Docket No.: 085199-0034
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`PATENT
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of
`
`:
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`Customer Number: 20277
`
`Amir SHOJAEI
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`Application No.:
`1 1:’383,066
`Filed: May 12, 2006
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`Confirmation Number: 7083
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`Group Art Unit: 1618
`Examiner: Micah Paul YOUNG
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`For:
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`CONTROLLED DOSE DRUG DELIMERY SYSTEM
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`AMENDMENT
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`Mail Stop Amendment
`Commissioner for Patents
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`PO. Box 1450
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`Alexandria, VA 22313-1450
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`Sir:
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`This is in response to the non-final Office Action mailed October 7, 2013. A petition for
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`a one-month extension of time accompanies this response.
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`Amendments to the claims are reflected in the listing of the claims begi.nning on page 2
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`of this paper.
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`Remarksfarguments begin on page 7 of this paper.
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`To the extent necessary, a petition for an extension of time under 3? 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 500417 and please credit any excess fees to
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`such deposit account.
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`Amerigen Ex. 1014, p. 1
`Amerigen Ex. 1014, p.
`1
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`

`
`Application No.:
`
`llf383,066
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`Listing of the Claims
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`1.
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`(Previously presented) A pharmaceutical composition comprising:
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`(a)
`
`an
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`immediate release bead comprising at least one amphetamine salt; (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 incorporated 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.
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`(Canceled)
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`2
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`Amerigen Ex. 1014, p. 2
`Amerigen Ex. 1014, p. 2
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`

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`Application No.: 11,383,066
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`7.
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`(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
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`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.]a51) afier
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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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`1053 nghrfml.
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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 (AUCg-;r.r) after administration of
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`a 37.5 mg dose of the pharmaceutical composition to a human patient is about 1085 nghr/ml.
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`10.
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`(Original) The pharmaceutical composition of claim 1, wherein the d-
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`amphetamine Tm,‘
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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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`11.
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`(Original) The pharmaceutical composition of claim 1, wherein the
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`l-
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`amphetamine Cm, 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
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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 the last measured time (AUCo-1,,_.,t) 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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`3
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`Amerigen Ex. 1014, p. 3
`Amerigen Ex. 1014, p. 3
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`

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`Application No.: 1ll383,l]66
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`13.
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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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`amphetamine area under the curve from time 0 to time infinity (AUCo.inf) after administration of
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`a 37.5 mg dose of the pharmaceutical composition to a human patient is about 373 nghrfml.
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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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`1-
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`amphetamine 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 head 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
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`selected from the group consisting of dextroamphetamine sulfate,
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`4
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`Amerigen Ex. 1014, p. 4
`Amerigen Ex. 1014, p. 4
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`

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`Application No.:
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`lll383,066
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`dextroamphetamine saccharate, amphetamine aspartate monohydrate, amphetamine sulfate, 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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`(Previousiy presented) The composition of claim 1, 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 13.75 mg.
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`26.
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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 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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`5
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`Amerigen Ex. 1014, p. 5
`Amerigen Ex. 1014, p. 5
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`

`
`Application No.:
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`l1»’383,066
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`30.
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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 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 amphetamine 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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`(Previously presented) The pharmaceutical composition of claim 1, wherein a
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`protective coating is layered between the delayed release coating and the sustained release
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`coating.
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`6
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`Amerigen Ex. 1014, p. 6
`Amerigen Ex. 1014, p. 6
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`

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`Application No.: 1113834166
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`Remarks
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`Claims 1-5, 7-32, and 62 are pending.
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`Rejections under 35 U.S.C. § l03(a1
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`1.
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`Claims 1-5, 17, 18 and 23 have been rejected under 35 U.S.C. § l03(a) as obvious
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`over U.S. Publication No. 2003/0157173 (Percel) in view of U.S. Publication No. 2003/0050620
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`(Odidi). According to the Examiner, Percel discloses: “a timed pulse release system comprising
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`an immediate release bead comprising an active agent, a delayed release bead comprising the
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`drug and a coating and a sustained release coating over the delayed release [sustained coating]."
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`Office Action, p. 3. Odidi discloses: “a controlled release fonnulation where various active
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`agents are differentially released including propranolol and amphetamine salts are delivered to a
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`patient.” Id. The Examiner states that it would have been obvious to substitute the amphetamine
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`of Odidi for the propranolol of Percel. Applicants respectiiully traverse this rejection.
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`The instant claims require a second delayed release bead that provides sustained release
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`and has a construction wherein a delayed release coating is layered onto the amphetamine core,
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`and a sustained release coating is layered onto the delayed release coating. Thus, fi'om inside-
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`out, the claimed second delayed release bead comprises an amphetamine core, a delayed release
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`coating, and a sustained release coating.
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`Such a coating structure is not disclosed or suggested in Percel. Rather, Percel teaches,
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`from inside-out, a core containing an active agent, a sustained release coating, and a “Timed
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`Sustained Release” coating. According to Percel, a Timed Sustained Release coating delays
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`release until after a lag time, i.e., it is a delayed release coating. Perccl states that:
`
`7
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`Amerigen Ex. 1014, p. 7
`Amerigen Ex. 1014, p. 7
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`

`
`Application No.: 1lf383,066
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`The invention also provides a method of making a timed, sustained release dosage
`form comprising the steps of:
`1.
`preparing an active—containing core by coating an inert particle... to
`form an immediate release (IR) bead;
`2.
`coating the core with a plasticized solution or suspension of a water
`insoluble polymer to form sustained release (SR) coated drug particle;
`3.
`coating the SR coated particle with a mixture of plasticized water
`insoluble and enteric polymers to form a Timed Sustained Release.(TSR) coated
`drug particle ...
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`Percel, para. 13-16.
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`The active Containing cores . .. may be coated with one or two layers of polymers
`.... The inner layer membrane, which largely controls the rate of release following
`imbibition of water or body fluids into the core
`The outer membrane, which
`largely controls the lag time [i.e., delayed release] of up to 6 hours
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`Percel, para. 25-26.
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`The present invention addresses the need for a long-acting amphetamine composition that
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`meets the need of ADHD patients with longer-day demands.1 In a typical construction, a bead
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`includes a sustained release coating covered by a delayed release coating. See, Specification,
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`para. 23. This is the typical construction disclosed in Percel. Such a construction is not suitable,
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`however, for the instant invention because it results in a Tmax that is too early to meet the longer-
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`day requirements.
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`Id. The claimed second delayed release bead (the head that meets the longer-
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`day needs) has a construction that is atypical, and just the opposite of what is taught in Percel.
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`That is, the claimed second delayed release bead comprises a delayed release coating that is
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`covered by a sustained release coating. Id. at, e.g., para. 26.
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`Odidi does not provide the missing teaching. Odidi teaches a controlled release delivery
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`device including a vehicle (including an active agent, an amino acid, a buffer and a polymer),
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`which is provided within a housing. See, Odidi, e.g., paras. 14-15. Odidi teaches that one or
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`' As used herein, patients with “longer-day demands,” “longer-day needs," or “longer-day requirements” are ADHD
`patients who require a clinical benefit beyond 10-12 hours. See, Specification, para. 19.
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`3
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`Amerigen Ex. 1014, p. 8
`Amerigen Ex. 1014, p. 8
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`

`
`Application No.: 11;‘383,066
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`more of the vehicles may be coated with a polymeric coating. Id. at 17. According to Odidi,
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`controlled release delivery may be achieved by conventional
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`technologies,
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`such as a
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`homogenous blend of polymer, active substance, and excipients. Id. at 35. Odidi does not teach
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`or suggest a delayed release bead comprising at least one amphetamine salt 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-
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`For the reasons stated above, no combination of the references discloses or suggests the
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`claimed composition. Accordingly, applicants request that this rejection be withdrawn.
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`2.
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`Claims 1, 7-32, and 62 have been rejected as obvious over Percel, Odidi, and U.S.
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`Patent No. 6,605,300 (Burnside). The Examiner acknowledges that Percel and Odidi do not
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`teach the specific range of amphetamine present in the controlled release formulation. The
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`Examiner states that Burnside teaches an oral pulsed release formulation comprising a
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`combination of immediate release and delayed release amphetamine beads.
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`Applicants respectfully traverse this rejection. As stated in (1), above, no combination of
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`Percel and Odidi discloses or suggests that claimed construction of the second delayed release
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`bead. Burnside teaches immediate release and delayed pulsed release amphetamine beads.
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`Burnside does not teach an amphetamine salt layered onto or incorporated into a core; a delayed
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`release coating layered onto the amphetamine core; and a sustained release coating layered onto
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`the delayed release coating. Thus, no combination of the references teaches a bead that meets
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`the longer-day needs of certain ADHD patients.
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`9
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`Amerigen Ex. 1014, p. 9
`Amerigen Ex. 1014, p. 9
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`

`
`Application No.:
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`ll!'383,066
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`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 Examiner’s amendment or a supplemental amendment, the Examiner is
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`respectfully requested to contact the undersigned.
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`Respectfully submitted,
`
`MCDERMOTT WILL & EMERY LLP
`
`./Paul M. Zagan’
`
`Paul M. Zagar
`Registration No. 52,3 92
`
`Please recognize our Customer No. 20277
`as our correspondence address.
`
`340 Madison Avenue
`New York, NY 10173
`Phone: 212.547.5400 PMZ:tt
`
`Facsimile: 202.756.8087
`
`Date: January 24, 2014
`
`10
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`Amerigen Ex. 1014, p. 10
`Amerigen Ex. 1014, p. 10