... 21
`Claims 4-6 Are Also Obvious ............................................................. 22
`Secondary Considerations Are Insufficient to Overcome an
`Obviousness Finding ........................................................................... 22
`
`C.
`
`E.
`F.
`
`
`
`
`
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`
`
`Case IPR2022-00142
`U.S. Patent No. 8,293,742
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`ABT Sys., LLC v. Emerson Elec. Co.,
`797 F.3d 1350 (Fed. Cir. 2015) .......................................................................... 24
`Amgen Inc. v. Hoeschst Marion Roussel, Inc.,
`314 F.3d 1313 (Fed. Cir. 2003) ...................................................................... 9, 11
`Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc.,
`752 F.3d 967 (Fed. Cir. 2014) ............................................................................ 24
`C.R. Bard, Inc. v. Medline Indus., Inc.,
`No. 2020-1900, 2021 WL 3574043 (Fed. Cir. Aug. 13, 2021) .................... 12, 13
`Ethicon Endo-Surgery, Inc. v. Covidien LP,
`812 F.3d 1023 (Fed. Cir. 2016) .................................................................... 25, 26
`Fox Factory, Inc. v. SRAM, LLC,
`944 F.3d 1366 (Fed. Cir. 2019) .......................................................................... 23
`In re Fulton,
`391 F.3d 1195 (Fed. Cir. 2004) .......................................................................... 17
`Hill-Rom Serv., Inc. v. Stryker Corp.,
`755 F.3d 1367 (Fed. Cir. 2014) ............................................................................ 2
`Micron Tech., Inc. v. Lone Star Silicon Innovations LLC,
`IPR2017-01562, 2018 WL 6602102 (P.T.A.B. Dec. 13, 2018) ........................... 3
`Microsoft Corp. v. Mira Advanced Tech., Inc.,
`IPR2017-01411, 2018 WL 6204170 (P.T.A.B. Nov. 27, 2018) ........................... 3
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) .......................................................................... 23
`Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Lab’ys,
`476 F.3d 1321 (Fed. Cir. 2007) ............................................................................ 4
`Par Pharm., Inc. v. Hospira, Inc.,
`835 F. App’x 578 (Fed. Cir. 2020) ....................................................................... 4
`
`
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`
`
`Case IPR2022-00142
`U.S. Patent No. 8,293,742
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .................................................................... 17, 24
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) .......................................................................... 22
`Schering Corp v. Geneva Pharms.,
`339 F.3d 1373 (Fed. Cir. 2003) ........................................................................ 8, 9
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996) .............................................................................. 6
`
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`EXHIBIT LIST
`
`Exhibit
`
`Description
`U:S. Patent No. 8,293,742 (filed July 27, 2009) (issued Oct. 23, 2012)
`
`(°742 Patent)
`
`1002
`Expert Declaration of Neal A. Sher, M.D. (Sher)
`aS. PatentNo. 6,294,553eeeFeb. 14, 2001)(issuedSep. 25,2001)
`
`
`
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`
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`
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`pear%20reddish%20or%20pink (last accessed Dec. 14, 2022) (Mayo
`Clinic 2022)
`Subconjunctival hemorrhage - American Academy of Ophthalmology,
`https://www.aao.org/image/subconjunctival-hemorrhage-7 (last accessed
`December 14, 2022)
`Chapter 43: Ophthalmic Solutions of Remington: The Science and Practice
`of Pharmacy (2000)
`Aslanides I.M., et al., Letter to the Editor. Ophthalmology Volume 112,
`Number 12, December 2005. 2238.e8-2238.e9 (Aslanides 2005)
`Aslanides I.M., et al., The Effect of Topical Apraclonidine on
`Subconjunctival Hemorrhage and Flap Adherence in LASIK Patients.
`Journal of Refractive Surgery, Volume 22, June 2006. 585-588
`Hong, S., et al., Effect of Prophylactic Brimonidine Instillation on
`Bleeding During Strabismus Surgery in Adults. American Journal of
`Ophthalmology. Volume 144, Issue 3, pp. 469-470, September 2007
`(Hong 2007)
`
`1103
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`1104
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`
`
`I. INTRODUCTION
`As set forth in the Petition, the challenged claims are either anticipated or
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`rendered obvious in light of the prior art. Patent Owner’s Response seeks to
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`obscure the relevant issues and ignores key aspects of the prior art. In all, Patent
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`Owner’s arguments are insufficient to overcome a finding that the challenged
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`claims are invalid.
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`II. CLAIM CONSTRUCTION
`Patent Owner disputes the construction of two terms in the challenged
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`claims. In both instances, Patent Owner’s arguments unduly narrow the claims and
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`should be rejected.
`
`A. Ocular Condition
`Patent Owner contends that “ocular condition” should be limited to “a
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`condition of the eye causing ocular hyperemia,” but does not point to anything in
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`the specification to support that interpretation. Paper-30, p.25. The ’742 patent
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`provides a broad, non-limiting list of ocular conditions for which the claimed
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`invention can be used. EX-1001, 12:13-13:10. This list includes examples of both
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`redness and hemorrhage that occur after ocular surgeries, and conditions that are
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`not known to cause hyperemia. EX-1001, 12:15-19; EX-1049, ¶36. Patent
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`Owner’s claim construction would improperly create a definition for “ocular
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`condition” in the claims that is narrower than the explicit definition in the
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`specification. Patent Owner’s argument is specifically aimed at establishing that
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`Case IPR2022-00142
`U.S. Patent No. 8,293,742
`radial keratotomy is not an “ocular condition,” but as Dr. Sher explains, there is no
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`basis for this exclusion, particularly since Patent Owner does not dispute that
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`LASIK is an ocular condition of the claims. EX-1049, ¶¶45-48. Therefore, Patent
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`Owner’s arguments attempting to carve out problematic aspects of the prior art
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`should be rejected.
`
`B.
`“About 0.025%”
`The Board should reject Patent Owner’s attempt to construe “about 0.025%”
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`to exclude 0.03%. As Patent Owner acknowledges, “the term ‘about’ should be
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`given its ordinary and accepted meaning of ‘approximately,’ absent patentee acting
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`as his own lexicographer.” Paper-30, pp.27-28 (citing Merck & Co. v. Teva
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`Pharms. USA, Inc., 395 F.3d 1364, 1370-72 (Fed. Cir. 2005)). Patent Owner is
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`wrong, however, that the patentee here was its own lexicographer. Id., p.30. The
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`standing for lexicography is “exacting.” Hill-Rom Servs., Inc. v. Stryker Corp.,
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`755 F.3d 1367, 1371 (Fed. Cir. 2014). “To act as its own lexicographer, a patentee
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`must clearly set forth a definition of the disputed claim term” and must “clearly
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`express an intent to redefine the term.” Id. Although express definitions for other
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`terms appear under the heading “Definitions,” there is no definition of “about” or
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`“about 0.025%.” See EX-1001, 3:55-4:24.
`
`The crux of Patent Owner’s argument is that the ’742 patent separately
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`refers to “about 0.025%” and “about 0.03%” in “two successive paragraphs.”
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`2
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`U.S. Patent No. 8,293,742
`Paper-30, p.29. At the outset, the mere use of these terms in the specification is
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`not lexicography. See Micron Tech., Inc. v. Lone Star Silicon Innovations LLC,
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`IPR2017-01562, 2018 WL 6602102, *4-*5 (P.T.A.B. Dec. 13, 2018) (finding
`
`individual embodiments do not amount to lexicography). Notably, the “two
`
`successive paragraphs” referred to in the specification have nothing to do with
`
`reducing eye redness, and Patent Owner offers no explanation for why the cited
`
`embodiments change the commonly used meaning of “about.”1 EX-1001, 8:46-55;
`
`8:56-63.
`
`Patent Owner’s claim that the patentee acted as a lexicographer is
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`particularly untenable in view of its separate argument—based entirely on extrinsic
`
`evidence—that “about” should mean ±10%. Paper-30, pp.35-36. Patent Owner
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`relies on “typical” FDA acceptance criteria and a notation in the U.S.P. for this
`
`definition (id.), but cannot point to anything in the ’742 patent that adopts the
`
`numerical limitations of this extrinsic evidence. See Microsoft Corp. v. Mira
`
`
`1 Patent Owner’s logic is also flawed. Even if the patentee intended “about
`
`0.025%” and “about 0.03%” to have separate meanings, the two ranges could still
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`overlap and “about 0.025%” could still capture a brimonidine concentration of
`
`0.03%. EX-1048, ¶¶14-15 (illustrating that Patent Owner’s alternative
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`construction of “about” also results in overlapping ranges).
`
`
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`3
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`U.S. Patent No. 8,293,742
`Advanced Tech., Inc., IPR2017-01411, 2018 WL 6204170, *12 (P.T.A.B. Nov. 27,
`
`2018) (“Upon weighing the competing extrinsic evidence …, we find Patent
`
`Owner’s extrinsic evidence is not sufficient to overcome the plain meaning….”).
`
`Even taking this extrinsic evidence into account, FDA acceptance criteria are not
`
`an appropriate guidepost for these claims. As Dr. Laskar explains, and Dr.
`
`Williams agrees, there is no requirement from the FDA that all acceptance criteria
`
`be set at ±10%. EX-1048, ¶¶9-13; EX-1054, 26:2-14. Additionally, a POSA
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`would have recognized that the FDA acceptance criteria and U.S.P. definitions
`
`serve a different purpose than the language of the challenged claims. EX-1048,
`
`¶¶7-10. Therefore, a POSA would not have understood “about” to mean ±10% in
`
`the context of the ’742 patent. Id., ¶¶9-13.
`
`Having failed to establish lexicography, the inquiry turns to the “criticality
`
`of the [numeric limitation] to the invention.” Ortho-McNeil Pharm., Inc. v.
`
`Caraco Pharm. Lab’ys, Ltd., 476 F.3d 1321, 1327 (Fed. Cir. 2007); Par Pharm.,
`
`Inc. v. Hospira, Inc., 835 F. App’x 578, 584 (Fed. Cir. 2020) (construing the
`
`claims based on “the purpose of the upper limit” of a range). Importantly, the ’742
`
`patent represents that the maximum “Net Vasoconstriction Benefit” peaks at
`
`around 0.03% brimonidine. EX-1001, 19:52-55. Patent Owner does not dispute
`
`that this curve represents the benefit of the invention after accounting for any
`
`adverse effects, such as rebound hyperemia, indicating that “around 0.03%” would
`
`
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`4
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`U.S. Patent No. 8,293,742
`be the optimal concentration for maximum benefit, not some arbitrary number
`
`below the peak. EX-1053, 86:7-17.
`
`The prosecution history further confirms that the patentee saw no
`
`meaningful difference between brimonidine concentrations of 0.025% and 0.03%.
`
`Figure 4 of the ’481 provisional is another, similar “graphical depiction … of the
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`variation of clinical effectiveness against concentration for compositions
`
`comprising … brimonidine….” EX-1011, p.68. Applicant explained that “[t]he
`
`net vasoconstrictive effect curve (vasoconstriction - rebound) is shown by the
`
`thicker light gray curve, and peaks at ~ 0.025% +/- 0.01% (intersecting dashed
`
`lines).” Id., p.111. Thus, the applicant represented that the maximum clinical
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`benefit occurs in the range of 0.015% to 0.035%,2 confirming that 0.025% is not
`
`critical. EX-1049, ¶22.
`
`Patent Owner places particular emphasis on the unlabeled curve in Figure 6
`
`that Patent Owner refers to as representing “Rebound Hyperemia,” but its reliance
`
`on this Figure is misplaced for several reasons. Paper-30, pp.33-35. First, Figure 6
`
`contains no information about how any observations reported were made; there is
`
`
`2 Unlike Patent Owner’s construction here, it appears that the applicant used
`
`± 0.01% to refer to a literal range around 0.025%, rather than referring to a range
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`that was 0.01% of 0.025% (± 0.00025%). EX-1048, ¶16.
`
`
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`5
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`Case IPR2022-00142
`U.S. Patent No. 8,293,742
`no scale on the y-axis; there are no error bars or any accounting for variability.
`
`EX-1001, Fig. 6; EX-1049, ¶¶13-17. Patent Owner has not made any
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`representation, nor can it, that Figure 6 contains data from a clinical study. EX-
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`1053, 89:2-90:3. Second, as the Board acknowledged, the patentee explained that
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`Figure 6 represents “finding[s] of the present invention” and that “the net
`
`effectiveness of brimonidine as a decongestant is greatest between about 0.01%
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`and about 0.03%; preferably, between about 0.012% and about 0.02%.” Paper-13,
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`pp.10-11; EX-1001, 19:52-57. Nothing in the text of the specification identifies
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`0.025% as having any criticality to the claimed redness reducing invention.3 See
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`Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1583 (Fed. Cir. 1996).
`
`Finally, Patent Owner’s argument also ignores Figure 2. Assuming the
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`figures have the same key, Dr. Noecker admitted that the rebound hyperemia
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`curves appear at different places in the two figures. See EX-1046; EX-1053, 91:2-
`
`93:9. These differences highlight the illustrative nature of these figures, and as a
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`result, a POSA would not have drawn exacting conclusions regarding any specific
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`data points. The specification does not distinguish between the clinical results at
`
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`3 In fact, Patent’s Owner’s representations regarding where 0.025% appears on the
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`x-axis conflict with the applicants’ representations to the Patent Office. EX-1049,
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`¶¶27-29.
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`
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`6
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`U.S. Patent No. 8,293,742
`0.025% and 0.03% brimonidine, and a POSA would not have imported such
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`meaning to these figures. EX-1049, ¶¶28-29.
`
`III. THE ’553 PATENT ANTICIPATES CLAIMS 1 AND 2
`Patent Owner does not dispute that the ’553 patent discloses administration
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`of 0.03% brimonidine to patients that underwent radial keratotomy. Paper-30,
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`p.41. Instead, Patent Owner advances the two claim construction arguments
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`discussed above—(1) whether the 0.03% brimonidine meets the “about 0.025%”
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`limitation of the claims and (2) whether the radial keratotomy patients in the ’553
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`patent suffer from an “ocular condition.” As discussed above, under the proper
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`claim constructions, 0.03% falls within the scope of the challenged claims, and
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`radial keratotomy is an “ocular condition.”
`
`Aside from claim construction, Patent Owner only disputes whether the
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`radial keratotomy patients would have had redness that was actually reduced.
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`Paper-30, pp.41-43. Here, Patent Owner incorrectly presumes that claims 1 and 2
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`require efficacy—i.e., redness to actually be reduced. See Paper-30, pp.40-42. But
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`the challenged claims contain no efficacy requirement, and there is no basis for
`
`reading one into the claims. Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No.
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`IPR2021-00881, 2022 WL 16842073, at *10 (P.T.A.B. Nov. 9, 2022) (“We reject
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`Patent Owner’s proposed construction because it requires importing limitations
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`into the claims.”). At most, the claims require that the composition be
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`U.S. Patent No. 8,293,742
`administered with the intent to reduce redness. Id., *8. Example 1 of the ’553
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`patent discloses such a method.
`
`The ’553 patent discloses administering 0.03% brimonidine with the intent
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`of monitoring for a reduction in signs of ocular inflammation. EX-1004, 4:45-5:2.
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`It is undisputed that redness is a sign of ocular inflammation. EX-1004, 5:38-40;
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`EX-2020, ¶146. Therefore, Example 1 of the ’553 patent discloses a method that
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`sought to reduce redness by administering low dose brimonidine, as claimed in the
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`challenged claims, and the inquiry should end there.
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`Assuming, however, that the claims require an actual reduction of redness,
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`the ’553 patent also inherently discloses this feature. As the Board recognized, the
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`prior art need not recognize a claimed feature in order to anticipa
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