Docket No.: 085199-0034
`
`PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of
`AmirSHO.lAEI
`
`llJ'383,066
`Application No.:
`Filed: May 12, 2006
`
`: Customer Number: 20277
`Confirmation Number: 7083
`
`Group Art Unit: 1618
`Examiner: Micah Paul YOUNG
`
`For:
`
`CONTROLLED DOSE DRUG DELI\'!'ERY SYSTEM
`
`AMENDMENT
`
`Mail Stop AF
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`Madam:
`
`This is in response to the final Office Action mailed April 30, 2014. A request for
`
`consideration under AFCP 2.0 accompanies this response.
`
`Amendments to the claims a1'e reflected in the listing of the claims beginning on page 2
`
`of this paper.
`
`Remarksfarguments begin on page 7 of this paper.
`
`To the extent necessaiy, a petition for an extension of time under 37 CFR. 1.136 is
`
`hereby made. Please cha1'ge any shortage in fees due in connection with the tiling of this paper,
`
`including extension of time fees, to Deposit Account 500417 and please credit any excess fees to
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`such deposit account.
`
`Amerigen Ex. 1016, p. 1
`Amerigen Ex. 1016, p.
`1
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`

`
`Application No.: 11,883,066
`
`Listing of the Claims
`
`1.
`
`(Currently amended) A pharmaceutical composition comprising: (a) an immediate
`
`release bead comprising at
`
`least one amphetamine salt;
`
`(b) a first delayed release bead
`
`comprising at least one amphetamine salt; and (c) a second delayed release bead comprising at
`
`least one amphetamine salt; wherein the first delayed release bead provides pulsed release of the
`
`at least one amphetamine salt and the second delayed release bead provides sustained release of
`
`the at least one amphetamine salt;
`
`wherein the second delayed release bead comprises at least one amphetamine salt layered
`
`onto or incorporated into a co1'e; a delayed release coating laye1'ed onto the amphetamine co1'e;
`
`and a sustained release coating layered onto the delayed release coating; and
`
`wherein the first delayed release bead and the second delayed release bead comprise an
`
`enteric coating.
`
`2.
`
`3.
`
`(Canceled)
`
`(Currently amended) The pharmaceutical composition of claim [2] l, wherein the
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`enteric coating is pH dependent.
`
`4.
`
`(Currently amended) The pharmaceutical composition of claim [2] 1, wherein the
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`first delayed release bead and the second delayed release bead comprise different enteric
`
`coatings.
`
`5.
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`(Currently amended) The pharmaceutical composition of claim [2] l, wherein the
`
`first delayed release bead and the second delayed release bead comprise the same enteric coating.
`
`6.
`
`(Canceled)
`
`Amerigen Ex. 1016, p. 2
`Amerigen Ex. 1016, p. 2
`
`

`
`Application No.: 11,883,066
`
`7.
`
`(Original) The pharmaceutical composition of claim 1, wherein administration of
`
`a 37.5 mg dose of the pharmaceutical composition to a human patient results in a d—amphetarnine
`
`Cum of about 50 ng/ml.
`
`8.
`
`(Original) The pharmaceutical
`
`composition of claim I, wherein the d-
`
`amphetamine area under the curve from time 0 to the last measured time (AUCg_1.m) after
`
`administration of a 37.5 mg dose of the pharmaceutical composition to a human patient is about
`
`1058 nghrfml.
`
`9.
`
`(Original) The pharmaceutical
`
`composition of claim I, wherein the d-
`
`amphetamine area under the curve from time 0 to time infinity (AUC[H,.;) after administration of
`
`a 37.5 mg dose of the pharmaceutical composition to a human patient is about 1085 nghr/ml.
`
`10.
`
`(Original) The phaimaceutical
`
`composition of claim 1, wherein the d-
`
`amphetamine Tam is about 8.2 hours after administration of a 37.5 mg dose of
`
`the
`
`pharmaceutical composition to a human patient.
`
`11.
`
`(Original) The pharmaceutical
`
`composition of claim 1, wherein the
`
`l-
`
`amphetamine Cm“ after administration of a 37.5 mg dose of the pharmaceutical composition to a
`
`human patient is about 15 ng/ml.
`
`12.
`
`(Original) The pharmaceutical composition of claim 1, wherein the
`
`1-
`
`amphetamine area under the curve from time 0 to the last measured time (AUC(}_[a5t) after
`
`administration of a 37.5 mg dose of the pharmaceutical composition to a human patient is about
`
`354 nghrfml.
`
`Amerigen Ex. 1016, p. 3
`Amerigen Ex. 1016, p. 3
`
`

`
`Application No.: 11,883,066
`
`13.
`
`(Original) The pharmaceutical composition of claim 1, wherein the
`
`1-
`
`amphetamine area under the curve from time 0 to time infinity (AUCu_;,,f) after administration of
`
`a 37.5 mg dose of the phannaceutical composition to a human patient is about 373 nghrfml.
`
`14.
`
`(Original) The pharmaceutical composition of claim 1, wherein the
`
`l-
`
`amphetamine Tm“ is about 8.4 hours after administration of a 37.5 mg dose of
`
`the
`
`pharmaceutical composition to a human patient.
`
`15.
`
`(Original) The pharmaceutical composition of claim 1, wherein the immediate
`
`release bead and at least one delayed release bead are present on a single core.
`
`16.
`
`(Original) The pharmaceutical composition of claim 1, wherein the immediate
`
`release bead and at least one delayed release head are present on different cores.
`
`1?.
`
`(Original) The pharmaceutical composition of claim 1, wherein the at least one
`
`amphetamine salt is coated onto a co1'e.
`
`18.
`
`(Original) The pharmaceutical composition of claim 1, wherein the at least one
`
`amphetamine salt is incorporated into a core.
`
`19.
`
`(Currently amended) The pharmaceutical composition of claim [2] L, which
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`further comprises a protective layer over at least one enteric coating.
`
`20.
`
`(Currently amended) The pharmaceutical composition of claim [2] l, which
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`further comprises a protective layer between the amphetamine salt and at least one enteric
`
`coating.
`
`Amerigen Ex. 1016, p. 4
`Amerigen Ex. 1016, p. 4
`
`

`
`Application No.: 11,883,066
`
`21.
`
`(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,
`
`dextroamphetamine saccharate, amphetamine aspartate monohydrate. amphetamine sulfate, and
`
`mixtures thereof.
`
`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.
`
`23.
`
`(Original) The pharmaceutical composition of claim 1, wherein the composition
`
`does not exhibit a food effect.
`
`24.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 12.5 mg.
`
`25.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 18.25 mg.
`
`26.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 25 mg.
`
`27.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 31.25 mg.
`
`28.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 37.5 mg.
`
`Amerigen Ex. 1016, p. 5
`Amerigen Ex. 1016, p. 5
`
`

`
`Application No.: 11,883,066
`
`29.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 43.75 mg.
`
`30.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 50 mg.
`
`31.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 62.5 mg.
`
`32.
`
`(Previously presented) The composition of claim 1, wherein the amount of at least
`
`one amphetamine salt is about 75 mg.
`
`33-61. (Canceled)
`
`62.
`
`(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
`
`coating.
`
`Amerigen Ex. 1016, p. 6
`Amerigen Ex. 1016, p. 6
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`

`
`Application No.: 11,883,066
`
`Remarks
`
`Claims 1, 3-5, 7-32, and 62 are pending. Claim 1 has been amended to incorporate the
`
`subject matter of claim 2. Claim 2 has been canceled. Claims 3-5, 19, and 20 have been
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`amended to depend upon claim 1.
`
`Rejections under 35 U.S.C. § 103131
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`1.
`
`Claims 1-5, 17, 18 and 23 have been rejected unde1' 35 U.S.C. § l03(a) as obvious
`
`over US. Publication No. 2003i'0l57l73 (Percel) in view of US. Publication No. 2003fU05062U
`
`(Odidi). According to the Examiner, Percel discloses: “a timed pulse release system comprising
`
`an immediate release bead comprising an active agent, a delayed release bead comprising the
`
`drug and a coating and a sustained release coating ove1' the delayed release [sustained coating].”
`
`Office Action, p. 2-3.
`
`The Examiner states that Odidi discloses: “a controlled release
`
`formulation where various active agents a1'e differentially released including p1'opranolol and
`
`amphetamine salts are delivered to a patient.” Id. at 3. The Examiner states that it would have
`
`been obvious to substitute the amphetamine of Odidi fo1' the propranolol of Pe1'cel.
`
`Applicants respectfully traverse this rejection. The instant claims are directed to an
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`amphetamine salt pharmaceutical composition including three beads: an immediate release bead,
`
`a first delayed release bead that provides pulsed release, and a second delayed release bead that
`
`provides sustained release. The instant claims further require that the second delayed release
`
`bead has a construction wherein a delayed release coating is layered onto the amphetamine core,
`
`and a sustained release coating is layered onto the delayed release coating. Thus, from inside-
`
`out, the claimed second delayed release bead comprises an amphetamine core, a delayed release
`
`coating, and a sustained release coating.
`
`Amerigen Ex. 1016, p. 7
`Amerigen Ex. 1016, p. 7
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`

`
`Application No.: 11,883,066
`
`No combination of Percel and Odidi discloses 01' suggests: (1) a three bead, amphetamine
`
`salt pharmaceutical composition including an immediate release bead, a delayed release bead
`
`that provides pulsed release, and a delayed release bead that provides sustained release; and (2) a
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`second delayed release bead constructed according to the instant claims.
`
`The Examiner states that:
`
`Applicant is merely arguing the semantics of the coating layers, since the actual
`compounds applied to the core bead are identical to those of the instant claims.
`According to the instant Example 1,
`the “delayed release coating laye1'” is
`
`SURELEASE, an ethyl cellulose compound. The “sustained release coating
`layer” is a EUDRAGIT brand polymer. Percel discloses a coated bead with an
`inner coating of ethyl cellulose and an outer coating of a pH—sensitive methacrylic
`acid-methamethacrylate
`copolyme1's
`(EUDRAGIT polymers)
`[0026-0027].
`
`Although Percel designated these polymers differently than the instant claims,
`these polymers are identical to the instantly recited Example 1, and are disposed
`in an identical fashion in the instant claims.
`
`Office Action, p. 7.
`
`No combination of Percel and Odidi discloses or suggests the claimed th1'ee-bead
`A.
`composition comprising an immediate release bead, a first delayed release bead, and a second
`delayed release bead
`
`Applicants request that this rejection be withdrawn because no combination of Pe1'cel and
`
`Odidi discloses or suggests the instantly claimed phannaceutical composition comprising an
`
`immediate release bead, a first delayed release bead, and a second delayed release bead.
`
`Citing paragraphs l4—l6 of Percel, the Examiner states that Percel discloses a timed
`
`release system comp1'ising an immediate release bead, a delayed release bead, and a sustained
`
`release bead. Office Action, p. 2-3. Applicants respectfully disagree. Paragraphs 14-16 of Percel
`
`disclose a method of making a timed, sustained release dosage form. Percel teaches that an
`
`immediate release bead may be included in a capsule containing the sustained release bead. See,
`
`Percel, para. 6, 21, 33. There is no teaching in Pe1'cel of a pharmaceutical composition that
`
`includes three beads. More particularly, Percel does not disclose or suggest a composition that
`
`Amerigen Ex. 1016, p. 8
`Amerigen Ex. 1016, p. 8
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`

`
`Application No.: 11,883,066
`
`includes an immediate release bead, a first delayed release bead that provides pulsed release, and
`
`a second delayed release bead that provides sustained release.
`
`Odidi teaches a “controlled release delivery device that comprises a variety of different
`
`vehicles for delivering a variety of different pharmaceutical active agents concurrently in one
`
`simple oral dose.” Odidi, para. 4. Oididi
`
`teaches that different controlled release vehicles
`
`containing different active agents may be included in one housing for oral delivery. There is no
`
`teaching in Odidi that its housing may include an immediate release vehicle. As with Percel,
`
`Odidi does not teach a pharmaceutical composition including three beads and, more particularly,
`
`the instantly claimed immediate release bead, first delayed release bead, and second delayed
`
`release bead. Thus, for the reasons stated above, applicants request
`
`that
`
`this rejection be
`
`withdrawn.
`
`No combination of Percel and Odidi discloses or suggests a delayed release bead
`B.
`providing sustained release and comprising at
`least one amphetamine salt
`layered onto or
`incorporated into a core; a delayed release coating laye1'ed onto the amphetamine core; and a
`sustained release coating layered onto the delayed release coating
`
`According to the Examiner, Percel discloses a coated head with an inner coating of ethyl
`
`cellulose and an outer coating of pH-sensitive methacrylic acid-methamethac1'ylate copolymers
`
`(EUDRAGIT polymers). Office Action, p. 7. Thus, the Examiner states, the polymers are
`
`identical to the polymers in instant Example 1. Id.
`
`The Examiner further states that instant
`
`Example 1 discloses a delayed release coating and a sustained release coating. Office Action, p.
`
`T. Example 1 describes an immediate release formulation, which does not include such coatings.
`
`Applicants believe that the Examiner intended to cite Example 4, entitled “Sustained Release
`
`Formulation (HDR2).” Accordingly, applicants’ response addresses instant Example 4.
`
`Applicants respectfully disagree that Percel discloses or suggests the instantly claimed
`
`second delayed release bead.
`
`In fact, Percel teaches a typical bead construction, in which the
`
`Amerigen Ex. 1016, p. 9
`Amerigen Ex. 1016, p. 9
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`

`
`Application No.: 11,883,066
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`bead includes a sustained release coating covered by a delayed release coating. See,
`
`Specification, para. 23.
`
`('1)
`
`Percel does not reach a deferred release bead pr()vidz'rrg .s‘u.rrairred release rhar has
`
`an inner delayed release (_'0an'rrg
`
`The Examiner states that Percel discloses a coated head with an inner coating of ethyl
`
`cellulose, and that this coating is identical to the instantly claimed inner coating of the second
`
`delayed release bead. Office Action, p. 7. Applicants respectfully disagree.
`
`Percel does disclose that
`
`the inner coating is a wate1'
`
`insoluble polymer such as
`
`ethylcellulose.
`
`Percel, para. 25. The inner coating disclosed in the instant examples (i.e.,
`
`Example 4, not Example 1)
`
`is a MAAIMAIMMA copolymer (EUDRAGIT FS 30D).
`
`In
`
`Example 4, the intermediate formulation pellets from Example 2 weI'e sprayed by an additional
`
`coating. Thus, the inner coating of the Example 4 pellet (head) is the coating that was applied in
`
`Example 2, i.e., MAA/MA/MMA Copolymer Suspension (EUDRAGIT FS 30D). Specification,
`
`p. 28-29, Example 2 and p. 30, Example 4. Thus, the inner coating of Percel (ethylcellulose) is
`
`not
`
`identical
`
`to the inner coating of Example 4 (MAAIMAIMMA copolymer), and the
`
`differences between Percel and the instant claims a1'e not merely a matter of semantics.
`
`Accordingly, applicants request that this rejection be Withdrawn.
`
`(2)
`
`Percel’ does not reach an outer e()a3‘ir1g ideririeal to the in.s'ram‘l')= claimed .s'emnd
`
`delayed release bend miter i’.’()(H‘iJ‘1g
`
`According to the Examiner, Percel discloses a coated head with an outer coating of pH-
`
`sensitive methacrylic acid-methamethac1'ylate copolymers (EUDRAGIT polymers), and that this
`
`coating is identical to the instantly claimed outer coating of the second delayed release bead.
`
`The outer coating taught by Percel is a mixture of a wate1' insoluble polymer and an
`
`enteric polymer. Percel, paras. l l, 26, 33, Example 1, Example 3. Examples 1 and 3 of Percel
`
`disclose an outer coating that is a mixture of ethylcellulose (water insoluble polymer, Percel,
`
`10
`
`Amerigen Ex. 1016, p. 10
`Amerigen Ex. 1016, p. 10
`
`

`
`Application No.: 11,883,066
`
`para.33) and HPMCP (enteric polymer, Percel, para. 33). There is no teaching in Pe1'cel of an
`
`outer coating that is not a mixture of polymers. A sustained release, outer coating according to
`
`the instant claims may be, as exemplified in Example 4, ethylcellulose (SURELEASE). Thus,
`
`contrary to the Examiner, the outer coatings according to Percel and the instant examples are not
`
`identical. Further, one of ordinary skill in the art would not have expected the water insoluble
`
`polymer;"enteric polymer mixture of Percel to be functionally identical to the instantly claimed
`
`sustained release coating.
`
`(3)
`
`Odidi does not teach me r!aim.ed second delayed release bead
`
`Odidi does not teach a delayed release bead providing sustained release and comprising
`
`at least one amphetamine salt layered onto or incorporated into a core; a delayed release coating
`
`laye1'ed onto the amphetamine co1'e; and a sustained release coating layered onto the delayed
`
`release coating. Odidi teaches a housing for oral delivery that contains different controlled
`
`release vehicles containing different active agents. Thus, Odidi does not provide the teaching
`
`that is absent from Percel.
`
`In summary, no combination of Pe1'cel and Odidi discloses or suggests the claimed
`
`composition for the reasons stated in (A) and (B), above, each of which is an independent basis
`
`fo1' withdrawing the rejection.
`
`2.
`
`Claims 1, 7-32, and 62 have been rejected as obvious over Percel, Odidi, and U5.
`
`Patent No. 6,605,300 (Burnside). The Examiner acknowledges that Percel and Odidi do not
`
`teach the specific range of amphetamine present in the controlled release formulation. Burnside
`
`is relied upon by the Examiner to establish the level of skill in the art regarding specific ranges of
`
`amphetamine formulations. Office Action, p. 8.
`
`11
`
`Amerigen Ex. 1016, p. 11
`Amerigen Ex. 1016, p. 11
`
`

`
`Application No.: 11,883,066
`
`Applicants respectfully t1'ave1'se this rejection. As stated in (1), above, no combination of
`
`Percel and Odidi discloses or suggests a three bead amphetamine composition comprising an
`
`immediate release bead, a first delayed release bead that provides pulsed release, and a second
`
`delayed release bead that provides sustained release. Burnside teaches immediate release and
`
`delayed pulsed release amphetamine beads. Burnside does not teach a composition that further
`
`comprises a third bead, much less a third bead that provides sustained release after a lag time,
`
`i.e., a delayed release bead that provides sustained release. The addition of a third bead
`
`according to the instant claims results in a pharmaceutical composition that meets the longer—day
`
`needs of certain ADHD patients (about
`
`fou1' hours of additional coverage beyond that of
`
`ADDERALL XR). Burnside, Percel, and Odidi do not disclose or suggest such a composition.
`
`Thus, applicants respectfully request that this rejection be withdrawn.
`
`Conclusion
`
`This application is believed to be in condition for allowance.
`
`If any issues remain which
`
`may be addressed by an Examiner’s amendment or a supplemental amendment, the Examiner is
`
`respectfully requested to contact the undersigned.
`
`340 Madison Avenue
`New York, NY l01?'3
`Phone: 212.547.5400
`
`Facsimile: 202.756.8087
`
`Date: June 3,2014
`
`Respectfully submitted,
`
`MCDERMOTT WILL & EMERY LLP
`
`FPaul M. Zagarf
`
`Paul M. Zagar
`
`Registration No. 52,392
`
`Please recognize our Customer No. 20277
`as our correspondence address.
`
`12
`
`Amerigen Ex. 1016, p. 12
`Amerigen Ex. 1016, p. 12