PTO SB:'3O
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`Refiuest
`or
`Continued Examination (RCE)
`Transmittal
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`Address to:
`Mail Stop RCE
`Com mlssloner for Parents
`P.O. E011-I$5'|J
`Alexandria. vi: 2231 3.1450
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`A Iication Number
`F""‘ “'19
`First Named Inventor
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`Art Unit
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`111383.066
`Ma
`'2» 2°05
`Arnir Sho'aei
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`Examiner Name
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`Attome Docket Number
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`Micah Pam Y°“"' '
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`085199-0034
`This is a Request for Continued Examination {ROE} under 37 CFR 1.114 of the above-identified application.
`Request for Continued Examination (ROE) practice under 37 CFR 1.114 does not apply to any utility or plant application filed prlorto June
`8, 1995. or to a ny design eppl icalion.
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`1- 3|-|bmi35i°|'| Tefiuired Under 37 CFR 1-1 14 Note: If the RCE is proper, any previously filed unentered amen dmenls and
`amendments enclosed with the ROE will be entered in the order in which they were filed unless appiicant instructs otherwise.
`If
`applicant does not wish to he ve any previously tiled unentered arnendmentisl entered, applicant must req uest non-entry oi such
`amendrnentis).
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`a_
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`If a final Oflice action is outstanding. any amendments filed afier the final Offioe action
`Previously submitted.
`may be considered as a submission even if this box is not checked.
`i. Cl Consider the arguments in the Appeal Brief or Reply Brief previously tiled on
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`ii. Bother
`l:-.E| Enclosed
`i.
`IE AmendrnentlReply
`ii.
`i:|Aflidavit(s)r‘Dec|aration(s)
`2. Miscellaneous
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`iii. El information Disclosure Statement (IDS)
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`iv.
`|:]0ther
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`a. D Suspension of action on the above-identified application is requested under 3? CFR 1.103(c) for a
`period of
`months. (Period of suspension shall not exceed 3 months; Fee under 37 CFR 1_17(i} required)
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`b. E‘ Other
`The act: tee under 37 CFR 1.17(e) is required by 37 CFR 1.114 when the RCE is filed.
`The Director is hereby authorized to charge the following fees. any underpayment of fees. or credit any
`overpayments to Deposit Account No.
`50-0417
`.
`I have enclosed a duplicate copy of this sheet.
`i. El RCE fee required under 3'.-' CFR 1.17{e)
`ii. El Extension of time fee (37 CFR1.136 and1.1‘i']
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`iii. El Other
`b. [:| Check in the amount of S
`c. a Payment by credit card (Form PTO-2038 enclosed)
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`ICA T, ATTORNEY, OR AGENT REQUIRED
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`3.
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`a.
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`enclosed
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`M.
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`NYK13?‘i"283-1.D55199.0Cl34
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`Amerigen Ex. 1012, p. 1
`Amerigen Ex. 1012, p.
`1
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`

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`Docket N0.: 08.5199-0034
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`PATENT
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of
`Amir SHOJAEI
`1 l{3'83,066
`Application No.:
`Filed: May 12, 2006
`
`:
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`Customer Number: 20277
`Confirmation Number: 7083
`Group Art Unit: 1618
`Examiner: Micah Paul YOUNG
`
`For:
`
`CONTROLLED DOSE DRUG DELITIERY SYSTEM
`
`AMENDMENT
`
`Mail Stop AF
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`This is in response to the final Office Action mailed October 12, 2010. A Request for
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`Continued Examination (RCE) and the required fee accompany this response.
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`Amendments to the claims are reflected in the listing of the claims beginning on page 2
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`of this paper.
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`Renlarksiarguments begin on page 7 of this paper.
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`To the extent necessary, a petition for an extension of time under 37 C.F.R. 1.136 is
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`hereby made. Please charge any shortage in fees due in connection with the filing of this paper,
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`including extension of time fees, to Deposit Account 5004]’? and please credit any excess fees to
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`such deposit account.
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`Amerigen Ex. 1012, p. 2
`Amerigen Ex. 1012, p. 2
`
`

`
`Application No.:
`
`llJ'383,I}66
`
`Listing of the Claims
`
`1.
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`(Currently amended) A pharmaceutical composition comprising: (a) an immediate
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`release bead comprising at
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`least one amphetamine salt;
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`(b) a first delayed release bead
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`-comprising at least one amphetamine salt; and (c) a second delayed release bead comprising at
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`least one amphetamine salt; wherein the first delayed release bead provides pulsed release of the
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`at least one amphetamine salt and the second delayed release bead provides sustained release of
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`the at least one amphetamine salt;
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`wherein the second delayed release bead comprises at least one amphetamine salt layered
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`onto or inco1_'porated into a core; a delayed release coating layered onto the amphetamine core;
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`and a sustained release coating layered onto the delayed release coating.
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`2.
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`(Original) The pharmaceutical composition of claim 1, wherein the first delayed
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`release bead and the second delayed release bead comprise an enteric coating.
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`3.
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`(Original) The pharmaceutical composition of claim 2, wherein the enteric
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`coating is pH dependent.
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`4.
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`(Original) The pharmaceutical composition of claim 2, wherein the first delayed
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`release bead and the second delayed release bead comprise different enteric coatings.
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`5.
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`(Original) The pharmaceutical composition of claim 2, wherein the first delayed
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`release bead and the second delayed release bead comprise the same enteric coating.
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`6.
`
`(Canceled)
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`Amerigen Ex. 1012, p. 3
`Amerigen Ex. 1012, p. 3
`
`

`
`Application No.: 11/383,066
`
`7.
`
`(Original) The pharmaceutical composition of claim 1, wherein administration of
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`a 37.5 mg dose of the pharmaceutical composition to a human patient results in a d-amphetamine
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`Cm,‘ of about 50 ng/ml.
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`8.
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`(Original) The pharmaceutical composition of claim 1, wherein the d-
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`amphetamine area under the curve from time 0 to the last measured time (AUCo.1a31) after
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`administration of a 37.5 mg dose of the pharmaceutical composition to a human patient is about
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`1058 nghr/'ml.
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`9.
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`(Original) The pharmaceutical composition of claim 1, wherein the d-
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`amphetamine area under the curve from time 0 to time infinity (AUCO-jnf) after administration of
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`a 37.5 mg dose of the pharmaceutical composition to a human patient is about 1085 nghrfml.
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`10.
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`(Original) The pharmaceutical composition of claim 1, wherein the d-
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`amphetamine Tmax
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`is about 8.2 hours after administration of a 37.5 mg dose of the
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`pharmaceutical composition to a human patient.
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`1 1.
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`(Original) The pharmaceutical
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`composition of claim 1, wherein the
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`[-
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`amphetamine Cmx after administration of a 37.5 mg dose of the pharmaceutical composition to a
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`human patient is about 15 ng/ml.
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`12.
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`(Original) The pharmaceutical composition of claim 1, wherein the
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`1-
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`amphetamine area under the curve from time 0 to the last measured time (AUC()_]as[) after
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`administration of a 37.5 mg dose of the pharmaceutical composition to a human patient is about
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`354 nghrfml.
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`Amerigen Ex. 1012, p. 4
`Amerigen Ex. 1012, p. 4
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`

`
`Application No.:
`
`ll!'383,066
`
`13.
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`(Original) The pharmaceutical
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`composition of claim 1, wherein the
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`1-
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`amphetamine area under the curve from time 0 to time infinity (AUCg.;,,f) after administration of
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`a 37.5 mg dose of the pharmaceutical composition to a human patient is about 373 nghr/ml.
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`14.
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`(Original) The pharmaceutical
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`composition of claim 1, wherein the
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`l-
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`amphetarnine Tm.
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`is about 8.4 hours after administration of a 37.5 mg dose of the
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`pharmaceutical composition to a human patient.
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`15.
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`(Original) The pharmaceutical composition of claim 1, wherein the immediate
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`release bead and at least one delayed release bead are present on a single core.
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`16.
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`(Original) The pharmaceutical composition of claim 1, wherein the immediate
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`release bead and at least one delayed release bead are present on different cores.
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`1?.
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`(Original) The pharmaceutical composition of claim 1, wherein the at least one
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`amphetamine salt is coated onto a core.
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`18.
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`(Original) The pharmaceutical composition of claim 1, wherein the at least one
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`amphetamine salt is incorporated into a core.
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`19.
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`(Original) The pharmaceutical composition of claim 2, which further comprises a
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`protective layer over at least one enteric coating.
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`20.
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`(Original) The pharmaceutical composition of claim 2, which further comprises a
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`protective layer between the amphetamine salt and at least one enteric coating.
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`21.
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`(Original) The pharmaceutical composition of claim 1, wherein the at least one
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`amphetamine salt
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`is selected from the group consisting of dextroamphetamine sulfate,
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`Amerigen Ex. 1012, p. 5
`Amerigen Ex. 1012, p. 5
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`

`
`Application No.:
`
`l12‘383,066
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`dextroamphetamine saccharate, amphetamine aspartate monohydrate, amphetamine suifate, and
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`mixtures thereof.
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`22.
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`(Original) The pharmaceutical composition of claim 21, wherein the at least one
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`amphetamine salt is a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate,
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`amphetamine aspartate monohydrate, and amphetamine sulfate.
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`23.
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`(Original) The pharmaceutical composition of claim 1, wherein the composition
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`does not exhibit a food effect.
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`24.
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`(Previously presented) The composition of claim I, wherein the amount of at least
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`one amphetamine salt is about 12.5 mg.
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`25.
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`(Previously presented) The composition of claim 1, wherein the amount of at least
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`one amphetamine salt is about 18.75 mg.
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`26.
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`(Previously presented) The composition of claim I, wherein the amount of at least
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`one amphetamine salt is about 25 mg.
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`27.
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`(Previously presented) The composition of claim 1, wherein the amount of at least
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`one amphetamine salt is about 31.25 mg.
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`28.
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`(Previously presented) The composition of claim 1, wherein the amount of at least
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`one amphetamine salt is about 37.5 mg.
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`29.
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`(Previously presented) The composition of claim 1, wherein the amount of at least
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`one amphetamine salt is about 43.75 mg.
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`Amerigen Ex. 1012, p. 6
`Amerigen Ex. 1012, p. 6
`
`

`
`Application No.: 11:‘383,066
`
`30.
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`(Previously presented) The composition of claim I, wherein the amount of at least
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`one amphetamine salt is about 50 mg.
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`31.
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`(Previously presented) The composition of claim 1, wherein the amount of at least
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`one amphetarnine salt is about 62.5 mg.
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`32.
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`(Previously presented) The composition of claim 1, wherein the amount of at least
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`one amphetamine salt is about 75 mg.
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`33-61 . (Canceled)
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`62.
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`(New) The pharmaceutical composition of claim 1, wherein a protective coating
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`is layered between the delayed release coating and the sustained release coating.
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`Amerigen Ex. 1012, p. 7
`Amerigen Ex. 1012, p. 7
`
`

`
`Application No.: 11/383,066
`
`Remarks
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`Claims 1-5, 7-32, and 62 are pending. Claim 1 has been amended to recite that the
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`second delayed release bead comprises at
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`least one amphetamine salt
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`layered onto or
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`incorporated into a core; a delayed release coating layered onto the amphetamine core; and a
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`sustained release coating layered onto the delayed release coating. Support for the claim 1
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`amendment and new claim 62 can be found in the specification at paragraphs 23-24.
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`Reection under 35 U.S.C.
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`102
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`Claims 1-5, 'i'—23, 25, and 26 have been rejected under 35 U.S.C. § l02(b) as anticipated
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`by U.S. Patent No. 6,605,300. According to the Examiner, the ‘300 patent teaches “an oral
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`pulsed release formulation comprising a combination of immediate release and delayed release
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`amphetamine beads.” Office Action, p. 2 (emphasis added).
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`The Examiner states that the ‘300 patent anticipates the instant claims because the beads
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`according to the ‘300 patent, and the instantly claimed first and second delayed pulsed release
`beads can include the same enteric polymer. Office Action, p. 6. According to the Examiner,
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`claiming pulsed release and sustained release amounts to reciting intended uses, and not
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`structural differences. Id.
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`Applicants respectfully traverse this rejection. The Examiner does not take into account
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`that materials may be used or structured in different ways to achieve different results. One of
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`ordinary skill
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`in the art would have looked to the specification for guidance and, from the
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`specification, ascertained that the second delayed release head has an atypical construction, i.e.,
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`an atypical layering of the materials. Such a construction is neither disclosed nor suggested in
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`the prior art. Typically, a delayed, sustained release bead is constructed with a delayed release
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`Amerigen Ex. 1012, p. 8
`Amerigen Ex. 1012, p. 8
`
`

`
`Application No.:
`
`ll;’383,066
`
`coating overlaying a sustained release coating. Specification, paragraph 23.
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`This typical
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`construction results in a Tmax occurring too early, with the consequence that a patient’s longer-
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`day requirements for ADHD treatment are not met. Id.
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`In order to expedite prosecution, claim 1 has been amended to recite that the second
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`delayed release bead comprises at least one amphetamine salt layered onto or incorporated into a
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`core; a delayed release coating layered onto the amphetamine core; and a sustained release
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`coating layered onto the delayed release coating. This construction is counterintuitive and
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`unexpectedly provides drug release that
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`to meet a patient’s longer day ADHD treatment
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`requirements, when administered with an immediate release bead and a first delayed release bead
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`according to the present invention.
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`The ‘300 patent teaches delayed release beads having a drug—containing core coated with
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`an enteric polymer (Examples 2 and 3), and delayed release beads having a drugvcontaining core
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`coated with an enteric polymer which, in turn, is coated with SURELEASE. Thus, 300 patent
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`Examples 2 and 3 disclose a bead with one coating, and do not disclose a bead comprising a
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`delayed release coating and a sustained release coating. Example 4 of the ‘300 patent discloses a
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`head with layers in a “typical” construction.
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`Thus,
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`the ‘30O patent does not disclose a
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`pharmaceutical composition comprised of the instantly claimed three beads. Accordingly, this
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`rejection should be withdrawn.
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`Re'ection under 35 U.S.C.
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`103 a
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`Claims 1-5 and 7-32 have been rejected under 35 U.S.C. § 103(a) as obvious over the
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`‘300 patent. According to the Examiner, the ‘300 patent discloses beads comprising a mixture of
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`amphetamine salts having a concentration of at least 20 mgs. The Examiner acknowledges that
`
`Amerigen Ex. 1012, p. 9
`Amerigen Ex. 1012, p. 9
`
`

`
`Application No.: 11/383,066
`
`the instant claims “differ from the reference by reciting various concentrations of the active
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`ingredient(s).” Office Action, p. 5. The Examiner states that the preparation of pharmaceutical
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`compositions having various amounts of the active ingredient is “within the level of skill of one
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`having ordinary skill in the art.” Id.
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`As stated above, the instant claims require a second delayed release bead that provides
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`sustained release and having a construction wherein a delayed release ‘coating is layered onto the
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`amphetamine core; and a sustained release coating is layered onto the delayed release coating.
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`The ‘300 patent neither discloses nor suggests such a construction. The instantly claimed second
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`delayed release bead postpones release of the drug after administration and then releases the drug
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`for an extended period of time.
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`Intuitively, such a head would be expected to have a delayed
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`release coating external
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`to the sustained release coating because the delayed release occurs
`
`before the sustained release. Such a construction, however, does not provide a release to meet
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`the longer day needs for ADHD treatment because the Trnax occurs too soon. Surprisingly the
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`instantly claimed, counterintuitive construction does work.
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`Thus,
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`this rejection should be
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`withdrawn.
`
`Amerigen Ex. 1012, p. 10
`Amerigen Ex. 1012, p. 10
`
`

`
`Application No.: 11:’383,066
`
`Conclusion
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`This application is believed to be in condition for allowance. If any issues remain which
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`may be addressed by an Exan1iner’s amendment or a supplemental amendment, the Examiner is
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`respectfully requested to contact the undersigned.
`
`Respectfully submitted,
`
`M7RMOTI'
`
`LL & EMERY LLP
`
`Paul M. Zagar
`Registration No. 52,392
`
`Please recognize our Customer No. 20277
`as our correspondence address.
`
`600 13th Street, N.W.
`Washington, DC 20005-3096
`Phone: 212.547.5400 PMZ:MWE
`
`Facsimile: 202.756.8087
`
`Date: January 12, 2011
`
`10
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`Amerigen Ex. 1012, p. 11
`Amerigen Ex. 1012, p. 11