`
`UNITED STATES DEPARTMENT OF COMMERCE
`United Slalcs Patent! and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Bax: I450
`Alcxiumrizu. \u"irgim'u 22.lI.‘- I450
`www.uspm.gov
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`APPLICATION NO.
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`I
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`FILING DATE.
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`FIRST NAMED INVENTOR
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`ATTORNEY DOCKET NO.
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`CONFIRMATION NO.
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`l0J'Sl]0,354
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`l)6f3flJ'2004
`
`Masayo Higashiyama
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`-
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`20fl4_l0 IGA
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`26l2
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`5 I3
`1590
`02.I"0fir‘2|J0R
`WENDEROTH,L1'ND&PONACK,L.L.P.
`K
`EVUI§S1§Ig2iT0N DC zeooe- I 021
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`RAE, CHARLESWORTH E
`W “N”
`"“"E"* "‘””B“’*
`[fall
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`MAIL DATE
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`{IZIOBIZOOR
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`DELIVERY MODE
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`PAPER
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`' Please find below _and:’or attached an Office communication concerning this application or proceeding.
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`The time period for reply, if any, is set in the attached communication.
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`PTOL-90A (Rev. 04107)
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`MYLAN EX. 1021, Page1
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`MYLAN Ex. 1021, Page1
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`Office Action Summary
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`Applicantlsl
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`Application No.
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`HIGASHIYAMA, MASAYO
`Examine,$1
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`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address -
`Period for Reply
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`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 |’v‘|ONTH(S) OR THIRTY (30) DAYS.
`WHICHEVER IS LONGER. FROM THE MAILING DATE OF THIS COMMUNICATION.
`- Extensions of lime may be available under the provisions ol 3? CFR 1.13B(a).
`In no event. however. may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`It NO period tot reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS trom the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute. cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date oi this communication. even if timely filed. may reduce any
`earned patent tenn adjustment See 3? CFR 1.70-uh}.
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`Status
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`1}® Responsive to cornmunicalion(s) filed on 11/13/07.
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`2a)E This action is FINAL.
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`2b)I:I This action is non-final.
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`3)I:| Since this application is in condition for allowance except for format matters, prosecution as to the merits is
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`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
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`Disposition of Claims
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`4)IZ Claim(s) 1 isiare pending in the application.
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`4a) Of the above claim(s) fl isiare withdrawn from consideration.
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`5)I:] Claim(s) j islare allowed.
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`6)IX| Claim(s) _‘ij_-_1_t_)' isfare rejected.
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`7)|:| Claim(s) __ isiare objected to.
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`8)I:| Claim(s) _ are subject to restriction and.-‘or election requirement.
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`Application Papers
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`9)I:l The specification is objected to by the Examiner.
`10)!:] The drawing(s) filed on j isiarer a)I:I accepted or b)I:I objected to by the Examiner.
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`Applicant may not request that any objection to the drawing(s) be held in abeyanoe. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).
`I 11)EI The oath or declaration is objected to by the Examiner. Note the attached Office Action or fonn PTO—152.
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`Priority under 35 U.S.C. § 119
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`12)l:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
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`ail] All
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`b)I:j Some * c)I:| None of:
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`1.I:| Certified copies of the priority documents have been received.
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`2.I:| Certified copies of the priority documents have been received in Application No. _
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`3.l:I Copies of the certified copies of the priority documents have been received in this National Stag
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`application from the international Bureau (PCT Rule 17.2(a)).
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`'
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`* See the attached detailed Office action for a list of the certified copies not received.
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`Attachmenttsj
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`4) I] Interview Summary u=-'ro—413)
`PBPEF N0(5}-‘Mail Data __
`5) El N°“°e Of '"f°|‘m=' Patent Animation
`6) El Other: _.
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`1) IX] Notice of References Cited (PTO-892)
`2) El Notice of Draltsperson's Patent Drawing Review (PTO-948}
`3} El Information Disclosure Stalernent(s) (PTOr‘SBi‘03)
`Paper No(s)!Mail Date
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`US. Patent and Trademark Oflice
`PTOL-326 (Rev. 03-06)
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`Office Action Summary
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`Part of Paper Hm-‘Mail Date 20071018
`MYLAN EX. 1021, Page2
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`MYLAN Ex. 1021, Page2
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`I Applicationlcontrol Number: 101500354
`Art Unit: 1611
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`Page 2
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`DETAILED ACTION
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`Applicant’s argumentslarnendment, filed 1019107, and supplemental
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`responselamendment, filed 11113‘/O7, have been fully considered but they are not
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`' deemed to be persuasive. Rejections and/or objections not reiterated from
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`previous office actions are hereby withdrawn. The following rejections andfor
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`I objections are either reiterated or newly applied. They constitute the complete set
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`of actions being applied to the instant application.
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`Entry of the amendment to the specification, filed 10l09:‘07, is hereby
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`granted. No new matter is deemed to have been introduced by the said
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`amendment (see amendment).
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`Applicant's statement that Formulation 7 discloses monobenzenesulfonate
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`as “bepotastine besilate (Table 2 and specification at page 1, lines 25-27) is
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`acknowledged.
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`This action is made final.
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`Status of the Claims
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`Claims 1-11 are currently pending in this application.
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`Ctaim 11 is withdrawn for being directed to non-elected subject matter.
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`Claims 1-10 are under examination.
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`Claim of Priority
`Receipt of a non-English certified copy of the Foreign Priority application
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`received 6130104 is acknowledged and made of record. The effective filing date of
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`the instant application is considered to be July 30, 2003, which is the filing date
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`of the international application PCTlJP03l0971 3. Applicant is invited to submit
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`MYLAN EX. 1021, Page3
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`MYLAN Ex. 1021, Page3
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`Applicationlcontrol Number: 10i'500,354
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`- Art Unit: 1611
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`Page 3
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`an English translation of the priority document in support of the claimed benefit to
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`the filing date of the foreign priority document (i.e. July 31, 2002).
`Declaration
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`The declaration of Dr. Higasiyama, filed 11I13!07, under CFR 1.32 is
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`acknowledged. The experimental data provided showing the light-stabilizing
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`effect of water—soluble metal chloride bepotastine besilate aqueous solutions as
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`disclosed in Examples 1-4 are appreciated. Dr. Higasiyama’s conclusion
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`statement that the "results indicate that water-soluble metal chloride improves
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`light-stability of bepotastine besilate and that isotonic agents such as glycerin,
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`saccharides and the light do not improve light-stability of bepotastine besilate" is
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`found to be applicable only to non-metal chloride isotonic agents such as glycerin
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`and saccharides. The data fail to reasonably address the fact that, unlike the
`non-ionizable non-alkali metal isotonic agents (e.g. glycerin) disclosed by Dr.
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`Higasiyama, the isotonic property of the "claimed ionizable alkali metal chlorides
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`(e.g. sodium chloride) when employed in pharmaceutical aqueous solutions e.g.
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`eyefnasal solutions-, is coextensive with the purported claimed light-stabilizing
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`property of said metal chlorides. To the extent that the instant claims encompass
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`metal chloride isotonic agents, as oppose to glycerinlsaccharide isotonic agents,
`the declaratory evidence is not commensurate in scope with the instant claims.
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`Thus, the declaration is found to be insufficient to overcome the rejection of
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`record.
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`Obiection
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`Response to applicant's argumentsfremarks
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`MYLAN EX. 1021, Page4
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`MYLAN Ex. 1021, Page4
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`ApplicationlContro| Number: 101500354
`Art Unit: 1611
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`Page 4
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`The objection to the specification is withdrawn in view of the amendment
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`to the specification filed 10!09i'07_
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`Rejection under 103(a)
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`Applicant asserts that this rejection should be withdrawn "for the flowing
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`reasons:
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`1) Koicla et al. and Kita et al. do not disclose or suggest-an aqueous
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`solution containing a pharmacologically acceptable acid addition salt of
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`bepotastine, and metal chloride, and a light-stabilization method of an aqueous
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`solution containing bepotastine.
`2) Remingtonls teach calcium chloride, potassium chloride or sodium
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`chloride are generally used for isotonization, but do not teach the use of these
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`agents to light stabilize a drug in aqueous solution as claimed in the instant
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`application.
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`3) The comparative test results employing the isotonic agents, glycerin,
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`glucose, and mannitol, clearly show that the light stabilizing effect of the present
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`invention is not an effect accompanyinglisotonization. The finding of the metal
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`chloride light‘-stabilizing effect was an unexpected finding and therefore the
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`combination of references donot render the instant claimed invention obvious.
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`In response, the rejection is maintained as applicant’s arguments are not
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`found to be persuasive for the reasons previously made of record in the Office
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`action mailed 7i‘9l07 and for the additional following reasons:
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`MYLAN EX. 1021, Page5
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`MYLAN Ex. 1021, Page5
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`‘Application/Control Number: 10500354
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`Art Unit: 1611
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`Page 5
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`1) Metal chlorides are routinely employed as isotonic agents as evidenced
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`by Remington's. An artisan skilled in the art would reasonably envisage the use
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`of these metal_chloride "isotonic agents" in water—based solutions i.e. aqueous
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`solutions. Besides, the instant invention encompasses eye drops (see claim 8),
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`which are known in the art to comprise metal chlorides such as ‘sodium chloride
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`as evidenced by the teaching of Asgharian of an eye drop containing 0.5 % wlv
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`of sodium chloride (US Patent 6,403,609; col. 7, Example 2). Further, the instant
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`claimed amounts of metal chlorides recited in claims 2 and 10 are considered to
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`constitute optimization which is within the scope of skill and knowledge of an
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`artisan skilled in the art via routine experimentation (see also Table 1 of Dr.
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`Higasiyama declaration, filed 11113107, showing sodium chloride in amounts of
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`0.1 g, Example 3, 0.3 g, Example 4, and 0.6 g, Example 7; potassium chloride is
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`0.79 ,Example 5; and calcium chloride is 1.8 g, Example 6
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`2).
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`2) Eye drops and nasal drops containing ant-histamines are knownin the
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`art as evidenced by the teaching of Mito et at. (English abstract only).
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`3) The identification of a new property of metal chlorides do not render the
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`claimed composition patentable as these agents are used in aqueous solutions
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`I. within the same concentrations.
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`4) Thus, someone of skill in the art would have deemed it obvious to
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`combine the cited reference teachings to create albeit an isotonic aqueous eye or
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`nasal solution comprising the claimed antihistamine, bepotastine besilate, and a
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`metal chloride with a pH in the range of 4-8.5, for treating allergic rhinitis.
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`MYLAN EX. 1021, Page6
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`MYLAN Ex. 1021, Page6
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`Applicationicontrol Number: 10/500,354
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`Page 6
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`Art Unit: 1611
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`Claim rejections — 35 USC 103(a)
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`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for
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`all obviousness rejections set forth in this Office action:
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`(a) A patent may not be obtained though the invention is not identically disclosed or described
`as set forth in section 102 01' this title, if the differences between the subject matter sought to
`be patented and the prior art are such that the subject matter as a whole would have been
`obvious at the time the invention was made to a person having ordinary skill in the art to which
`said subject matter pertains. Patentability shall not be negalived by the manner in which the
`invention was made.
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`This application currently names joint inventors.
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`in considering -
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`patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that
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`the subject matter of the various claims was commonly owned at the time any
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`inventions covered therein were made absent any evidence to the contrary.
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`Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor
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`and invention dates of each claim that was not commonly owned at the time a
`later invention was made in order for the examiner to consider the applicability of
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`35 U.S.C. 103(a) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35
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`U.S.C. 103(a).
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`Claims 1-10 are rejected under 103(a) as being unpatentable over Koida
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`et al. (JP 2001261553A, abstract only), in view of Kita et al (US Patent 6,307,052
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`B1), and further in view of Remington’s (Remington’s Pharmaceutical Sciences.
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`_ 1930; pages 1410-1419).
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`The above discussion" of the rejection under 103(a) in connection with the
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`Response to applicant's argumentsirernarks is incorporated by reference.
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`Koida et al. teach bepotastine( i.e. .(S)-4-[4—[(4-chlorophenyl)(2-
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`pyridyl)methoxy]piperidino] butyric acid) has optical purity and has markedly
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`MYLAN EX. 1021, Page?
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`MYLAN Ex. 1021, Page7
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`ApplicationlControl Number: 10i'500,354
`Art Unit: 1611
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`Page 7
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`improved storage stability because of no occurrence of raoemization (abstract).
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`Claims 1, 4, 5, and 10 recite said compound.
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`Kita et al. teach benzenesulfonate and benzoate of '(S)—4—[4-[(4-
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`chlorophenyl)(2-pyridyl)methoxy]piperidino]butanoic acid possesses excellent
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`antihistaminic and antiallergic agent activity (column 1, line 10 to column 3, line
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`19). Kita et al. teach that the acid addition salt has little hydroscopicity and
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`excellent physiochemical stability so that it is particularly suitablencompound as a
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`medicine for allergic skin diseases, allergic rhinitis, sneeze, mucus, cough due to
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`respiratory inflammation such as a cold, and bronchial asthma (column ‘I,
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`lin'es11-54).
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`Remington’s Pharmaceutical Sciences (1980) teach sodium chloride
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`eguivalents of certain medicinals in agueous solution (pages 1411, column 2, to
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`1419; Appendix A), which includes calcium chloride (page 1413), potassium
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`chloride (page 1417), sodium chloride (page 1418), benzalkonium chloride
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`(page 1413). Remington’s also teaches the amount of water needed for
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`isotonicity (page 1419, Appendix B), for example, calcium chloride, potassium
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`chloride, and sodium chloride. Rernington’s teaches that besides water, certain
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`other solvents are frequently employed in nose drops, ear drops, and other
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`preparations to be used in various parts of the body (page 1410, column 2, '
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`second paragraph from the bottom); this teaching is reasonably construed to
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`include, for example, eye drops. Based on the teaching of Remington’s,
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`the
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`instant recited —cIaim limitations (e.g. metal chloride concentration of 0.15-1 .5
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`wIv%; acid addition salt concentration of 0.1-2 wlv%; pH 4-8.5; (S)-4-[4-[(4-
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`MYLAN EX. 1021, Page8
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`MYLAN Ex. 1021, Page8
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`Applicationlcontrol Number: 10l500,354
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`Page 8
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`Art Unit: 1611
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`chlorophenyl)(2-pyridy|)methoxy]piperidino] butyric acid monobenzenesulfonate
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`and sodium chloride at not less than 0.2 wlv% and not more than 0.8 wlv%) are
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`reasonably construed to be within the scope and skill of an artisan as these‘
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`limitations represent optimization of the pharmaceutical properties of the
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`composition.
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`I
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`Based on the teaching of Kita et al. that benzenesulfonate and benzoate
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`of (S)—4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butanoic acid
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`possesses excellent antihistaminic and antiallergic agent activity, and are
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`particularly suitable as a medicine for conditions such as allergic rhinitis (column
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`1, iine 10-54), someone of skill in the art at the time the instant invention was
`made would have been motivated to combine the teaching of Koida et al. (JP
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`2001261553A, abstract only), in view of Kita et al (US Patent 6,307,052 B1), and
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`further in view of Remington’s (Remington's Pharmaceutical Sciences. 1980;
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`pages 1410-1419) to create the instant inventive concept.
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`Thus, someone of skill in the art at the time the instant invention was
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`created would have deemed it obvious to create the instant claimed invention
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`with a reasonable predictability.
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`Relevant Art of Record
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`The below art reference made of record and relied upon is considered pertinent-'
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`to app|icant’S invention.
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`Onuki et al. (US Patent Application Pub. No. 2004l'0147605) teach
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`formulations comprising one or more antihistamine compound, including P
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`bepotastine besilate (page 2, para 001?, line 11).
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`.
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`MYLAN EX. 1021, Page9
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`MYLAN Ex. 1021, Page9
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`Applicationlcontrol Number: 10l500,354
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`Page 9
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`Art Unit: 1611
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`Himmelstein et al. (US Patent'5,599,534) teach pH-responsive reversible
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`gelling compositions and liquid fonnulations for sustained delivery of therapeutic
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`or diagnostic _agents suitable for use as drop or spray instillable or topical drug
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`delivery vehicles for drugs various drugs, including antihistamines and
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`decongestants (e.g. pyrilmaine, chlorpheniramine, tetrahydrazoline, antazonline),
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`which are particularly suitable for delivering pharmaceutical compounds to the
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`ocular environment due to clarity and lubricating properties of the gel (col. 5,
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`lines 32-49 and col. 8, line 51 to col. 9, line 9); flowable liquid forms of the
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`composition are particularly useful for pharmaceutical formulations to be applied
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`by drops (e.g. eye drops) or sprays (e.g. nasal sprays). See col. 7, lines 49-59;
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`and col. 8, lines 29-34. Himmelstein et al. teach thatnthe pH preferably is within
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`the physiological range between pH 2.5 and 7.5 (col. 6, lines 35-39).
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`THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is
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`reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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`A shortened statutory period for reply to this final action is set to expire
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`THREE MONTHS from the mailing date of this action.
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`In the event a first reply is
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`filed within TWO MONTHS of the mailing date of this final action and the advisory
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`action is not mailed until after the end of the THREE-MONTH shortened statutory
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`period, then the shortened statutory period will expire on the date the advisory-
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`action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be
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`calculated from the mailing date of the advisory action.
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`In no event, however, will
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`'
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`the statutory period for reply expire later than SIX MONTHS from-thedate of this '
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`final action.
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`MYLAN EX. 1021, Page’l0
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`MYLAN Ex. 1021, Page10
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`Applicationlcontrol Number: 10500354
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`Art Unit: 1611
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`Page 10
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`Any inquiry concerning this communication or earlier communications from
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`the examiner should be directed to Charlesworth Rae whose telephone number
`is 571-272-6029. The examiner can normally be reached between 9 a.m. to 5:30 I
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`p.m. Monday to Friday.
`I
`I
`If attempts to reach the examiner by telephone are unsuccessful, the
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`examiners supervisor, Michael Woodward, can be reached at 571-272-8373.
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`The fax phone number for the organization where this application or proceeding
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`is assigned is 571-273-8300.
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`I
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`Information regarding the status of an application may be obtained from
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`the Patent Application Information Retrieval (PAIR) system. Status information
`for published applications. may be obtained from either Private PAlR or Public
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`PAIR.
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`Status information for unpublished applications is available through
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`Private PAIR only. For more information about the PAIR system, see http:pair-
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`direct.uspto.gov. Should you have any questions on access to the Private PAIR
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`system, contact the Electronic Business Center (EBC) at 800-217-9197 (toll-
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`free).
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`If you would like assistance from a-USPTO Customer Service
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`I
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`Representative or access to the automated information system, call 800-788-
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`9199 (IN USA OR CANADA) or 571-272-1000.
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`27 January 2008
`CER
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`, Ne. 8.1-(WON
`B:I;?t‘:A\‘,§{ EXAMINER
`5fl’~“/“’L”’”’
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`MYLAN EX. 1021, Page11
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`MYLAN Ex. 1021, Page11