IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In re application of
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`Masayo HIGASHIYAMA
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`Serial No. 10/500,354
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`Filed June 30, 2004
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`AQUEOUS LIQUID PREPARATIONS AND :
`LIGHT-STABILIZED AQUEOUS LIQUID
`PREPARATIONS
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`Attorney Docket No. 2004-_10I6A
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`Confirmation No. 2612
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`Group Art Unit 1611
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`Examiner Barbara S. Frazier
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`Mail Stop: AMENDMENT
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`DECLARATION UNDER 37 CFR 1.132
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`Commissioner for Patents
`P.O. Box 1450
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`Alexandria, VA 22313 - 1450
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`Sm
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`I, Masayo HIGASHIYAMA, the undersigned, a citizen ofJapan, residing at Suita-shi,
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`Osaka, Japan, do hereby declare:
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`I.
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`2.
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`I am the sole inventor of the above—identified application.
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`I
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`I graduated from Nagoya City University, Japan, Graduate School of
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`Pharmaceutical Sciences, in March 1995, and received a Doctor’s degree in Engineering from
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`Kyushu Institute of Technology, Japan, in September 2007.
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`3.
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`Since April 1995 up to this time, I have been an employee of Senju
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`Pharmaceutical Co., Ltd., and engaged in the pharmaceutical research of ophthalinic formulation.
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`4.
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`I have reviewed the Office Action dated November 30, 201 1, the Advisory Action
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`dated May 2, 2012 and the Interview Summary dated July 2, 2012, and the references cited
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`therein, in the above-idcntificd U.S. Application Serial No. 10/500,354.
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`5.
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`I declare the following distinctions between the invention claimed in the above-
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`identified application and the following references: Kita et al. (U.S. Patent No. 6,307,052),
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`Lehmussaari et ai. (U.S. Patent No. 5,795,913) and Araki et al. (US. Patent Application
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`Publication No. 2003/0139436).
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`The Distinctions Between the Claimed Invention and the Cited References
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`I.
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`Carbogol Would Materially Affect the Basic and
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`Novel Characteristics of the Claimed Invention
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`The Examiner has combined Kita et a1., disclosing (+)-(S)-4-[4—[(4-chlorophenyl)(2-
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`pyridyl)methoxy]piperidino] butyric acid (hereinafter, “bepotastine”), with Lehmussaari et al.,
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`disclosing a metal chloride, to arrive at the claimed invention.
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`Claims 1, 101 and 13 of the present application recite the transitional phrase “consisting
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`essentially of”, which limits the scope of a claim to the specified materials or steps and those that
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`do not materially affect the bag and J characteristic(s) of the claimed invention (see MPEP
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`21 11.03).
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`The composition of Lehmussaari et al. requires the inclusion of an ion sensitive,
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`hydrophilic polymer having viscosity, such as Carbopol, to control the formation of the polymer
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`film on the cornea of the eye, and each of the reference’s examples contain Carbopol (please see
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`col. 2, line 57 to col. 3, line 6, and the Examples).
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`Carbopol is degraded by light. This is clear from the Chemical Abstract reference dated
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`January 3, 1972 enclosed with the Amendment filed April 24, 2012. The reference is submitted
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`again herewith in an Information Disclosure Statement. The reference states
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`“CARBOXYVINYL POLYIVEERS of the type Carbopol 940. . .and 941 were degraded by light,
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`type 941 presenting the highest DEGRADATION” (emphasis in original). This clearly teaches
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`that it was known that Carbopol is degraded by light well—prior to the U.S. filing date of the
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`present application (2003).
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`Using an ion sensitive, hydrophilic polymer, such as Carbopol, in the aqueous liquid
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`preparation of claim 1 and the eye drops of claims 10 and 13 would materially affect the basic,
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`and Lel characteristics of the claimed compositions, because it would introduce a component
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`that degrades in light into a composition that is designed to be “light-stabilized” by a water-
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`solubie metal chloride.
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`As a result, an ion sensitive, hydrophilic polymer is excluded from the aqueous liquid
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`preparation of claim 1 and the eye drops of claims 10 and 13. Therefore, a person of ordinary
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`1 Claim 10 will be amended to recite “consisting essentially of” when this Declaration is filed in the USPTO.
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`MYLAN Ex. 1027, Page2
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`skill in the art could not have arrived at the presently claimed invention from the combination of
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`Kita et al., disclosing bepotastine, and Lehmussaari et al., disclosing a metal chloride in a
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`composition with Carbopol, with any reasonable expectation of success.
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`II.
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`Araki et al.
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`A.
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`The Differences Between Bepotastine and Sitafloxacin
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`Araki et al. disclose a composition comprising sitafloxacin (see abstract). Sitafloxacin
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`has a completely different chemical structure and has completely different chemical properties as
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`compared to bepotastine, which is contained in the claimed compositions.
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`Sitafloxacin has the following chemical structure:
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`F
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`COOH
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`The compounds clearly have different chemical structures, and virtually no similar
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`chemical moieties. For example, sitafloxacin has an oxoquinoline core bonded to a cyclopropyl
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`group and a azaspiro[2,4]heptan group. On the other hand, bepotastine does not have any
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`bicyclic or spiro rings, and has separate pyridine and piperidine rings. There are no common
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`chemical groups in the two compounds that would suggest they share any similar activity or have
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`any similar properties.
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`Araki et al. disclose light stabilization of sitafloxacin by sodium chloride. Sodium
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`chloride is generally used for isotonization.
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`Since sitafloxacin has a completely different chemical structure and completely different
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`3
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`MYLAN Ex. 1027, Page3
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`chemical properties as compared to bepotastine, as discussed above, there is no predictability or
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`correlation of light stabilization of bepotastine by sodium chloride.
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`Therefore, one skilled in the art would not expect a metal chloride to have a light-
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`stabilizing effect on bepostatine in view of the iight stabilizing effect of sodium chloride on
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`sitafloxacin.
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`B.
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`There is No Reasonable Exgectation that Sodium Chloride Would
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`Suppress Coloration and Precipitation of Begotastine in view ofAraki et al.
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`Araki et al. state the following:
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`[0100] As is understood from Table l, the aqueous sitafioxacin solutions without sodium
`chloride or containing D-sorbitol in place of sodium chloride undergo reductions in pH,
`transmission and sitafloxacin content and an increase of related substances when
`irradiated.
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`[0101] However, it is apparent that addition of sodium chloride suppresses these
`unfavorable changes due to irradiation, showing improvement on sitafloxacin stability
`against light.
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`The reference is silent on the suppression of coloration and precipitation. While Araki et
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`al. teach that the addition of sodium chloride results in the suppression of changes in
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`transmission, the reference does not teach or suggest that sodium chloride causes coloration, and,
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`likewise, does not mention the suppression of coloration by sodium chloride.
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`On the other hand, the present application demonstrates that when an aqueous bepotastine
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`solution free of sodium chloride was subjected to light irradiation, the solution turned black
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`green, and a precipitate was produced (see specification, page 8, lines 8-9, Formulation 1). A
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`person of ordinary skill in the art with the goal of reducing or eliminating this phenomenon
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`would not refer to the teachings Araki et al. and would not have been motivated by the teachings
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`to Araki et al. to include a metal chloride in a bepotastine composition, because the reference
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`provides no description regarding coloration and precipitation.
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`Accordingly, there would have been no reasonable expectation of success of arriving at
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`the claimed invention from the disclosure of Araki et al.
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`Therefore, the aqueous liquid preparation of claim 1 and the eye drops of claims 10 and
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`13 would not have been obvious over Araki et al. in view of Kita et al. and/or Lehmussaari et al.,
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`or in view of any other reference.
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`MYLAN Ex. 1027, Page4
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`I further declare that all statements made herein of my own knowledge are true and all
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`statements made on information and belief are believed to be true; and further that these
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`statements were made with the knowledge that willful false statements and the like so made are
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`punishable by fine or imprisonment, or both, under Section 1001 of Title 18 of the United States
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`Code and that such willful false statements may jeopardize the Validity of this application or any
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`patent issuing thereon.
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`Signed at ,é(2L , Japan on this / /7/1 day of September, 2012
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`Masayo HIGASHIYAIVLA
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`MYLAN EX. 1027, Page5
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`MYLAN Ex. 1027, Page5