‘I..Haw-20-03
`
`I
`
`02:23pm
`
`From-"TN. wane. zeuwo a snnnraan
`
`IN THE UNITED STA'I_'ES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`
`Beth A. BURNSIDE at al. _
`Serial No; 093801462
`Filed: July‘ 19, 2001
`
`Examiner: Russell Travers, Esq.
`Group An Unit; 1617
`BOX: AF
`
`793.”,
`
`
`For: ORAL PULSED DOSE DRUG DELIVERY SYSTEM
`
`ANIENDINIENT AFTER FINAL REJECTION
`
`E
`1
`
`1J
`
`.
`
`Assistant Commissioner for Patents
`Washington, DC. 20231
`
`Sir:
`
`The following is responsive to the Office Action of March 4, 2003.
`
`Amendments to me claims are reflected in the listing of claims which begins on page 2 of
`
`this paper.
`
`Remarksfikrgxunents begin on page S of this paper.
`
`1
`
`PHARNIA-142 P1
`
`Amerigen Ex. 1067, p. 1
`Amerigen Ex. 1067, p. 1
`
`

`
`{o Hay-20-U3
`
`‘
`
`02:23pm
`
`From-‘EN. WHITE. ZELANO & BRANIEAN
`
`TU
`
`10
`
`T-347
`
`p 13/2|]
`
`p-247
`
`-..—.
`
`
`
`This listing of claims will replace all prior versions, and listings. of claims in the application:
`
`[ASE0 of Claims:
`
`Claims 1-102 are canceled -
`
`103.
`
`(New) A p s . aceutical formulation for delivery of a mixture of amphetamine
`
`base salts eifective to treat AD. II in a human patient comprising:
`
`an immediate rele e dosage form that provides immediate release upon oral
`
`administration to said patient;
`
`a delayed enteric rel e dosage form that provides delayed release upon oral
`
`adnlinistration to said patient; and
`
`a pharmaceutically acc table carrier;
`
`wherein said arnphe =
`
`a ' e base salts comprise dextroamphetarnjne sulfate,
`
`dexiroamphetamine saccharate, amphe .- ' - - aspartate rnonohydrate and amphetamine sulfate;
`
`wherein said pliannaceutic: composition is sufiicient to maintain an effective
`
`level of amphetamine base salts in the pati - t over the course of at least 8 hours without further
`
`administration of amphetamine base salt, an the peak plasma concentration of amphetamine
`
`base salts reached after release of said delaye enteric release dosage form exceeds the peak
`
`plasma concentration previously reached after
`
`- lease of said immediate release dosage form;
`
`and
`
`wherein said pharmaceutical compotion produces in a human individual a
`
`plasma concentration versus time curve (ng/ml vers - hours) having an area under the curve
`
`(AUC) of about 467 to about 714 ng hr/ml, for about -. 20 mg total dose, or an AUC
`
`proportional thereto for a total dose other than about 2 mg.
`
`/
`(New) A formulation of claim 103 wherein aid plasma concentration curve has a
`
`104.
`
`maximum concentration (Cam) of about 22.5 to about 40 11 ml for about a 10 mg dose in each
`
`2
`
`Pl-IARMA-142 P I
`
`Amerigen Ex. 1067, p. 2
`Ame igen Ex. 1067, p. 2
`
`

`
`V May-zn-as
`
`uz:23pm
`
`From-wit. WHITE. 2ELANO&BRANlGAH
`
`703
`
`10
`
`1.347 mam am
`
`—-.._
`
`..
`
`X.
`\ Q)‘
`
`than about 10 mg.
`
`\
`.
`of said dosage forms, or a Cm”. pro ortional thereto for a dose in each of said dosage forms other
`
`(New) A formulation of claim 101 wherein the time after said oral administration
`
`105,
`
`to reach said Cum value is about 7 to about 10 hours.
`
`(New) A formulation o claim 193 wherein the time after said oral administration
`106.
`to reach maximum concentration of
`id plasma concentration curve is about 7 to about 10
`
`
`
`
`
`hours.
`
`hrfml.
`
`107.
`
`(New) A formulation of laim l0{10:'> or 106 wherein said ADC is about 714 ng
`
`
`
`\
`Q \
`
`(New) A formulation of cl ‘m 10{wherein said AUC is about 714 ng hrfml, the _
`103.
`time after said oral administration to reach aid Cm,“ value is about '7 hours and Cm,‘ is about 40
`
`(New) A formulation of clai
`
`I04 yvherein Cm.
`
`is about 40 ng/ml-
`
`
`
`109.
`
`1 10.
`
`(New) A formulation of claim 1 5/or 106 wherein said time is about 7 hours.
`
`( New) A formulation of one oft: a1'Jnsll03-106, 108 or 109 wherein said salts are
`11 1.
`contained in about equal amounts within each o said dosage forms and the total amphetamine
`
`salt amount in each of said dosage forms 13 abou the same.
`
`
`S’
`\@enteric release do sage form comprises at coa ing of
`
`(New) A formulation of on of cl
`
`'
`
`112.
`
`s 1133-106, 108 or 109 wherein said delayed
`
`thickness of at least 20 pm which
`
`C011-1pI'iSCS dried 30% (dry substance) aqueo
`
`
`
`methacrylic acid and acrylic acid ethyl ester, s
`
`U)
`
`
`
`ion of an anionic copolymcr based on
`
`‘ g being soluble at a pH of 5.5 upwards
`
`PH.AR.lV1A- 1 42 Pl
`
`Amerigen Ex. 1067, p. 3
`Amerigen Ex. 1067, p. 3
`
`

`
`M3l|'‘2U-'U3 U2:24PllI
`
`From-“EN. WHITE. ZELANU tic BRANIGKN
`
`.5
`
`.
`
`‘\
`
`700113
`
`T-34]?
`
`P 14/20
`
`[L247
`
`113.
`
`(New) A formulation of claim léwherein said thickness is at least 25 run.
`
`
`
`l 14.
`
`(New) A pharmaceutica1\’or1nularion for delivery ofa mixture ofamphetamine
`
`39/
`’ base salts effective to treat ADHD in a hymen patient comprising:
`
`an immediate release dosage form that provides immediate release upon oral administration to
`
`said patient;
`
`a delayed enteric release dosage to
`
`33
`
`that provides delayed release upon oral
`
`adrniriisrration to said patient, wherein said nteric release dosage form comprises a coating of a
`
`thickness of at least 20 pm which comprises
`
`‘ed 30% (dry substance) aqueous dispersion of an
`
`amonic copolyrner based on methacrylic acid and acrylic acid ethyl ester, said coating being
`
`soluble at a pH of5.5 upwards; and
`
`a pharmaceutically acceptable carrier;
`
`
`
`wherein said amphetamine base salts corn rise dcxtroamphetamine sulfate,
`
`dextroamphetamine saccharate, amphetamine aspartate rnonohydrate and arnphetai-nine sulfate;
`wherein said pharmaceutical composition is sufficient to maintain an effective level of /
`amphetamine base salts in the patient over the couzse of at least 8 hours without further
`administration of amphetarnine base salt, and the
`plasma concentration of amphetarnine
`base salts reached after release of said delayed enterx‘
`release dosage form exceeds the peak
`
`plasma concentration of said salts previously reached
`
`er release of said immediate release
`
`‘-
`
`dosage form.
`
`115.
`
`(New) A formulation of claim 11{wherein said thickness is at least 25 ;.u:o._
`
`i.
`
`11
`
`
`
`4
`
`-
`
`PI-IARNIA-1 42 P 1
`
`Amerigen Ex. 1067, p. 4
`Amerigen Ex. 1067, p. 4
`
`

`
`
`
`-:2
`
`'-‘-‘
`
`-1
`
`3
`
`M3!-2B-D3
`
`_
`
`a
`
`02:24pm . From-fill. WHITE. ZELAND & BRANIGAN
`
`703510
`
`T-E4?
`
`P_|5/2|]
`
`p-347
`
`;R_E+MA;R1£3_
`
`issues raised by the examiner are rendered moot by the foregoing. This is not to imply any
`
`agreement with any aspect of the office action. The previous claims met all requirements of 35
`
`U.S.C.
`
`Language in claims -1 09 and 11 1 regarding the enteric coating composition is based on
`
`conventional knowledge of the chemical composition of the enteric material utilized in Example
`2, i.e., EUDRAGIT ‘B L 30 13-55. Tlttis can be seen from the attached data sheets describing this
`
`well known enteric material, e.g., “EUDRAGIT L, Aqueous Dispersion, Data Sheet (lnfo LD-
`
`2ie). EUDRAGIT L 30 D” (two pages}, at page 1, top and column 1; and “EUDRAC‘rIT L,
`
`Aqueous Dispersion, Standards Sheet (info LD-7/e), EUDRAGIT I.__30 D” (two pages), at page
`
`1, top and columns 1 and 2. (The notation “S5” in the nomenclature used in the specification is
`
`an equivalent of the older nomenclature L 30 D, ‘'5?’ simply refemng to the pH (5.5) at which
`
`the enteric rnateiial becomes soluble.) Conventional values of area under the curve (AUC),
`
`maximum plasma concentration (Cmu) and the time to achieve Cmu, i.e., Tum, are taken directly
`
`from Figs. 7 and 8 of the application. Approximate AUC values were obtained by conventional
`
`weighing techniques and Cm,‘ and Tm,‘ by visual curve reading. The term "about” has its usual
`
`meaning in the field, e.g_, roughly 1 20%, for example as used by FDA in its deterrninatiorm of
`
`bioequivalency. The values from Figs. 7 and 8 are d-amphetamine levels to one of ordinary skill
`
`in the art. the mixture of ainphetatnine salts (“MAS" (page 1.6, lines 1546)) used in the examples
`
`being the "rnizmire of four atnphetarnine salts” in ADDERALIJE (page 4, lines 15-17) whose
`
`relative salt content is known. (See the PDR excerpts of record and the d—amphetarni_ne plasma
`
`curves in the prior art, e.g., in Sue et al_ also ofrecord.)
`
`Applicants maintain their position as set forth in the response submitted on October 24,
`
`2002. The cited prior art does not render obvious any of the previously pending claims or the
`claims being added at this time, for the reasons set forth in the mentioned amendment. Thus,
`there is nothing in the prior art which would motivate a skilled worker to formulate the claimed
`
`active ingredients in the manner recited in the claims. See the case law described in the last
`
`response. Moreover, the previous claims and the current claims meet all requirements of 35
`
`5
`
`PHARMA-142 P1
`
`Amerigen Ex. 1067, p. 5
`Amerigen Ex. 1067, p. 5
`
`

`
`
`
`May-2|]-D3
`
`02:24am
`
`Pretrial-__EN. WHITE. ZELANE! a BRANIGAN
`
`\
`
`7a‘m
`
`T-B4? ms/an
`
`F-247
`
`U.S.C. 1 12. The patent specification provides plentiful mformaxion whereby a skilled worker
`
`could, without undue experimentation, produce formulations which meet the requirements of the
`
`claims. e_g_, the plasma levels as defined previously or in the current claims.
`
`As for the comments of the E){¢'1l'I1L'1€1' on pages 4-6, the law has long been that
`
`functionality at the point of novelty is acceptable. In re Swtneharz, 439 F.2d 2} 0_ J 69 US P Q
`
`2.?6 (CCPA 197.’). Even if this doctrine were relevant and even if there were limits to it, these
`
`would not apply here, either for the previous claims or the current claims. The public is clearly
`
`informed of the limits oflhe claimed subject matter In both cases and of how to carry out the
`
`invention as claimed. Moreover, it is not clear to what multiple medication levels the Examiner
`
`refers. As is true for any open formulation claims, rnedicamcnts other than those specifically
`
`recued are included_ However, the statute merely requires that the in vcntion as recited in the
`
`claims be disclosed, not every possible variation which might be included. The Examiner also
`
`raises the issue of unexpected results. Apglicants have not previously or now chosen to rely on
`
`any unexpected results.
`
`The Commissioner is hereby authorized to charge any fees associated with this response
`
`or credit any overpayment to Deposit Account No. 13-3402.
`
`Respectfully submitted,
`
`
`
`eaney, Reg. No. 32,542
`Anthony J. Zelano, Reg. No. 27,969
`Attorncyffirgent for AppIicant(s)
`
`MILLEN, WPIITE, ZELANO
`«'1: BRANIGAN, PL‘.
`
`Arlington Courthouse Plaza 1, Suite 1400
`2200 Clarendon Boulevard
`
`Arlington, Virginia 22201
`Telephone: (703) 243-6333
`Facsimile: (703) 243-6410
`Attorney Docket No.; Pl-iAR.M.A-142 PI
`
`Date: April 21, 2003
`K'\Pnan1-n\l42\pl map;
`
`6
`
`PHARMA4 42 P 1
`
`Amerigen Ex. 1067, p. 6
`Amerigen Ex. 1067, p. 6