UNITED STATES PATENT AND TRADEMARK OFFICE
`
`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
`
`APPLICATION NO.
`
`I
`
`FILING DATE.
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`l0J'Sl]0,354
`
`l)6f3flJ'2004
`
`Masayo Higashiyama
`
`-
`
`20fl4_l0 IGA
`
`26l2
`
`5 I3
`1590
`02.I"0fir‘2|J0R
`WENDEROTH,L1'ND&PONACK,L.L.P.
`K
`EVUI§S1§Ig2iT0N DC zeooe- I 021
`
`RAE, CHARLESWORTH E
`W “N”
`"“"E"* "‘””B“’*
`[fall
`
`MAIL DATE
`
`{IZIOBIZOOR
`
`DELIVERY MODE
`
`PAPER
`
`' Please find below _and:’or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`r
`
`PTOL-90A (Rev. 04107)
`
`
`
`MYLAN EX. 1021, Page1
`
`MYLAN Ex. 1021, Page1
`
`

`
`Office Action Summary
`
`Applicantlsl
`
`Application No.
`
`HIGASHIYAMA, MASAYO
`Examine,$1
`
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address -
`Period for Reply
`
`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}.
`
`Status
`
`1}® Responsive to cornmunicalion(s) filed on 11/13/07.
`
`2a)E This action is FINAL.
`
`2b)I:I This action is non-final.
`
`3)I:| Since this application is in condition for allowance except for format matters, prosecution as to the merits is
`
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`4)IZ Claim(s) 1 isiare pending in the application.
`
`4a) Of the above claim(s) fl isiare withdrawn from consideration.
`
`5)I:] Claim(s) j islare allowed.
`
`6)IX| Claim(s) _‘ij_-_1_t_)' isfare rejected.
`
`7)|:| Claim(s) __ isiare objected to.
`
`8)I:| Claim(s) _ are subject to restriction and.-‘or election requirement.
`
`Application Papers
`
`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.
`
`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.
`
`Priority under 35 U.S.C. § 119
`
`12)l:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`
`ail] All
`
`b)I:j Some * c)I:| None of:
`
`1.I:| Certified copies of the priority documents have been received.
`
`2.I:| Certified copies of the priority documents have been received in Application No. _
`
`3.l:I Copies of the certified copies of the priority documents have been received in this National Stag
`
`application from the international Bureau (PCT Rule 17.2(a)).
`
`'
`
`* See the attached detailed Office action for a list of the certified copies not received.
`
`Attachmenttsj
`
`4) I] Interview Summary u=-'ro—413)
`PBPEF N0(5}-‘Mail Data __
`5) El N°“°e Of '"f°|‘m=' Patent Animation
`6) El Other: _.
`
`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
`.
`US. Patent and Trademark Oflice
`PTOL-326 (Rev. 03-06)
`
`Office Action Summary
`
`Part of Paper Hm-‘Mail Date 20071018
`MYLAN EX. 1021, Page2
`
`MYLAN Ex. 1021, Page2
`
`

`
`I Applicationlcontrol Number: 101500354
`Art Unit: 1611
`
`Page 2
`
`DETAILED ACTION
`
`Applicant’s argumentslarnendment, filed 1019107, and supplemental
`
`responselamendment, filed 11113‘/O7, have been fully considered but they are not
`
`' deemed to be persuasive. Rejections and/or objections not reiterated from
`
`previous office actions are hereby withdrawn. The following rejections andfor
`
`I objections are either reiterated or newly applied. They constitute the complete set
`
`of actions being applied to the instant application.
`
`Entry of the amendment to the specification, filed 10l09:‘07, is hereby
`
`granted. No new matter is deemed to have been introduced by the said
`
`amendment (see amendment).
`
`Applicant's statement that Formulation 7 discloses monobenzenesulfonate
`
`as “bepotastine besilate (Table 2 and specification at page 1, lines 25-27) is
`
`acknowledged.
`
`This action is made final.
`
`Status of the Claims
`
`Claims 1-11 are currently pending in this application.
`
`Ctaim 11 is withdrawn for being directed to non-elected subject matter.
`
`Claims 1-10 are under examination.
`
`Claim of Priority
`Receipt of a non-English certified copy of the Foreign Priority application
`
`received 6130104 is acknowledged and made of record. The effective filing date of
`
`the instant application is considered to be July 30, 2003, which is the filing date
`
`of the international application PCTlJP03l0971 3. Applicant is invited to submit
`
`MYLAN EX. 1021, Page3
`
`MYLAN Ex. 1021, Page3
`
`

`
`Applicationlcontrol Number: 10i'500,354
`
`- Art Unit: 1611
`
`'
`
`Page 3
`
`an English translation of the priority document in support of the claimed benefit to
`
`the filing date of the foreign priority document (i.e. July 31, 2002).
`Declaration
`
`The declaration of Dr. Higasiyama, filed 11I13!07, under CFR 1.32 is
`
`acknowledged. The experimental data provided showing the light-stabilizing
`
`effect of water—soluble metal chloride bepotastine besilate aqueous solutions as
`
`disclosed in Examples 1-4 are appreciated. Dr. Higasiyama’s conclusion
`
`statement that the "results indicate that water-soluble metal chloride improves
`
`light-stability of bepotastine besilate and that isotonic agents such as glycerin,
`
`saccharides and the light do not improve light-stability of bepotastine besilate" is
`
`found to be applicable only to non-metal chloride isotonic agents such as glycerin
`
`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.
`
`Higasiyama, the isotonic property of the "claimed ionizable alkali metal chlorides
`
`(e.g. sodium chloride) when employed in pharmaceutical aqueous solutions e.g.
`
`eyefnasal solutions-, is coextensive with the purported claimed light-stabilizing
`
`property of said metal chlorides. To the extent that the instant claims encompass
`
`metal chloride isotonic agents, as oppose to glycerinlsaccharide isotonic agents,
`the declaratory evidence is not commensurate in scope with the instant claims.
`
`Thus, the declaration is found to be insufficient to overcome the rejection of
`
`record.
`
`Obiection
`
`Response to applicant's argumentsfremarks
`
`MYLAN EX. 1021, Page4
`
`MYLAN Ex. 1021, Page4
`
`

`
`ApplicationlContro| Number: 101500354
`Art Unit: 1611
`
`,
`
`I
`
`Page 4
`
`The objection to the specification is withdrawn in view of the amendment
`
`to the specification filed 10!09i'07_
`
`Rejection under 103(a)
`
`Applicant asserts that this rejection should be withdrawn "for the flowing
`
`reasons:
`
`1) Koicla et al. and Kita et al. do not disclose or suggest-an aqueous
`
`solution containing a pharmacologically acceptable acid addition salt of
`
`bepotastine, and metal chloride, and a light-stabilization method of an aqueous
`
`solution containing bepotastine.
`2) Remingtonls teach calcium chloride, potassium chloride or sodium
`
`chloride are generally used for isotonization, but do not teach the use of these
`
`agents to light stabilize a drug in aqueous solution as claimed in the instant
`
`application.
`
`3) The comparative test results employing the isotonic agents, glycerin,
`
`glucose, and mannitol, clearly show that the light stabilizing effect of the present
`
`invention is not an effect accompanyinglisotonization. The finding of the metal
`
`chloride light‘-stabilizing effect was an unexpected finding and therefore the
`
`combination of references donot render the instant claimed invention obvious.
`
`In response, the rejection is maintained as applicant’s arguments are not
`
`found to be persuasive for the reasons previously made of record in the Office
`
`action mailed 7i‘9l07 and for the additional following reasons:
`
`MYLAN EX. 1021, Page5
`
`MYLAN Ex. 1021, Page5
`
`

`
`‘Application/Control Number: 10500354
`
`Art Unit: 1611
`
`I
`
`Page 5
`
`1) Metal chlorides are routinely employed as isotonic agents as evidenced
`
`by Remington's. An artisan skilled in the art would reasonably envisage the use
`
`of these metal_chloride "isotonic agents" in water—based solutions i.e. aqueous
`
`solutions. Besides, the instant invention encompasses eye drops (see claim 8),
`
`which are known in the art to comprise metal chlorides such as ‘sodium chloride
`
`as evidenced by the teaching of Asgharian of an eye drop containing 0.5 % wlv
`
`of sodium chloride (US Patent 6,403,609; col. 7, Example 2). Further, the instant
`
`claimed amounts of metal chlorides recited in claims 2 and 10 are considered to
`
`constitute optimization which is within the scope of skill and knowledge of an
`
`artisan skilled in the art via routine experimentation (see also Table 1 of Dr.
`
`Higasiyama declaration, filed 11113107, showing sodium chloride in amounts of
`
`0.1 g, Example 3, 0.3 g, Example 4, and 0.6 g, Example 7; potassium chloride is
`
`0.79 ,Example 5; and calcium chloride is 1.8 g, Example 6
`
`2).
`
`2) Eye drops and nasal drops containing ant-histamines are knownin the
`
`art as evidenced by the teaching of Mito et at. (English abstract only).
`
`3) The identification of a new property of metal chlorides do not render the
`
`claimed composition patentable as these agents are used in aqueous solutions
`
`I. within the same concentrations.
`
`4) Thus, someone of skill in the art would have deemed it obvious to
`
`combine the cited reference teachings to create albeit an isotonic aqueous eye or
`
`nasal solution comprising the claimed antihistamine, bepotastine besilate, and a
`
`metal chloride with a pH in the range of 4-8.5, for treating allergic rhinitis.
`
`MYLAN EX. 1021, Page6
`
`MYLAN Ex. 1021, Page6
`
`

`
`Applicationicontrol Number: 10/500,354
`
`Page 6
`
`Art Unit: 1611
`
`Claim rejections — 35 USC 103(a)
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for
`
`all obviousness rejections set forth in this Office action:
`
`(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.
`'
`
`This application currently names joint inventors.
`
`in considering -
`
`patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that
`
`the subject matter of the various claims was commonly owned at the time any
`
`inventions covered therein were made absent any evidence to the contrary.
`
`Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor
`
`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
`
`35 U.S.C. 103(a) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35
`
`U.S.C. 103(a).
`
`Claims 1-10 are rejected under 103(a) as being unpatentable over Koida
`
`et al. (JP 2001261553A, abstract only), in view of Kita et al (US Patent 6,307,052
`
`B1), and further in view of Remington’s (Remington’s Pharmaceutical Sciences.
`
`_ 1930; pages 1410-1419).
`
`The above discussion" of the rejection under 103(a) in connection with the
`
`Response to applicant's argumentsirernarks is incorporated by reference.
`
`Koida et al. teach bepotastine( i.e. .(S)-4-[4—[(4-chlorophenyl)(2-
`
`pyridyl)methoxy]piperidino] butyric acid) has optical purity and has markedly
`
`MYLAN EX. 1021, Page?
`
`MYLAN Ex. 1021, Page7
`
`

`
`ApplicationlControl Number: 10i'500,354
`Art Unit: 1611
`'
`
`_
`
`Page 7
`
`improved storage stability because of no occurrence of raoemization (abstract).
`
`Claims 1, 4, 5, and 10 recite said compound.
`
`Kita et al. teach benzenesulfonate and benzoate of '(S)—4—[4-[(4-
`
`chlorophenyl)(2-pyridyl)methoxy]piperidino]butanoic acid possesses excellent
`
`antihistaminic and antiallergic agent activity (column 1, line 10 to column 3, line
`
`19). Kita et al. teach that the acid addition salt has little hydroscopicity and
`
`excellent physiochemical stability so that it is particularly suitablencompound as a
`
`medicine for allergic skin diseases, allergic rhinitis, sneeze, mucus, cough due to
`
`respiratory inflammation such as a cold, and bronchial asthma (column ‘I,
`
`lin'es11-54).
`
`Remington’s Pharmaceutical Sciences (1980) teach sodium chloride
`
`eguivalents of certain medicinals in agueous solution (pages 1411, column 2, to
`
`1419; Appendix A), which includes calcium chloride (page 1413), potassium
`
`chloride (page 1417), sodium chloride (page 1418), benzalkonium chloride
`
`(page 1413). Remington’s also teaches the amount of water needed for
`
`isotonicity (page 1419, Appendix B), for example, calcium chloride, potassium
`
`chloride, and sodium chloride. Rernington’s teaches that besides water, certain
`
`other solvents are frequently employed in nose drops, ear drops, and other
`
`preparations to be used in various parts of the body (page 1410, column 2, '
`
`second paragraph from the bottom); this teaching is reasonably construed to
`
`include, for example, eye drops. Based on the teaching of Remington’s,
`
`the
`
`instant recited —cIaim limitations (e.g. metal chloride concentration of 0.15-1 .5
`
`wIv%; acid addition salt concentration of 0.1-2 wlv%; pH 4-8.5; (S)-4-[4-[(4-
`
`MYLAN EX. 1021, Page8
`
`MYLAN Ex. 1021, Page8
`
`

`
`Applicationlcontrol Number: 10l500,354
`
`'
`
`Page 8
`
`Art Unit: 1611
`
`chlorophenyl)(2-pyridy|)methoxy]piperidino] butyric acid monobenzenesulfonate
`
`and sodium chloride at not less than 0.2 wlv% and not more than 0.8 wlv%) are
`
`reasonably construed to be within the scope and skill of an artisan as these‘
`
`limitations represent optimization of the pharmaceutical properties of the
`
`composition.
`
`I
`
`Based on the teaching of Kita et al. that benzenesulfonate and benzoate
`
`of (S)—4-[4-[(4-chlorophenyl)(2-pyridyl)methoxy]piperidino]butanoic acid
`
`possesses excellent antihistaminic and antiallergic agent activity, and are
`
`particularly suitable as a medicine for conditions such as allergic rhinitis (column
`
`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
`
`2001261553A, abstract only), in view of Kita et al (US Patent 6,307,052 B1), and
`
`further in view of Remington’s (Remington's Pharmaceutical Sciences. 1980;
`
`pages 1410-1419) to create the instant inventive concept.
`
`Thus, someone of skill in the art at the time the instant invention was
`
`created would have deemed it obvious to create the instant claimed invention
`
`with a reasonable predictability.
`
`Relevant Art of Record
`
`The below art reference made of record and relied upon is considered pertinent-'
`
`to app|icant’S invention.
`
`Onuki et al. (US Patent Application Pub. No. 2004l'0147605) teach
`
`formulations comprising one or more antihistamine compound, including P
`
`bepotastine besilate (page 2, para 001?, line 11).
`
`.
`
`MYLAN EX. 1021, Page9
`
`MYLAN Ex. 1021, Page9
`
`

`
`Applicationlcontrol Number: 10l500,354
`
`Page 9
`
`Art Unit: 1611
`
`Himmelstein et al. (US Patent'5,599,534) teach pH-responsive reversible
`
`gelling compositions and liquid fonnulations for sustained delivery of therapeutic
`
`or diagnostic _agents suitable for use as drop or spray instillable or topical drug
`
`delivery vehicles for drugs various drugs, including antihistamines and
`
`decongestants (e.g. pyrilmaine, chlorpheniramine, tetrahydrazoline, antazonline),
`
`which are particularly suitable for delivering pharmaceutical compounds to the
`
`ocular environment due to clarity and lubricating properties of the gel (col. 5,
`
`lines 32-49 and col. 8, line 51 to col. 9, line 9); flowable liquid forms of the
`
`composition are particularly useful for pharmaceutical formulations to be applied
`
`by drops (e.g. eye drops) or sprays (e.g. nasal sprays). See col. 7, lines 49-59;
`
`and col. 8, lines 29-34. Himmelstein et al. teach thatnthe pH preferably is within
`
`the physiological range between pH 2.5 and 7.5 (col. 6, lines 35-39).
`
`THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is
`
`reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
`
`A shortened statutory period for reply to this final action is set to expire
`
`THREE MONTHS from the mailing date of this action.
`
`In the event a first reply is
`
`filed within TWO MONTHS of the mailing date of this final action and the advisory
`
`action is not mailed until after the end of the THREE-MONTH shortened statutory
`
`period, then the shortened statutory period will expire on the date the advisory-
`
`action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be
`
`calculated from the mailing date of the advisory action.
`
`In no event, however, will
`
`'
`
`the statutory period for reply expire later than SIX MONTHS from-thedate of this '
`
`final action.
`
`MYLAN EX. 1021, Page’l0
`
`MYLAN Ex. 1021, Page10
`
`

`
`Applicationlcontrol Number: 10500354
`
`Art Unit: 1611
`
`'
`
`I‘
`
`_
`
`Page 10
`
`Any inquiry concerning this communication or earlier communications from
`
`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
`
`p.m. Monday to Friday.
`I
`I
`If attempts to reach the examiner by telephone are unsuccessful, the
`
`examiners supervisor, Michael Woodward, can be reached at 571-272-8373.
`
`The fax phone number for the organization where this application or proceeding
`
`is assigned is 571-273-8300.
`
`I
`
`Information regarding the status of an application may be obtained from
`
`the Patent Application Information Retrieval (PAIR) system. Status information
`for published applications. may be obtained from either Private PAlR or Public
`
`PAIR.
`
`Status information for unpublished applications is available through
`
`Private PAIR only. For more information about the PAIR system, see http:pair-
`
`direct.uspto.gov. Should you have any questions on access to the Private PAIR
`
`system, contact the Electronic Business Center (EBC) at 800-217-9197 (toll-
`
`free).
`
`If you would like assistance from a-USPTO Customer Service
`
`I
`
`Representative or access to the automated information system, call 800-788-
`
`9199 (IN USA OR CANADA) or 571-272-1000.
`
`27 January 2008
`CER
`
`, Ne. 8.1-(WON
`B:I;?t‘:A\‘,§{ EXAMINER
`5fl’~“/“’L”’”’
`
`MYLAN EX. 1021, Page11
`
`MYLAN Ex. 1021, Page11