UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`FLATWING PHARMACEUTICALS, LLC and
`MYLAN PHARMACEUTICALS, INC.,
`Petitioners,
`
`v.
`
`ANACOR PHARMACEUTICALS, INC.,
`Patent Owner.
`
`Case Nos. IPR2018-00168, -00169, -00170, and -001711
`
`U.S. Patent Nos. 9,549,938, 9,566,289, 9,566,290, and 9,572,823
`______________________
`
`DECLARATION OF STEPHEN KAHL, PH.D
`IN SUPPORT OF PETITIONER’S REPLY TO PATENT OWNER’S
`RESPONSE
`
`1 Case Nos. IPR2018-01358, -01359, -01360, and -01361 have been joined with
`these proceedings.
`
`FlatWing Ex. 1047, p. 1
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`FLATWING PHARMACEUTICALS, LLC and
`MYLAN PHARMACEUTICALS, INC.,
`Petitioners,
`
`v.
`
`ANACOR PHARMACEUTICALS, INC.,
`Patent Owner.
`
`Case Nos. IPR2018-00168, -00169, -00170, and -001711
`
`U.S. Patent Nos. 9,549,938, 9,566,289, 9,566,290, and 9,572,823
`______________________
`
`DECLARATION OF STEPHEN KAHL, PH.D
`IN SUPPORT OF PETITIONER’S REPLY TO PATENT OWNER’S
`RESPONSE
`
`1 Case Nos. IPR2018-01358, -01359, -01360, and -01361 have been joined with
`these proceedings.
`
`FlatWing Ex. 1047, p. 1
`
`
`
`Declaration of Stephen Kahl, Ph.D
`
`1.
`
`I, Stephen Kahl, Ph.D., hereby declare that the following is true and
`
`correct. I previously provided a declaration filed as Ex. 1003 in support of Paper
`
`#1, Petition for Inter Partes Review, and my testimony from that first Declaration
`
`remains the same. I am competent to make this Declaration based upon my
`
`personal knowledge and technical expertise, which I addressed in my first
`
`declaration.
`
`2.
`
`Dr. Reider bases much of his testimony on what he calls the
`
`“promiscuous” nature of boron. (IPR2018-00168, Ex. 2013, ¶¶ 24–30;
`
`IPR2018-00169, Ex. 2013, ¶¶ 27–33; IPR2018-00170, Ex. 2013, ¶¶ 28–34;
`
`IPR2018-00171, Ex. 2013, ¶¶ 22–28.) I am informed that the Board rejected this
`
`same line of reasoning in its previous decision in rejecting Patent Owner’s
`
`arguments about supposed toxicity concerns:
`
`Moreover, boron’s allegedly “promiscuous” behavior does not
`dissuade a person of ordinary skill in the art from considering boron-
`containing compounds generally, or tavaborole in particular.
`
`(Ex. 1014 at 27.) I agree with the Board, that a POSA would not have been
`
`dissuaded from considering boron-containing compounds generally, or tavaborole
`
`in particular. Instead, a POSA would have considered a boron-containing
`
`compound like tavaborole a suitable candidate for development, using routine
`
`procedures such as dose ranging studies as discussed by Dr. Murthy.
`
`1
`
`FlatWing Ex. 1047, p. 2
`
`
`
`Declaration of Stephen Kahl, Ph.D
`
`3.
`
`Dr. Reider bases much of his testimony on the supposed degradation
`
`of boron, through hydrolysis or oxidation. (IPR2018-000168, Ex. 2013, ¶ 37;
`
`IPR2018-00169, Ex. 2013, ¶ 40; IPR2018-00170, Ex. 2013, ¶ 41; IPR2018-00171,
`
`Ex. 2013, ¶ 35.) However, Dr. Reider admits he did not consider the kinetics of the
`
`reaction, which concern how long any such degradation would take. (Ex. 1045,
`
`Reider Dep. at 84:7–85:5 (“I have not seriously thought about the rate . . . .”).)
`
`4.
`
`In fact, concerning the degradation of boronic acids and esters, the
`
`kinetics of the reaction (i.e., the degradation of boronic acids and esters) are
`
`usually extremely slow. Thermodynamically, the degradation of boronic acids and
`
`esters is a favorable reaction and, given enough time, it will occur. But in many
`
`cases, the rate of the reaction is slow enough that noticeable degradation could take
`
`years or decades. The rate of reaction is sufficiently slow that these compounds can
`
`be formulated into products having a commercially useful shelf life.
`
`5.
`
`For tavaborole in particular, the rate of decay is extremely slow,
`
`orders of magnitude longer than the treatment period in which tavaborole
`
`penetrates the nail, and sufficiently slow to permit formulation of a product having
`
`a useful shelf life. As such, it would have no bearing on the use of tavaborole as a
`
`pharmaceutical generally. It would also have no bearing on the concentration of
`
`tavaborole that a person of ordinary skill in the art would choose to include in a
`
`pharmaceutical formulation.
`
`2
`
`FlatWing Ex. 1047, p. 3
`
`
`
`Declaration of Stephen Kahl, Ph.D
`
`6.
`
`Building on his failure to consider the reaction kinetics, Dr. Reider
`
`also testifies that tavaborole in Brehove would not penetrate the nail plate but
`
`would instead undergo hydrolysis to boric acid before doing so. (IPR2018-00168,
`
`Ex. 2013 ¶¶ 66–67, 69; IPR2018-00169, Ex. 2013 ¶¶ 69–70, 72; IPR2018-00170,
`
`Ex. 2013 ¶¶ 70–71, 73; IPR2018-00171, Ex. 2013 ¶¶ 64–65, 67.) I am informed
`
`that the Board has previously determined to the contrary, that a POSA “would have
`
`had a reasonable expectation that administering tavaborole topically would
`
`penetrate the nail.” (Ex. 1014 at 24 (emphasis added).) I agree with the Board that
`
`a POSA would have had a reasonable expectation that administering tavaborole
`
`topically would penetrate the nail and would not instead undergo hydrolysis to
`
`boric acid so, in part because, as explained supra, the kinetics of the reaction are
`
`sufficiently slow that tavaborole would have more than enough time to penetrate
`
`the nail before any such hydrolysis would occur.
`
`7. Moreover, Austin expressly discloses using tavaborole as an
`
`antifungal on an “aqueous medium”:
`
`If the medium to be protected is an aqueous medium, the carrier is
`preferably water or a water-miscible organic solvent or mixture
`thereof. Examples of suitable water-miscible organic solvents are
`acetic acid, N,N-dimethylformamide, dimethylsulphoxide, N-methyl-
`2-pyrrolidine, alcohols such as ethanol or glycols such as ethylene
`glycol, propylene glycol and dipropylene glycol and lower C1-4-alkyl
`carbitols such as methyl carbitol.
`
`3
`
`FlatWing Ex. 1047, p. 4
`
`
`
`Declaration of Stephen Kahl, Ph.D
`
`(Ex. 1007, Austin at 8:32–38.) Dr. Reider’s description of the nail as having
`
`“relatively high level of water content” (IPR2018-00168, Ex. 2013, ¶ 41;
`
`IPR2018-00169, Ex. 2013, ¶ 44; IPR2018-00170, Ex. 2013, ¶ 45; IPR2018-00171,
`
`Ex. 2013, ¶ 39) suggests that a POSA would read Austin, in combination with the
`
`other references cited, as providing a reasonable expectation of success that
`
`tavaborole could indeed be formulated for use in on the nail, including at a
`
`percentage solution such as 5% which could be determined by a routine dose
`
`ranging study as described by Dr. Murthy.
`
`*
`
`*
`
`*
`
`As provided in 28 U.S.C. § 1760, I declare under penalty of perjury that the
`
`foregoing is true and correct.
`
`Executed on: December __(cid:25)___, 2018 By:_______________________________
`____________________
`
`4
`
`FlatWing Ex. 1047, p. 5
`
`
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