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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
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`OCULAR THERAPEUTIX, INC.
`Petitioner
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`v.
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`MATI THERAPEUTICS INC.
`Patent Owner
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`US Patent No. 9,849,082
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`Inter Partes Review No. IPR2019-00448
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`_______________
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`PETITIONER REPLY TO
`PATENT OWNER RESPONSE
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`Patent No. 9,849,082
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`Attorney Docket No. 129285-00013
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`Page
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`TABLE OF CONTENTS
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`INTRODUCTION .................................................................................................. 1
`I.
`SPECIFICATION ......................................................................................... 2
`A.
`Therapeutic Level for an Extended Period of Time” ........................... 2
`B.
`The Claims Do Not Require “Lasting” Color ...................................... 3
`C.
`Canaliculus such that Transillumination Is Required .......................... 5
`II. MATI APPLIED A FLAWED PARADIGM AND FLAWED
`REASONING TO REACH THE WRONG CONCLUSIONS ...................... 8
`A.
`The POSA, If Not a Chemist, Would Rely on a Chemist .................... 9
`B. Williams Did Not Provide a Legitimate Perspective of a POSA ....... 10
`C. Williams’ Reasoning Regarding Anticipation by Pritchard Is
`Flawed .............................................................................................. 12
`D. Williams’ Reasoning Regarding Obviousness in View of
`Pritchard and Gillespie Is Flawed ..................................................... 18
`E. Williams’ Reasoning Regarding Hellberg’s Teaching of
`Travoprost Is Flawed ........................................................................ 24
`CONCLUSION .................................................................................................... 26
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`MATI’S READS INTO THE CLAIMS FEATURES
`UNSUPPORTED BY THE CLAIM WORDING AND
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`The Claims Do Not Require “Sustained Release at the Desired
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`The Claims Do Not Require “Placement” Wholly within the
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`FEDERAL CASES
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`Attorney Docket No. 129285-00013
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`TABLE OF AUTHORITIES
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`Page(s)
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`In re GPAC Inc.,
`57 F.3d 1573 (Fed. Cir. 1995) ............................................................................ 8
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`Iovate Health Sciences, Inc. v. Bio-engineered Supplements & Nutrition, Inc,
`586 F.3d 1376 (Fed. Cir. 2009) .......................................................................... 1
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`Kara Tech. Inc. v. Stamps.com Inc.,
`582 F.3d 1341 (Fed. Cir. 2009) .......................................................................... 3
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`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .......................................................................... 7
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`INTRODUCTION
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`Despite arguing that no claim construction is necessary and that the claims
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`have their plain and ordinary meaning (POR, 25-27), Patent Owner Mati
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`Therapeutics and its expert, Dr. Williams, distinguish the prior art by importing
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`limitations into the claims that are neither based on actual claim wording nor
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`required by the specification. For instance, they read into the claims (1) “sustained
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`release” of an effective amount of a drug for an “extended period,” (2) a “lasting”
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`distinguishing color that is retained in the device for an extended period, and (3)
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`placement of the insert all the way into the canaliculus, with no portion exposed
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`above the punctum, such that transillumination is the only method for visualizing
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`it. These unclaimed and unsupported features are not relevant to patentability.
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`Iovate Health Sciences, Inc. v. Bio-engineered Supplements & Nutrition, Inc., 586
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`F.3d 1376, 1382 (Fed. Cir. 2009) (rejecting argument that reference did not
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`anticipate because it did not achieve unclaimed effectiveness).
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`While Dr. Williams purports to consider the prior art from the perspective of
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`a person of ordinary skill in the art (POSA), he fails do so. Williams did not
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`carefully review the primary reference, Pritchard. He was not familiar with
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`relevant prior art and did not even know that a POSA is deemed to be familiar with
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`the relevant art. Rather than acknowledge existing connections between various
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`teachings, Williams parroted hearsay he learned from some unidentified chemist
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`and relied on documents that actually contradict his points. In sum, Williams’
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`analysis and opinions were fatally flawed.
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`I. MATI’S READS INTO THE CLAIMS FEATURES UNSUPPORTED
`BY THE CLAIM WORDING AND SPECIFICATION
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`A. The Claims Do Not Require “Sustained Release at the Desired
`Therapeutic Level for an Extended Period of Time”
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`Mati and Williams read into the claims a requirement that the drug delivery
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`system must provide a “sustained release of the drug at the desired therapeutic
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`level for an extended period of time.” POR, 2; Ex.2014, ¶23; Ex.1043, 187:12-22.
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`Mati then tries to distinguish Pritchard on this basis. POR, 19. This unclaimed
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`limitation taints not just Mati’s arguments but also Williams’s opinions. In fact,
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`the leading question that Mati posed to Williams before he had developed any
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`allegedly independent opinion was “whether Pritchard had the ability to deliver a
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`sustained release of the drug at a therapeutic level for an extended period.”
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`Ex.1043, 213:6-214:9. Without having any basis in the claims or the specification,
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`Williams applied Mati’s suggested “sustained release” construction.
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`Williams only later admitted that “sustained therapy” over time is not found
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`in the claims. Ex.1043, 184:14-185:1; see also 185:6-8 (“Taken in isolation, Claim
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`1 does not require prolonged or extended release, sustained release of the drug”).
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`He then posited that the patent merely “implied” this requirement. Id., 187:1-11.
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`Nothing in the specification, however, requires sustained release over time.
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`In contrast to Claim 1 of the ‘082 Patent, Claim 1 of related U.S. Pat. No.
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`7,998,497 expressly requires “release [of] the therapeutic agent at a desired
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`therapeutic level over a sustained period.” Ex. 1051. That the inventors expressly
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`recited “sustained release” in a parent patent but not in the ‘082 Patent shows that
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`the ‘082 Patent does not require “sustained release” over time. Kara Tech. Inc. v.
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`Stamps.com Inc., 582 F.3d 1341, 1347 (Fed. Cir. 2009) (“Here, when the inventor
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`wanted to restrict the claims to require the use of a key, he did so explicitly”).
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`Even if Claim 1 somehow required a sustained release over an extended
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`period, which it does not, the ‘082 Patent explains that an extended period “may
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`mean a relatively short period of time, for example minutes or hours ... through
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`days or weeks ... or longer.” Ex.1001, 23:59-63 (emphasis added). Mati failed to
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`consider this teaching in its attempt to distinguish the prior art.
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`B.
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`The Claims Do Not Require “Lasting” Color
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`Although “lasting” likewise does not appear in the claims, Mati and
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`Williams try to distinguish the prior art by arguing that the “distinguishing color”
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`must be “lasting” and retained in the hydrogel body for an extended period. POR,
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`21, 40-42, 50-51; Ex.2014, ¶¶40, 68, 70, 92-93; Ex.1043, 81:20-82:11. The
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`claims, however, simply require “a distinguishing color to show placement.”
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`Nowhere does the ‘082 Patent teach that color must endure under all conditions,
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`which Mati erroneously reads into “distinguishing color.” Ex.1043, 137:21-138:3;
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`138:21-139:4. Indeed, as Williams admits, the patent does not even teach how to
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`make a plug with a “lasting” and distinguishing color:
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`Q.
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`So where is the disclosure in the ‘082 patent of how to make a
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`hydrogel plug with a lasting and distinguishing color?
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`[objection]
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`A. THE WITNESS: That is not described within the ‘082 patent that
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`I am able to find.
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`Ex.1043, 141:24-142:5.
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`Indeed, the ‘082 Patent has virtually no teaching on color. Dr. William
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`admits that the only disclosure of a “distinguishing color” lies at Columns 20:67-
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`21:5. See Ex.1043, 132:1-14. But this section is silent on how long the color must
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`be retained.
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`Moreover, the ‘082 Patent contemplates a “burst release” of the therapeutic
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`agent by using an erodible or highly soluble polymer that is “immediately
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`dissolved” in the tear film of the canaliculus such that the therapeutic agent within
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`the polymer body “is immediately released.” Ex, 1001, 25:66-26:19. Thus, color
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`“lasting” beyond placement is not relevant to an invalidity analysis.
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`Even if “lasting” were read into the claims, Ocular’s drug delivery and
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`hydrogel expert, Dr. Lowman, explains that “hydrogel devices worn on the eye
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`were known to retain their color at the relevant time.” Ex.1052, ¶80. “For
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`example, hydrogel contact lenses were known ... [that] retained color under
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`physiological conditions.” Ex.1052, ¶80. Further, Dr. Lowman explains that
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`Pritchard discloses “two different sets of hydrogel devices for delivering [an active
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`agent] with a sustained color.” Ex.1052, ¶83. Additionally, Pritchard, via its
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`incorporation of the ‘132 Pritchard Provisional, discloses the “Opaque Herrick
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`Lacrimal Plug” as a predicate device (Ex.1052, ¶80 (citing Ex. 1011, 40-41)), and
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`an ophthalmologist would recognize that the opaque Herrick plug “reveal[ed] its
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`presence” to a clinician “once inserted” and under transillumination (Ex.1052, ¶80-
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`81 (citing Ex.1040, 1)). Accordingly, “an ophthalmologist would have known that
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`a color can be sufficiently sustained in a hydrogel punctal plug under physiological
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`conditions to show placement of a punctal plug in the lacrimal canaliculus.”
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`Ex.1052, ¶84.
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`C. The Claims Do Not Require “Placement” Wholly within the
`Canaliculus such that Transillumination Is Required
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`Contrary to Mati’s arguments, the ‘082 Patent does not require insertion of
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`the system into the canaliculus such that no surface remains exposed at or above
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`the punctum and transillumination is required to distinguish the device. See POR
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`at 38, 47.
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`As Williams admits and other evidence confirms, the ordinary meaning of
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`the phrase “placement … in the lacrimal canaliculus” includes an act or instance
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`of placing. See Ex.1043, 37:12-38:19 (“placement in the lacrimal canliculus”
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`means “manipulating … into the position of the lacrimal canaliculus”); POR 14
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`(“post-placement”); Ex.2014, ¶11 (“tools for the placement”); Ex.1020, 5
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`(“Before placement”); Ex.1011, 27 (“delay the placement”); Ex.1023, 3:43-48
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`(“permitting placement of the punctum plug into position”); Ex.1041, ¶[0053]
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`(“during … placement”).
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`Placement also refers to at least two possible system locations: (a) wholly
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`within and (b) only partially within the lacrimal canaliculus. POR 5-6; Ex.2014,
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`¶¶28, 37; Ex.2021, ¶[0012] (“Punctal plugs are configured to fit at least partially
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`within the lacrimal caniliculus ….”) (emphasis added). According to Williams,
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`“Claim 1 does not specify that it would be one or the other placement.” Ex.1043,
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`190:13-191:3.
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`Thus, the plain meaning of “placement … in the lacrimal canaliculus”
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`encompasses the act of placing the system, as well as system locations both
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`wholly within and only partly within the lacrimal canaliculus.
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`Indeed, after insertion in the canaliculus, all of the embodiments in the ‘082
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`Patent feature an “exposed surface” at or above the punctum. See, e.g., Ex.1001,
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`FIG. 1G, 182A (“exposed surface area”); FIG. 2A, 210E; FIG. 2B, 212A; FIGS.
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`2C-2D, 214A; FIG. 2E, 216A; FIG. 2F, 260A; FIG. 2G, 262A; FIG. 2H, 264A;
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`FIG. 2I, 266A; FIG. 2J, 268A; FIG. 2K, 269A (all labeled “exposed surface”);
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`FIG. 2L, 232A; FIG. 2M, 242A (both labeled “surface … on exposed end”); FIG.
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`3A, 332; FIG. 3B, 372; FIGS. 4A-4B, 412 (all labeled “exposed surface”); FIG.
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`8C (840 at punctum 800A); FIG. 9C (collar 952 to rest outside punctum); FIG. 9D
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`(flanges 964 to rest outside punctum); FIG. 9F (same, see 17:22-26); FIGS. 10A-
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`10C (“end of drug core is exposed”); FIG. 11 (wings 1112 rest outside punctum).
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`The drug is delivered “from the exposed surface of the drug core into the tear
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`film.” Ex.1001, 28:46-48.
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`The ‘082 Patent does not disclose an embodiment designed to reside wholly
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`within the canaliculus, and Mati has identified no embodiment consistent with the
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`“no exposed surface” construction it uses to distinguish prior art. Mati’s argument
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`that “placement” is limited to a system location wholly within the canaliculus
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`contradicts the specification and is therefore wrong. Phillips v. AWH Corp., 415
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`F.3d 1303, 1316 (Fed. Cir. 2005).
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`Further, as Williams concedes, the patent never mentions or suggests
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`transillumination. Ex.1043, 132:15-18; 133:8-9. Nor does that patent suggest that
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`an ophthalmologist is needed to detect the claimed distinguishing color. Ex.1001,
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`20:67-21:5 (distinguishing color “readily detected by the patient.”) (emphasis
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`added). Transillumination is a technique not taught to patients. Ex.1043, 34:7-10.
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`And Williams could not identify any device wholly within the canaliculus that
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`could be readily detected by a patient. Ex.1043, 130:7-131:19.
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`Given the limited disclosure of color in the ‘082 Patent, Dr. Williams relies
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`on technology developed by Herrick for his understanding of the claimed
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`“distinguishing color.” Ex.1043, 141:24-142:5; Ex.2014, ¶66. Williams identifies
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`the opaque Herrick lacrimal plug as the only example of a plug with a
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`distinguishing color
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`to
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`show placement
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`in
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`the canaliculus
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`(during
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`transillumination). Ex.1043, 134:2-7. At the same time, Williams was not
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`familiar with the 2002 Herrick Publication, cited on the face of the ‘082 Patent, in
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`which Herrick discloses the transillumination technique and how to modify plugs
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`so that they are distinguishable in the canaliculus during transillumination.
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`Ex.1043, 104:12-114:6 (testifying about Ex.1041).
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` Similarly, Williams
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`discounted the Opaque Herrick Lacrimal Plug described in the ’132 Pritchard
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`Provisional as somehow not relevant. Ex.1043, 210:24-213:17. Dr. Williams’s
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`inconsistent approach to the Herrick technology is explained by Mati’s
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`interpretation of the relevant art as limited to “drug delivery ophthalmic devices.”
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`Id.; POR, 16.
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`II. MATI APPLIED A FLAWED PARADIGM AND FLAWED
`REASONING TO REACH THE WRONG CONCLUSIONS
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`“The person of ordinary skill in the art [POSA] is a hypothetical person
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`who is presumed to know the relevant prior art.” In re GPAC Inc., 57 F.3d 1573,
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`1579 (Fed. Cir. 1995). But Mati did not inform its expert that the POSA is
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`presumed to know all of the relevant prior art. Ex.1043, 107:2-8; Ex.2014 ¶¶20,
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`52-53, 76-81. In fact, Williams did not consider all of the relevant art or, for that
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`matter, carefully review and consider the primary reference, Pritchard. See
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`Sections II.C-.D.
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`Contrary to Mati’s argument, the relevant art is not limited to “drug
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`delivery opthalmic devices.” POR, 16. In his deposition, Williams agreed that
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`the ‘082 patent “relate[s] to punctal plugs with and without drug delivery
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`capabilities.” Ex.1043, 55:7-14 (emphasis added). See also Ex.1001, 1:21-24
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`(The ‘082 patent relates to “implants for use in or near the nasolacrimal drainage
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`system, with embodiments providing canalicular implants, lacrimal sac implants,
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`punctal plugs and punctal plugs with drug delivery capabilities”). But in his
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`declaration, except when it suited Mati’s purposes (as with the Herrick plug),
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`Williams took the position that only certain drug delivery ophthalmic device art is
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`relevant. Ex.2014 ¶¶20, 32-34.
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`A. The POSA, If Not a Chemist, Would Rely on a Chemist
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`As an ophthalmologist assisting with the pharmaceutical formulations of
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`punctal plugs, Williams relies on a chemist. Ex.1043, 167:15-168:7 (for materials
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`properties, including the color of metallic silver); 12:3-13:1 (for formulation of
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`punctal plugs). Williams testified that every ophthalmologist involved in
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`developing a drug delivery device works with a chemist. Ex.1043, 36:15-37:1;
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`167:22-168:7; 224:23-226:2; Ex.2025, 7. Mati did not offer testimony from a
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`chemist, and instead had Williams parrot what he was told by some unidentified
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`chemist. Ex.1043, 167:15-168:4. In contrast, Ocular has offered the direct
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`testimony of Dr. Lowman, an actual chemist, who has designed drug delivery
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`devices and is an expert in hydrogels. As seen below, Lowman rebuts Williams’
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`opinions on issues involving material compositions and potential interactions. See
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`Ex.1052.
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`B. Williams Did Not Provide a Legitimate Perspective of a POSA
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`Williams was unaware that a POSA is presumed to be familiar with the
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`relevant art. Ex.1043, 107:2-8; Ex.2014, ¶¶20, 52-53, 76-81. He discounted art
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`that he deemed irrelevant to the unclaimed features that he read into the claims,
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`such as “sustained release of drug at a therapeutic level for an extended period.”
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`Ex.1043, 210:24-214:9.
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`Williams was not familiar with some of the most relevant prior art. For
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`example, Williams identified the Opaque Herrick plug as the only example of
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`prior art featuring the claimed distinguishing color (Ex.1043, 62:5-11) and
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`explained that Herrick established a “standard [transillumination] practice, to
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`examine an eyelid to see if there was a colored plug in the canaliculus.” Ex.1043,
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`134:8-19. He used Herrick’s technology as the basis for his understanding of
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`what the claimed “distinguishing color …” meant in the context of the ‘082
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`patent. Ex.1043, 134:8-136:14.
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`On the other hand, although it was cited in the ‘082 Patent (Ex.1001, 2
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`(citing Ex.1041)), Williams was not familiar with the 2002 Herrick Publication
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`describing the use of transillumination to show a pigmented plug entirely within
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`the lacrimal canaliculus (Ex.1043, 103:15-114:6 (discussing Ex.1041)). Williams
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`did not consider the disclosure in the 2002 Herrick Publication of how to pigment
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`a hydrogel plug so that it is visible in the canaliculus during transillumination.
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`Ex.1041, [0151], [0173]-[0180]. In other words, while relying on it for his
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`understanding of the ‘082 Patent, Williams did not consider the enablement of the
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`Opaque Herrick plug and its visualization during transillumination as within the
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`knowledge of a POSA. Ex.1041, [0151], [0173]-[0180].
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`Williams also did not carefully review the primary reference, Pritchard.
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`Ex.1043, 192:10-194:6 (correcting his erroneous declaration testimony that
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`“Pritchard describes two parallel sets of the silver containing … occlusive devices
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`made by the identical process” by admitting the processes were not identical).
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`Nor did he consider a provisional application Pritchard incorporated by reference
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`and that was cited in both the Petition and Institution Decision. Compare
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`Ex.2014, ¶13 and Exhibit B (not identifying Ex.1012 as material Williams
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`considered) with Pet. 34, 37-38, 40-41, 49, 51-53 (citing Ex.1012) and Inst. Dec. 7
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`(citing Ex.1012 and characterizing it as “incorporated by reference by Pritchard”).
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`Misled by Mati, unfamiliar with relevant art, and having not carefully read
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`Pritchard, Williams did not form a legitimate opinion as to whether Pritchard
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`would put a POSA in possession of the invention.
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`C. Williams’ Reasoning Regarding Anticipation by Pritchard Is
`Flawed
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`According to Lowman, Williams’s opinion that Pritchard fails to teach a
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`POSA how to design a punctal plug for the delivery of silver is unwarranted.
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`Ex.1052, ¶25. Unlike Williams, Lowman carefully reviewed Pritchard’s
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`disclosure, including material incorporated by reference. Ex.1052, ¶¶25-37, 67-
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`74. After doing so, Lowman could “identify no aspect of the design of a punctal
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`plug for delivery of silver that is not taught by Pritchard.” Ex.1052, ¶45.
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`“Pritchard discloses (a) swellable punctum plugs and processes for making such
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`plugs; (b) that its devices can include and slowly elute therapeutical agents; and
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`(c) exemplary hydrogel punctal plugs comprising silver as a therapeutic agent and
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`processes for making such plugs.” Ex.1052, ¶25. “[A] silver punctal plug in the
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`nasolacrimal system would deliver silver.” Ex.1052, ¶25. Accordingly,
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`“Pritchard teaches how to design a punctal plug for delivery of silver.” Ex.1052,
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`¶45.
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`Lowman disagrees with Williams’ speculation that “the amount of silver
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`disclosed in Pritchard … would be ineffective to provide an antimicrobial effect.”
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`Ex.1052, ¶38. According to Lowman, “the amount of silver in the exemplary
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`hydrogel drug and therapeutic agent delivery devices disclosed in Pritchard would
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`provide an antimicrobial effect because [1] silver ionizes in the presence of tissue
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`fluids, such as tears, to release biologically active ions and [2] because silver has
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`an antimicrobial effect even at very low concentrations and there are no minimum
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`performance standards for antimicrobials.” Ex.1052, ¶44.
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`Lowman also disagrees with Williams’s conclusion as to Pritchard’s
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`disclosure of an “intracanaliculuar plug for insertion into a lacrimal canaliculus of
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`a patient, which has a distinguishing color to show its placement.” Ex.1052, ¶46.
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`Williams defines an “intracanalicular plug” as “a plug that is introduced through
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`the punctal, so the whole body of the plug is within the canaliculus and is not
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`visible from outside.” Id. Lowman notes that “the ‘132 Pritchard Provisional
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`references the ‘Opaque Herrick Lacrimal Plug’” and describes it as composed of a
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`hydrogel forming materials. Ex.1052, ¶49. Lowman reports that the 2002 Herrick
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`Publication, which is cited on the face of the ‘082 patent (Ex.1001, 2 (citing
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`Ex.1041)), discloses how to make such a plug and how it could be seen in the
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`canaliculus during transillumination. Ex.1052, ¶¶50-52 (citing Ex.1041).
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`In Lowman’s opinion, “[b]ased on what was known in the art … including
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`the existence of an Opaque Herrick Lacrimal Plug comprising a hydrogel forming
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`material and the 2002 Herrick Publication’s disclosure of how to make such a
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`plug and how it could be seen in the canaliculus during transillumination,
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`Pritchard discloses an intracanaliculuar punctal plug for insertion into a lacrimal
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`canaliculus of a patient with a distinguishing color to show its placement.”
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`Ex.1052, ¶54. A hypothetical “ophthalmologist would have known that hydrogel
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`plugs could be made visible during transillumination in the canaliculus and that
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`that feature is desirable and achievable.” Id.
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`Williams testified that “[a POSA] would be led to believe that certain
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`hydrogels could sustain color.” Ex.1043, 116:12-14. Nonetheless, Williams
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`“would not assume that the hydrogels described by Pritchard, that in all cases
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`erode or are digested or disappear, would be capable of maintaining the color
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`within that hydrogel.” Ex.1043, 116:14-22. But the ‘082 Patent also discloses
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`such dissolving hydrogels. Ex.1001, 25:66-26:19. And according to Lowman,
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`“Pritchard indicates that not all of its hydrogels would erode, be digested, or
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`disappear.” Ex.1052, ¶59 (citing Ex. 1010, [0036]-[0043]). Further, “an
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`experienced formulator would have known that hydrogels can be designed to
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`sustain color until they have degraded.” Ex.1052, ¶58.
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`Unlike Williams, Lowman noted that “Pritchard claims a punctum plug,
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`comprising silver, that ‘degrades in less than about seven days in the punctal
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`opening of the patient.’” Ex.1052, ¶60 (quoting Ex.1010, Claim 1, Claim 13).
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`Lowman points out that “Pritchard discloses that both sets of hydrogel devices for
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`the delivery of silver retain their light straw color for at least a week.”1 Ex.1052,
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`¶60 (citing Ex.1010, [0138], [0140]). Thus, Lowman concludes, “[b]oth of
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`Pritchard’s exemplary hydrogel devices for delivery of silver were observed to
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`retain their color throughout the period before which Pritchard claimed silver
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`plugs would have degraded.” Ex.1052, ¶60 (citing Ex.1010, [0138], [0140]).
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`Lowman further concludes that Pritchard discloses silver hydrogel devices
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`featuring a distinguishing color that would show placement of the device in the
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`lacrimal canaliculus of the patient. Ex.1052, ¶¶61-65. “Particularly as compared
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`to a clear and colorless hydrogel device, … the light straw color … makes the
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`devices distinguishable to show placement of such a device in the lacrimal
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`canaliculus during that process.” Ex.1052, ¶63. “Based on the prior art, a POSA
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`
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`1 Lowman notes that Pritchard added a step to the process in making the
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`second set of hydrogel devices and does “not attribute difference in color retention
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`… to any difference between placing the samples in physiological saline solution
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`and in physiological saline solution / distilled water.” Ex.1052, ¶¶35, 60.
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`would have known that silver could be used in the eye.” Ex.1052, ¶64 (citing Ex.
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`1061, 368 (“nearly 100 years of experience with silver nitrate prophylaxis
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`opthalmia neonatorum ….”)). Lowman explains that the silver in Pritchard’s
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`hydrogel devices, as a known imaging agent and “energy obstructing material” in
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`accordance with the 2002 Herrick Publication, “would make the devices easier to
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`see during transillumination of such a device in the lacrimal canaliculus as
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`described in Ex.1041.” Ex.1052, ¶64. According to Lowman, “[t]he [light straw]
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`color observed by Pritchard would be distinguishing both during placement in the
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`lacrimal canaliculus and during transillumination of the device in the canaliculus.”
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`Ex.1052, ¶65.
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`Without having read the ‘368 Pritchard Provisional (Ex.2014, ¶13, Exhibit
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`B), Williams concluded “Pritchard does not recite dexamethasone” (Ex.2014,
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`¶60). In fact, Pritchard incorporates the ‘368 Pritchard Provisional by reference.
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`Ex.1010, ¶[0001]. The ‘368 Pritchard Provisional sets forth “anti-inflammatory
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`agents
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`such as dexamethasone,” and “[c]orticosteroids
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`such as …
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`dexamethasone.” Ex.1012, 6, 10. Lowman describes how the ‘368 Pritchard
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`Provisional and Pritchard fit together. Ex.1052, ¶¶25-37, 67-74. Lowman
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`explains how Pritchard enables one of skill in the art to add dexamethasone to a
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`silver hydrogel device. Ex.1052, ¶67-74. According to Lowman, “[o]nly routine
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`experimentation would be involved in modifying the process disclosed in
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`Pritchard.” Id. “Moreover, a chemist would expect the dexamethasone to be
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`released from the resulting hydrogel device faster than the silver because the
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`dexamethasone is smaller than the silver.” Id. Lowman concludes “Pritchard
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`discloses the use of dexamethasone as a therapeutic agent in its hydrogel plugs for
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`drug delivery.” Ex.1052, ¶67.
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`According to Lowman, “the difference between silver and dexamethasone,
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`along with what was known in ophthalmology at the relevant time, provided
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`reason to readily envision the combination of the anti-inflammatory corticosteroid
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`dexamethasone disclosed in Pritchard with Pritchard’s antimicrobial silver
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`hydrogel punctal plug, as Pritchard suggested, so that each could provide the
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`function it was known to perform and the benefit of both could be provided
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`together.” Ex.1052, ¶74. For example, a “newly found interest in using topical
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`anti-inflammatory agents to treat DES” was reported in 2002. Ex.1028, 10. As
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`the 2004 Physicians’ Desk Reference for Opthalmic Medicines (PDR-O) explains,
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`“Corticosteroids are the most commonly used [medications to treat ocular
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`inflammation].” Ex.1045, 21. In fact, dexamethasone was one of the six topical
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`(steroidal) anti-inflammatory agents that were commercially-available in 2004.
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`Ex.1045, 21. “Dexamethasone … is not an equivalent to or interchangeable with
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`silver.” Ex.2014, ¶59. And in 2004, “it [was] appreciated that steroids, when
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`used in conjunction with appropriate antimicrobial … agents, may help to prevent
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`more serious ocular damage.” Ex.1045, 21. Additionally, the ‘368 Pritchard
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`Provisional specifically discloses “hydrogels for delivering antimicrobial agents,
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`[and/or] medicaments … to the site of implantation.” Ex.1012, 51.
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`D. Williams’ Reasoning Regarding Obviousness in View of Pritchard
`and Gillespie Is Flawed
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`Williams’s perspective on the combination of Pritchard and Gillespie was
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`flawed because he (a) did not carefully read Pritchard, including its provisional
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`applications incorporated by reference; (b) was not familiar with all of the relevant
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`art, such as the 2002 Herrick publication; and (c) let Mati’s improper claim
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`construction cloud his view of what art was relevant in the first place.
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`Contrary to Williams’s suggestion, Gillespie does not teach away from the
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`use of a punctal plug for drug delivery. Gillespie teaches that punctal plugs are
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`used to treat dry eye syndrome (DES). Ex.1015, [0001]-[0005]. At the time, “a
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`newly found interest in using topical anti-inflammatory agents to treat DES” was
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`reported in the relevant art. Ex.1028, 10. Lazar, a publication filed as an exhibit to
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`the First ‘082 Provisional (Ex.1002, 45-77), taught that “it is not unusual for up to
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`85% of
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`topically applied agents
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`to be
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`removed by
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`the eye’s blink
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`mechanism/reflex” and that “topical eye drops … can drain from the eye through
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`the nasolacrimal duct.” Ex. 1002, 47 (Lazar, [0005]). Accordingly, Lazar taught
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`that a punctal insert that delivers drugs would be desirable. Ex. 1002, 48 (Lazar,
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`[0007]). Apparently, Williams did not review the exhibits that document this
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`motivation in the relevant art at the time. Ex.2014, ¶13 and Exhibit B (not listing
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`Ex.1028 or Ex.1002 as material Williams considered).
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`After considering the relevant art, which Williams largely ignored, Dr.
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`Lowman concluded that Gillespie’s teachings are not limited to Silastic rubber
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`devices. Ex.1052, ¶77. Gillespie teaches that, aside from the coloring agent,
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`“[t]he rest of the plug body may be composed of any suitable material, including
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`those presently used in the manufacture of such devices.” Ex.1015, [0006].
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`Lowman notes that “the ‘132 Pritchard Provisional references various punctum
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`plugs composed of hydrogel forming materials as predicate devices.” Ex.1052,
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`¶77. As such, “one familiar with the relevant art would understand that suitable
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`materials include hydrogel forming materials then used in the manufacture of
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`punctum plugs.” Id. In short, according to Lowman, “Gillespie contemplates a
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`punctal plug made of hydrogel polymers.” Id.
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`Gillespie teaches “a substance causing … contrast with surrounding tissue,
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`such that the use of the substance causes the plug to be more easily visualized than
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`if the substance were not present.” Ex.1015, [00
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