IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Appl. No.
`Applicant
`Filed
`TC/A.U.
`Examiner
`
`: 13/617,138
`: Roberto VILLA et al.
`
`: 14 September 2012
`71615
`: Susan T. Tran
`
`Docket No.
`Customer No.
`Confirmation No.
`
`: 3850-125
`: 06449
`: 7811
`
`AMENDMENT AND RESPONSE TO ADVISORY ACTION
`
`MAIL STOP AF
`Commissionerfor Patents
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`
`Dear Sir:
`
`In further response to the Final Office Action dated 22 August 2013 and in response to
`
`the Advisory Action dated 18 October 2013, please further amendthis application as follows.
`
`Amendments to the Claims begin on page 2 of this paper. The amendments to the
`
`claims include those made in the Amendmentand Response filed on 26 September 2013.
`
`Remarksbegin on page 4 of this paper immediately after the Amendments to the Claims.
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`Application No.: 13/617,138
`Attorney Docket No. 3850-125
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`AMENDMENTS TO THE CLAIMS
`
`This listing of claims will replaceall prior versions andlistings of claims in the
`
`application.
`
`Listing of Claims
`
`1. (Currently Amended)
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`A controlled release oral pharmaceutical composition consisting
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`essentially of:
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`(1) a tablet core comprising consisting essentially of:
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`a) budesonide in an amounteffective to treat intestinal inflammatory disease; and
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`b) a macroscopically homogeneous composition comprising at least one
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`lipophilic excipient, at least one amphiphilic excipient, and at least one hydrogel-forming
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`hydrophilic excipient other than a gum, wherein said budesonideis dispersed in said
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`macroscopically homogeneous composition; and
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`(2) a coating on said tablet core, said coating comprising consisting essentially of a
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`gastro-resistant film.
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`2. (Canceled)
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`3. (Previously Presented) A controlled release oral pharmaceutical composition according to
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`claim 1, wherein said at least one hydrogel-forming hydrophilic excipient comprisesatleast one
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`hydroxyalkyl! cellulose.
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`4, (Canceled)
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`5. (Currently Amended) A controlled release oral pharmaceutical composition according to
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`claim 1, wherein said gastro-resistant film eemprises consists essentially of at least one
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`methacrylic acid polymer.
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`Application No.: 13/617,138
`Attorney Docket No. 3850-125
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`6, (Previously Presented) A controlled release oral pharmaceutical composition according to
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`claim 5, wherein said at least one hydrogel-forming hydrophilic excipient comprisesatleast one
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`hydroxyalkyl cellulose.
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`7-8. (Canceled)
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`9. (Previously Presented) A controlled release oral pharmaceutical composition according to
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`claim 1, wherein saidat least one lipophilic excipient comprises stearic acid or magnesium
`stearate.
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`10, (Previously Presented) A controlled release oral pharmaceutical composition according to
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`claim 9, wherein said at least one hydrogel-forming hydrophilic excipient comprises at least one
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`hydroxyalky! cellulose.
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`11, (Previously Presented) A controlled release oral pharmaceutical composition accordingto
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`claim |, wherein said at least one amphiphilic excipient compriseslecithin.
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`12. (Previously Presented) A controlled release oral pharmaceutical composition according to
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`claim 11, wherein said at least one hydrogel-forming hydrophilic excipient comprises at least one
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`hydroxyalkyl cellulose.
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`13. (Previously Presented) A controlled release oral pharmaceutical composition according to
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`claim 11, wherein said at least one lipophilic excipient comprises stearic acid or magnesium
`stearate.
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`Application No.: 13/617,138
`Attorney Docket No. 3850-125
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`REMARKS
`
`Status of Claims
`
`Claims 1, 3, 5, 6, and 9-13, as amended, are currently pending and under examination.
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`Claims 2, 4, 7 and 8 were previously canceled. Claims | and 5 are currently amended. Support
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`for the amendments can be found throughoutthe specification, for example, at paragraphs
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`[0047], [0051], [0052], [0080], and [0082] in the substitute Specification. Applicants note that
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`the amendmentto claim 5 and the amendmentto the tablet core language in claim 1 are newly
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`made in the paper. Applicants submit that these amendments do not constitute new matter, raise
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`new issues, or require further searching. Thus, their entry and allowance are requested.
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`Examiner Interview
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`The undersigned thanks the Examiner for the courtesies shown during the telephone
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`interview held on 18 October 2013. During the interview, the undersigned discussed the
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`possibility of amending claim 5 to change the language to “consisting essentially of’ in order to
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`overcome the continued rejection of the claims. The Examinerindicated that this amendment
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`might overcomethe rejection as made with respect to the coating, but she would need to review
`the references. The Examiner then raised a further issue with the claims in the context of the
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`outstanding rejections. This issue concerned the language “comprising” as used with respect to
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`the tablet core. The Examinersaid that she believes that this language does not exclude a
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`coating. Asa basis for this belief, the Examiner explained that there are manytypesof tablet
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`cores including those made by coating a particle, such as with a drug layer and with further
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`layers. Thus, she believes that this comprising language for the tablet core allows other layers,
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`such as a coating layer of Lerner.
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`Rejection under 35 U.S.C. § 102(a) over Lerner
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`The Examinerhas rejected claims 1, 5 and 6, as allegedly anticipated by U.S. Patent No.
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`5,840,332 to Lemer et al. (“Lerner”). Final Office Action at 2-3.
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`Claim | as amendedis patentable over Lerner. Claim 1 specifies a controlled release oral
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`pharmaceutical composition that consists essentially of a table core and a coating. Thetable core
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`Application No.: 13/617,138
`Attorney Docket No, 3850-125
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`consists essentially of budesonide and a macroscopically homogencous composition. This
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`macroscopically homogeneous composition comprises (i) at least one lipophilic excipient,(ii) at
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`least one amphiphilic excipient and(iii) at least one hydrogel-forming hydrophilic excipient
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`other than a gum. The budesonide is dispersed in the macroscopically homogeneous
`
`composition.
`
`According to the Examiner,
`
`Lernerteaches a gastrointestinal drug delivery system comprising an active
`core surround by a coating. See abstract. Core in a form of a matrix tablet
`comprises drug and combinationsof pectin, calcium pectinate,
`hydroxypropylmethylcellulose, microcrystalline cellulose, lactose, starch,
`calcium phosphate, and polyvinylpyrrolidone (column 6, lines 9-10; and
`column 8, lines 35-64). Coating comprises methacrylic acid. See column 9,
`lines 28-65, Drug includes budesonidesuitablefor irritable bowel syndrome
`and thelike (column 6, lines 44-57; and column 12, line 43).
`Final Office Action at 3.
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`Applicant submits that Lerner does not teach a tablet core that consists essentially of a
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`macroscopically homogeneous composition comprising “(i) at least one lipophilic excipient,
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`(ii) at least one amphiphilic excipient and(iii) at least one hydrogel-forming hydrophilic
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`excipient other than a gum.” Thus, Lerner does not describe all of the elements of the
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`macroscopically homogeneous composition and hence does not describe all of the elements of
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`the tablet core. Therefore, Lerner does not anticipate the subject matter of amendedclaim |. For
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`these reasonsalone,the rejection under 35 U.S.C. § 102(a) in view of Lerner should be
`withdrawn.
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`Furthermore, Applicants have amendedclaim|to recite the transitional phrase
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`“consisting essentially of’ in part (2) with respect to the coating. Thatis, part (2) now recites “a
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`coating onsaid tablet core, said coating consisting essentially of a gastro-resistant film.” In
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`addition, Applicants have amendedclaim 5 to recite the transitional phrase “consisting
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`essentially of’ with respect to the gastro-resistant film in order to make the language consistent
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`It will not be in dispute that “consisting essentially of” is
`with the language of amended claim 1.
`used to exclude from the claim that which affects the basic and novel characteristics of the
`
`claimed invention. See MPEP 2163(1])(A)(1). The amendment to claim 5 makesit clear that the
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`Application No.: 13/617,138
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`“consisting essentially of’ language used in part (2) is used to exclude from the claim that which
`affects the basic and novel characteristics of the claimed invention.
`
`Byreciting “consisting essentially of” for the coating, Applicants wish to clarify that a
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`basic and novel characteristic of amended claim | is a coating consisting essentially of a gastric
`
`resistant film, in which the coating is on a tablet core. See, e.g., substitute Specification,
`
`paragraph [0053].
`
`In addition, by reciting “consisting essentially of” for the tablet core, Applicants wishto
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`clarify that a basic and novel characteristic of amended claim | is a tablet core consisting
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`essentially of budesonide and a macroscopically homogeneous composition comprising at least
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`one lipophilic excipient, at least onc amphiphilic excipient andat least one hydrogel-forming
`
`hydrophilic excipient other than a gum in which the budesonide is dispersed in the
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`macroscopically homogencous composition, See, e.g., substitute Specification, paragraph
`
`[0052].
`
`Lerner is directed to a gastrointestinal delivery system in which a core is “surrounded by
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`a water-insolubleor relatively water-insoluble coating material in whicha particulate water-
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`insoluble material is embedded.’ Lerner, Abstract, Il. 1-4; see also col. 6, Il. 11-16; col 10,Il. 2-
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`11 and 63-67. In the gastrointestinaltract, that particulate matter “takes up liquid, thus forming
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`channels interconnecting the drug containing core with the outside of the delivery device.”
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`Lerner, Abstract, lI. 5-8; see also col. 6, Il. 11-25. More specifically, the particulates embedded
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`in the coating swell, thereby creating channels through whichfluid can passinto the core and
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`dissolve the active ingredient contained in the core. The solubilized active ingredient then passes
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`through the channels, thereby controlling the release of the active ingredient. See e.g., Lerner at
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`col. 6, Il. 11-14; col. 8, Il. 66-67; col. 6, Il. 11-14. Therefore, the Lerner coatingis not a coating
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`that is meant to dissolve in the gastrointestinal tract, but instead remains intact to control the
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`release of the active ingredient in the core. Lerner, col. 10, ll. 6-11.
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`In contrast, the claimed controlled release oral pharmaceutical compositionsconsist
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`essentially of a tablet core and a coating on the tablet core, the coating consisting essentially of a
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`gastro-resistantfilm. See, e.g., substitute Specification, paragraph [0053] and Example | at
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`paragraphs [0078]-[0079]. One of ordinary skill in the art reading the specification would
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`understand that a gastro-resistant coating is designed to prevent early release of the drug in the
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`Application No.: 13/617,138
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`stomach butdissolves when the dosage form reachesthe desired target region ofthe
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`gastrointestinaltract, such as the colon. As such, one ofordinary skill in the art would
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`understand that the dosage formsdisclosed in Lernerare very different than the presently
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`claimed controlled release oral pharmaceutical compositions in which a coreis coated with a
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`gastro-resistant film that is designed to dissolve when the dosage form reachesthe target region
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`of the gastrointestinal tract. Therefore, Lerner does not anticipate the subject matter of amended
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`claim |. For these additional reasons, the rejection under 35 U.S.C. § 102(a) in view of Lerner
`should be withdrawn.
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`In the Advisory Action, the Examiner argued that the language “comprising”in claim 5
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`which depends from claim | requires the interpretation of claim | to include other components
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`that which affect the basic and novel characteristics of the claimed invention. Applicants submit
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`that the amendmentof claim 5 to use the language “consisting essentially of’ does not support
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`such aninterpretation of claim |. Thatis, it is now that the language of claim | excludesthe
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`presenceofparticulates in the coating as taught and required by Lerner. Therefore, Lerner does
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`not anticipate the subject matter of amended claim 1. For these additional reasons, the rejection
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`under 35 U.S.C. § 102(a) in view of Lerner should be withdrawn.
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`In addition, one ofordinary skill in the art reading the specification would also
`
`understandthat the tablet core is designed to be a macroscopically homogeneous composition of
`
`the recited excipients in which the budesonide is dispersed. See, ¢.g., substitute Specification,
`
`paragraph [0052]. This macroscopically homogeneous composition is different than a core made
`
`of layers or that includes a layer. Therefore, Lerner does not anticipate the subject matter of
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`amended claim |. For these additional reasons, the rejection under 35 U.S.C. § 102(a) in view of
`Lerner should be withdrawn.
`
`Rejection under 35 U.S.C, § 103(a) over Lerner in view of Savastano
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`The Examinerhas rejected claims 1, 3, 5, 6, and 9-13 as allegedly unpatentable over U.S.
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`Patent No. 5,840,332 to Lerneret al. (“Lerner”) in view of U.S. Patent No. 5,681,584 to
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`Savastano (“Savastano”). Final Office Actionat 3-4.
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`Claim | as amendedis patentable over Lerner in view of Savastano. As discussedin
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`detail above, Applicants have amendedclaim | to recite the transitional phrase “consisting
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`Application No.: 13/617,138
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`essentially of” in part (2) with respect to the coating. Thatis, part (2) nowrecites “a coating on
`
`said tablet core, said coating consisting essentially of a gastro-resistant film.” The presently
`
`claimed controlled release oral dosage forms are very different than those disclosed in the Lerner
`and Savastano references.
`
`As discussed earlier, Lerneris directed to a gastrointestinal delivery system in which a
`
`core is “surrounded by a water-insoluble or relatively water-insoluble coating material in which a
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`particulate water-insoluble material is embedded.” Lerner, Abstract,ll. 1-4; see also col. 6,Il.
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`11-16, col 10, Il. 2-11 and 63-67.
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`In the gastrointestinal tract, that particulate matter “takes up
`
`liquid, thus forming channels interconnecting the drug containing core with the outside of the
`
`delivery device.” Lerner, Abstract, ll. 5-8, see also col. 6, Il. 11-25. More specifically. the
`
`particulates embedded in the coating swell, thereby creating channels through which fluid can
`
`pass into the core and dissolve the active ingredient contained in the core. The solubilized active
`
`ingredient then passes through the channels, thereby controlling the release of the active
`
`ingredient. See e.g., Lernerat col. 6, ll. 11-14; col. 8, ll. 66-67; col. 6, Il. 11-14. Therefore, the
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`Lerner coating is not a coating meantto dissolve in the gastrointestinal tract, but instead remains
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`intact to control the release of the active ingredient in the core. Lerner, col. 10, Il. 6-11.
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`Therefore, one of ordinary skill in the art would not seck to modify the teachings of the Lerner
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`reference in orderto arrive at the presently claimed controlled release oral pharmaceutical
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`compositions.
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`Further, the addition of the Savastano reference doesnot cure the deficiencies of Lerner.
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`In particular, the dosage forms taught by Savastano require both a delay jacket and a semi-
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`permeable membrane surroundingthe tablet core to control the release of the active ingredient
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`and so are very different than the presently claimed controlled release oral pharmaceutical
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`compositions. See e.g., Savastano, abstract, and col. 5, lines 31-42.
`
`Hence, the “consisting essentially of” language used in amended claim 1 and in claim 5,
`
`completely distinguishes over the very different teachings of Lerner and Savastano. Therefore,
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`the combination of Lerner and Savastano would not have rendered obvious the subject matter of
`
`amended claim 1, For these reasons, the rejection under 35 U.S.C. § 103(a) over Lernerin view
`of Savastano should be withdrawn.
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`Application No.: 13/617,138
`Attorney Docket No. 3850-125
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`In addition, one of ordinary skill in the art reading the specification would also
`
`understandthat the tablet core is designed to be a macroscopically homogencous composition of
`
`the recited excipients in which the budesonideis dispersed. See, e.g., substitute Specification,
`
`paragraph [0052]. This macroscopically homogeneous composition is different than a core made
`
`of layers or that includes a layer. Therefore, the combination of Lerner and Savastano would not
`
`have rendered obvious the subject matter of amended claim 1. For these additional reasons, the
`
`rejection under 35 U.S.C. § 103(a) over Lerner in view of Savastano should be withdrawn.
`
`Conclusion
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`Althoughprincipally directed to amended claim 1, the remarks above apply with equal
`
`force to all the dependent claims. Consequently, in view of the above amendments and remarks,
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`it is submitted that the claimssatisfy the requirements of the patent statutes and are patentable
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`overthe prior art of record. Reconsideration of this application andearly notice of allowanceis
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`requested. The Examineris invited to telephone the undersignedif it will assist in expediting the
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`prosecution and allowanceof the instant application.
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`In the event that any additional fee is required in connection with the filing of this
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`Amendment and Response, the Commissionerfor Patents is authorized to charge the amount of
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`such fee to Rothwell, Figg, Ernst and Manbeck P.C. Deposit Account No. 02-2135.
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`Respectfully submitted,
`
`Dated: 21 February 2014
`
`By
`
`(Jeffrey L. Ihnen/
`Jeffrey L. Ihnen
`Registration No. 28,957
`Attorney for Applicants
`607 14th Street, N.W., Suite 800
`Washington, D.C. 20005
`Phone: 202-783-6040
`Fax:
`202-783-6031
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