Attorney Docket No. 21076-181
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Patent Application of:
`Curtis Wright et al.
`
`Application No.: 13/726,324
`
`Filed: December 24, 2012
`
`For:
`
`PHARMACEUTICAL FORMULATION
`CONTAINING GELLING AGENT
`
`Confirmation No.: TBA
`
`Art Unit: TBA
`
`Examiner: TBA
`
`Filed Electronically
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`Supplemental Amendment
`
`Prior to examination of the above-referenced application, Applicants submit the following:
`
`Amendments to the Claims begin on page 2 of this paper.
`
`Remarks begin on page 3 of this paper.
`
`21578/2
`Ol/23/2013 20371054.1
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`I.
`
`Amendments to the Claims
`
`1-70. Canceled.
`
`(New) An extended release abuse deterrent dosage form comprising:
`71.
`a. a core matrix comprising a blended mixture of:
`(a) PEO having a molecular weight of from about 300,000 to about 5,000,000;
`(b) magnesium stearate; and
`(c) oxycodone or a pharmaceutically acceptable salt thereof;
`wherein the matrix is heated to melt at least a portion of the PEO included in the matrix; and
`b. PEG applied onto the core matrix;
`wherein the dosage form provides extended release of the drug.
`
`-2-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`II.
`
`Remarks
`
`A. Status of the Claims
`Claims 1-70 are hereby canceled. New claim 71 is added.
`
`B. Remarks
`Pursuant to 37 C.F.R. § 41.202 and MPEP § 2304.02, Applicants declare that new claim 71
`as introduced herein is copied from US Patent No. 8,101,630 B2, which issued January 24, 2012
`to Kumar et al. ("Kumar") from U.S. Application No. 12/383,906.
`New claim 71 is identical to sole claim 1 of Kumar. Applicants urge that, as the instant
`claim 71 is copied from Kumar, the claims interfere; and further that the instant claim 71 (and
`Kumar claim 1) should constitute the count. As claim 71 is identical to issued claim 1 of Kumar,
`Applicants have identified a patentable claim as the count.
`As claim 1 is the only claim issued in Kumar, and as claim 71 is now the sole claim
`pending in the instant application, Applicants submit that the sole claim of the instant application
`interferes with the sole claim of Kumar, i.e., all claims pending in the instant application interfere
`with the sole issued claim ofthe patent.
`Applicants' support for new claim 71 (and claim 1 of Kumar, and the proposed count) is
`shown in the claim chart below.
`
`Claim 71
`[Claim 1 ofKumarl
`An extended release
`
`At page 6, lines 4-9:
`
`Supporting Disclosure
`USSN 10/214,412
`
`"The term "sustained release" is defined for purposes of the
`present invention as the release of the opioid analgesic from the
`oral dosage form at such a rate that blood (e.g., plasma)
`concentrations (levels) are maintained within the therapeutic
`range but below toxic levels over an extended period of time,
`e.g., from about 12 to about 24 hours as compared to an
`immediate release product. Preferably the sustained release is
`sufficient to provide a twice-a-day or a once-a-day formulation."
`
`and at page 6, line 29 to page 7, line 4:
`
`-3-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`Claim 71
`[Claim 1 ofKumar]
`
`abuse deterrent dosage form
`comprising:
`
`a. a core matrix
`
`comprising a blended
`mixture of:
`
`Supporting Disclosure
`USSN 10/214,412
`"The aversive agents of the present invention are preferably for
`use in connection with oral dosage forms including opioid
`analgesics, which provide valuable analgesia but which may be
`abused. This is particularly true for controlled release opioid
`analgesic products which have a large dose of opioid analgesic
`intended to be released over a period of time in each dosage unit.
`Drug abusers typically may take a controlled-release product and
`crush, shear, grind, chew, dissolve and/or heat, extract or
`otherwise damage the product so that the full contents of the
`dosage form become available for immediate absorption by
`injection, inhalation, and/or oral consumption."
`At page 6, line 29 to page 7, line 4:
`
`"The aversive agents of the present invention are preferably for
`use in connection with oral dosage forms including opioid
`analgesics, which provide valuable analgesia but which may be
`abused. This is particularly true for controlled release opioid
`analgesic products which have a large dose of opioid analgesic
`intended to be released over a period of time in each dosage unit.
`Drug abusers typically may take a controlled-release product and
`crush, shear, grind, chew, dissolve and/or heat, extract or
`otherwise damage the product so that the full contents of the
`dosage form become available for immediate absorption by
`injection, inhalation, and/or oral consumption."
`At page 16, lines 15-20:
`
`"The opioid analgesic formulation in combination with one or
`more aversive agents can be formulated as an immediate release
`formulation or controlled release oral formulation in any suitable
`tablet, coated tablet or multiparticulate formulation known to
`those skilled in the art. The controlled release dosage form may
`include a controlled release material which is incorporated into a
`matrix along with the opioid analgesic. In addition, the aversive
`agent may be separate from the matrix, or incorporated into the
`matrix."
`At page 24, line 32 to page 25, line 6:
`
`"In other embodiments of the invention, melt-extruded
`formulations are prepared without the inclusion of the opioid
`analgesic; one or more aversive agents; or mixtures thereof;
`which is added thereafter to the extrudate. Such formulations
`typically will have the opioid analgesic; one or more aversive
`agents; or mixtures thereof blended together with the extruded
`matrix material, and then the mixture would be tableted in order
`
`-4-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`Claim 71
`I Claim 1 of Kumar]
`
`(a) PEO
`
`having a molecular weight of
`from about 300,000 to about
`5,000,000;
`
`Supporting Disclosure
`USSN 10/214,412
`to provide a slow release formulation. Such formulations may be
`advantageous, for example, when the opioid analgesic; one or
`more aversive agents; or mixtures thereof included in the
`formulation is sensitive to temperatures needed for softening the
`hydrophobic material and/or the retardant material."
`At page 8, lines 23 to 33:
`
`"In certain embodiments of the present invention wherein the
`dosage form includes an aversive agent comprising a gelling
`agent, various gelling agents can be employed including, for
`example and without limitation, sugars or sugar derived alcohols,
`such as mannitol, sorbitol, and the like, starch and starch
`derivatives, cellulose derivatives, such as microcrystalline
`cellulose, sodium caboxymethyl cellulose, methylcellulose, ethyl
`cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and
`hydroxypropyl methylcellulose, attapulgites, bentonites,
`dextrins, alginates, carrageenan, gum tragacanth, gum acacia,
`guar gum, xanthan gum, pectin, gelatin, kaolin, lecithin,
`magnesium aluminum silicate, the carbomers and carbopols,
`polyvinylpyrrolidone, polyethylene glycol, polyethylene oxide,
`polyvinyl alcohol, silicon dioxide, surfactants, mixed
`surfactant/wetting agent systems, emulsifiers, other polymeric
`materials, and mixtures thereof, etc."
`At page 31, line 10 to page 32, line 10:
`
`"In certain embodiments, the bilayer core comprises a drug layer
`with opioid analgesic and a displacement or push layer
`optionally containing the one or more aversive agents. The one
`or more aversive agents may optionally be included in the drug
`layer instead of or in addition to being included in the push layer.
`In certain embodiments the drug layer may also comprise at least
`one polymer hydrogel. The polymer hydrogel may have an
`average molecular weight of between about 500 and about
`6,000,000. Examples of polymer hydro gels include but are not
`limited to a maltodextrin polymer comprising the formula (C6
`H120s)n .H20, wherein n is 3 to 7 ,500, and the maltodextrin
`polymer comprises a 500 to 1,250,000 number-average
`molecular weight; a poly(alkylene oxide) represented by, e.g., a
`poly( ethylene oxide) and a poly(propylene oxide) having a
`50,000 to 750,000 weight-average molecular weight, and more
`specifically represented by a poly( ethylene oxide) of at least one
`of 100,000, 200,000, 300,000 or 400,000 weight-average
`molecular weights; an alkali carboxyalkylcellulose, wherein the
`alkali is sodium or potassium, the alkyl is methyl, ethyl, propyl,
`
`-5-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`Claim 71
`[Claim 1 ofKumarl
`
`(b) magnesium stearate; and
`
`(c) oxycodone or a
`pharmaceutically acceptable
`salt thereof;
`
`Supporting Disclosure
`USSN 10/214,412
`or butyl of 10,000 to 175,000 weight-average molecular weight;
`and a copolymer of ethylene-acrylic acid, including methacrylic
`and ethacrylic acid of 10,000 to 500,000 number-average
`molecular weight.
`
`"In certain embodiments ofthe present invention, the delivery or
`push layer comprises an osmopolymer. Examples of an
`osmopolymer include but are not limited to a member selected
`from the group consisting of a polyalkylene oxide and a
`carboxyalkylcellulose. The polyalkylene oxide possesses a
`1,000,000 to 10,000,000 weight-average molecular weight. The
`polyalkylene oxide may be a member selected from the group
`consisting of polymethylene oxide, polyethylene oxide,
`polypropylene oxide, polyethylene oxide having a 1,000,000
`average molecular weight, polyethylene oxide comprising a
`5,000,000 average molecular weight, polyethylene oxide
`comprising a 7,000,000 average molecular weight, cross-linked
`polymethylene oxide possessing a 1,000,000 average molecular
`weight, and polypropylene oxide of 1,200,000 average molecular
`weight. Typical osmopolymer carboxyalkylcellulose comprises a
`member selected from the group consisting of alkali
`carboxyalkylcellulose, sodium carboxymethylcellulose,
`potassium carboxymethylcellulose, sodium
`carboxyethylcellulose, lithium carboxymethylcellulose, sodium
`carboxyethylcellulose, carboxyalkylhydroxyalkylcellulose,
`carboxymethylhydroxyethyl cellulose,
`carboxyethylhydroxyethylcellulose and
`carboxymethylhydroxypropylcellulose. The osmopolymers used
`for the displacement layer exhibit an osmotic pressure gradient
`across the semipermeable wall. The osmopolymers imbibe fluid
`into dosage form, thereby swelling and expanding as an osmotic
`hydrogel (also known as osmogel), whereby they push the
`contents of the drug layer from the osmotic dosage form."
`At page 34, lines 4-6:
`
`"In certain embodiments, the dosage form comprises a lubricant,
`which may be used during the manufacture of the dosage form to
`prevent sticking to die wall or punch faces. Examples of
`lubricants include but are not limited to magnesium stearate, .... "
`At page 10, line 31 to page 11, line 2:
`
`In certain preferred embodiments, the opioid agonist is selected
`from the group consisting of hydrocodone, morphine,
`hydromorphone, oxycodone, codeine, levorphanol, meperidine,
`
`-6-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`Claim 71
`fClaim 1 ofKumarl
`
`wherein the matrix is heated
`to melt at least a portion of
`the PEO included in the
`matrix; and
`
`b. PEG applied onto the core
`matrix
`
`Supporting Disclosure
`USSN 10/214,412
`methadone, oxymorphone, buprenorphine, fentanyl and
`derivatives thereof, dipipanone, heroin, tramadol, etorphine,
`dihydroetorphine, butorphanol, levorphanol, or salts thereof or
`mixtures thereof. In certain preferred embodiments, the opioid
`agonist is oxycodone or hydrocodone."; and
`
`see also, page 11, lines 8-1 0.
`At page 22, lines 14-20:
`
`"A sustained-release matrix can also be prepared by, e.g., melt-
`granulation or melt-extrusion techniques. Generally, melt-
`granulation techniques involve melting a normally solid
`hydrophobic binder material, e.g., a wax, and incorporating a
`powdered drug therein. To obtain a sustained release dosage
`form, it may be necessary to incorporate a hydrophobic
`sustained-release material, e.g. ethylcellulose or a water-
`insoluble acrylic polymer, into the molten wax hydrophobic
`binder material. Examples of sustained-release formulations
`prepared via melt-granulation techniques are found, e.g., in U.S.
`Pat. No. 4,861,598 [which is incorporated by reference in its
`entirety, see page 2, lines 16-17].";
`
`and at page 22, lines 28-32:
`
`"The preparation of a suitable melt-extruded matrix according to
`the present invention may, for example, include the steps of
`blending the opioid analgesic and at least one aversive agent,
`together with a sustained release material and preferably a binder
`material to obtain a homogeneous mixture. The homogeneous
`mixture is then heated to a temperature sufficient to at least
`soften the mixture sufficiently to extrude the same."
`PEG (polyethylene glycol) may be used as an aversive (gelling)
`agent, e.g., at page 8, lines 23-31 ("In certain embodiments of
`the present invention wherein the dosage form includes an
`aversive agent comprising a gelling agent, various gelling agents
`can be employed including, for example and without limitation, .
`. . polyethylene glycol, .... ");
`
`The dosage form may include one or more aversive agents, e.g.,
`at page 9, lines 28-29 ("In certain embodiments, the dosage form
`may include one or more of the aforementioned aversive
`agents."); and
`
`The dosage form may be coated with a sustained release coating
`
`-7-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`Claim 71
`[Claim 1 ofKumar]
`
`wherein the dosage form
`provides extended release of
`the drug.
`
`Supporting Disclosure
`USSN 10/214,412
`that includes one or more of the aversive agents, e.g., at page 24,
`lines 13-18 ("Optionally, the sustained-release matrix
`multiparticulate systems, tablets, or capsules can be coated with
`a sustained release coating such as the sustained release coatings
`described herein. * * * The coating can optionally contain one
`or more of the aversive agents.").
`
`Alternatively, the support for "PEG applied onto the core
`matrix" can be found at page 17, line 31; page 18, line 22 and
`Example 1 at page 40, line 14 to page 41, line 4, which disclose
`and exemplify a film coating comprising Opadry® which is a
`commercially available film coating that contains polyethylene
`glycol as a component.
`
`At page 6, lines 4-9:
`
`"The term "sustained release" is defined for purposes of the
`present invention as the release of the opioid analgesic from the
`oral dosage form at such a rate that blood (e.g., plasma)
`concentrations (levels) are maintained within the therapeutic
`range but below toxic levels over an extended period of time,
`e.g., from about 12 to about 24 hours as compared to an
`immediate release product. Preferably the sustained release is
`sufficient to provide a twice-a-day or a once-a-day
`formulation.";
`
`and at page 6, line 29 to page 7, line 1 :
`
`"The aversive agents of the present invention are preferably for
`use in connection with oral dosage forms including opioid
`analgesics, which provide valuable analgesia but which may be
`abused. This is particularly true for controlled release opioid
`analgesic products which have a large dose of opioid analgesic
`intended to be released over a period of time in each dosage
`unit."
`
`The foregoing claim chart shows that all the limitations of new claim 71 (and claim 1 of
`Kumar) are found in the instant application. Thus, the claim is fully supported in this application
`in accordance with 35 USC § 112.
`Applicants claim priority in the instant application as follows:
`
`-8-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`This application is a continuation of U.S. Patent Application No.
`13/349,449, filed January 12,2012, which is a continuation of U.S. Patent
`Application No. 12/653,115, filed December 8, 2009, which is a continuation of
`U.S. Patent Application No. 10/214,412, filed August 6, 2002, which claims the
`benefit ofU.S. Provisional Application No. 60/310,534, filed August 6, 2001.
`
`Since the instant application claims priority to its earliest utility application through a
`series of continuation applications, the instant specification and newly introduced claim 71 are
`entitled to at least the benefit of the earliest related utility application filing date, i.e., August 6,
`2002. Thus, the instant application is entitled to an earlier priority relative to the Kumar patent.
`Furthermore, as Applicants will subsequently show as necessary, instant claim 71 is also
`entitled to priority at least back to the filing date of its corresponding related provisional
`application, from which priority is also expressly claimed, i.e., August 6, 2001.
`In contrast, the earliest that Kumar can claim priority is the filing date of its earliest related
`application, i.e., November 26, 2003. Thus, instant claim 71 is entitled to a priority date preceding
`Kumar's earliest priority date by more than two years. Applicants are thus entitled to priority of
`invention relative to Kumar; and should be accorded senior status in any corresponding
`interference.
`
`No Common Ownership
`There is no common ownership between the instant application and the Kumar patent.
`
`-9-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`

`

`Attorney Docket No. 21076-181
`Supplemental Amendment
`
`III. Conclusion
`
`In view of the foregoing, Applicants respectfully request entry and substantive
`consideration of the claim introduced herein. An early and favorable action is earnestly solicited.
`If the Examiner perceives any impediments to a prompt formal notification of allowability,
`Applicants encourage the Examiner to telephone the undersigned at (973)597-2404. The
`undersigned also may be contacted via e-mail at rparadiso@lowenstein.com. Such informal
`communication will expedite disposal of the instant case. All formal correspondence should be
`directed to our address listed below.
`
`AUTHORIZATION
`The Commissioner is hereby authorized to charge any fees that may be required, or credit
`any overpayment, to Deposit Account No. 50-1358.
`
`Respectfully submitted,
`Lowenstein Sandler PC
`Attorneys for Applicants
`
`s/Robert J. Paradiso/
`By: Robert J. Paradiso
`Attorney for Applicants
`Registration No. 41,240
`
`Date: January 23, 2013
`
`DOCKET ADMINISTRATOR
`LOWENSTEIN SANDLER PC
`65 Livingston A venue
`Roseland, NJ 07068
`General Tel.: 973-579-2500
`
`-10-
`
`KASHIV1053
`IPR of Patent No. 9,492,393
`
`