`
`Exhibit 1020
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`‘688 Patent File History (“FH688”),
`Amendment 10/8/2013
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`

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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`Docket No.: 122184—02804
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`(PATENT)
`
`In re Patent Application of:
`William Forbes
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`Application No.: 12/573,081
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`Confirmation No.: 5308
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`Filed: October 2, 2009
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`Art Unit: 1611
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`For: COMPOSITIONS AND METHODS FOR
`TREATMENT OF BOWEL DISEASES WITH
`GRANULATED MESALAMINE
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`Examiner: FRAZIER, BARBARA S.
`
`MS Amendment / RCE
`Commissioner for Patents
`P.O. Box 1450
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`Alexandria, VA 22313-1450
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`AMENDMENT AND RESPONSE UNDER 37 C.F.R.
`
`1.116
`
`Dear Madam:
`
`In reply to the final Office Action mailed July 31, 2013, Applicants respectfully request
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`reconsideration of this application in View of the following amendments and remarks. This
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`response accompanies a Request for Continued Examination and fulfills the requirements of a
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`submission under 37. C.F.R. § 1.114.
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`Amendments to the Claims begin on page 2 of this paper.
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`Remarks follow the Amendments to the Claims and begin on page 6.
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`M E1 16472858V.1
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`MycoNovo, Inc.
`Foxhill Opportunity Fund, L.P.
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`EX 1020
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`

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`Docket No.: 122184—02804
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`Application No.: 12/573,081
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`AMENDMENTS TO THE CLAIMS
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`This listing of claims will replace all prior Versions, and listing of claims, in this
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`application.
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`Listing of Claims:
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`1-13. (Cancelled)
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`14.
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`(Currently Amended) A method of maintaining the remission of ulcerative colitis in a
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`subject comprising administering to the subject a single 1.5 gram dose of a granulated
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`mesalamine formulation once per day, wherein:
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`said method maintains remission of ulcerative colitis in a subject for a period of at least 6
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`months of treatment;
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`remission is defined as a DAI score of 0 or 1; [[and]]
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`the granulated mesalamine formulation is not administered with antacidsgfld
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`wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon.
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`15.
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`(Cancelled)
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`16.
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`(Cancelled)
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`17.
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`(Previously Presented) The method of claim 14, wherein the granulated mesalamine
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`formulation is a delayed and extended release formulation.
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`18.
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`(Currently Amended) The method of claim 17, wherein delayed and extended release
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`comprises first releasing mesalamine in the ileum and continuing to release mesalamine
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`throughout th_eterminal ileum and colon.
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`19.
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`(Original) The method of claim 14, wherein the granulated mesalamine formulation is
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`administered for the maintenance of remission of ulcerative colitis in subjects 18 years of age
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`and older.
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`Docket No.: 122184—02804
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`Application No.: 12/573,081
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`20.
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`(Previously Presented) The method of claim 14, wherein the granulated mesalamine
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`formulation comprises four capsules administered once per day in the morning, afternoon or
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`evening with or without food or without regard to meals.
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`21.
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`(Currently Amended) The method of claim 14, wherein the granulated mesalamine
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`formulation comprises four capsules administered per day in the morning, with or without food.
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`22.
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`(Cancelled)
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`23.
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`(Previously Presented) The method of claim 14, further comprising advising the subject
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`that subjects having hypersensitivity to salicylates, aminosalicylates, or any component of the
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`granulated mesalamine formulation should not be administered the granulated mesalamine
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`formulation.
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`24.
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`(Original) The method of claim 14, further comprising advising the subject that when
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`being administered granulated mesalamine formulation renal impairment may occur.
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`25.
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`(Currently Amended) The method of claim 24, further comprising assessing the
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`subject’s renal function Qone or more of the following: at the beginning of treatment, before
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`initiating therapy, or periodically during therapy.
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`26.
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`(Original) The method of claim 14, further comprising advising the subject that acute
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`exacerbation of colitis symptoms can occur.
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`27.
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`(Original) The method of claim 14, further comprising advising the subject that the
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`granulated mesalamine formulation should be used with caution in subjects with renal disease.
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`28.
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`(Original) The method of claim 14, further comprising monitoring the blood cell counts
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`in geriatric subjects being administered the granulated mesalamine formulation.
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`29.
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`(Original) The method of claim 14, further comprising advising the subject that there are
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`adverse reactions associated with administration of the granulated mesalamine formulation.
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`Docket No.: 122184—02804
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`Application No.: 12/573,081
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`30.
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`(Currently Amended) The method of claim 29, wherein the adverse reactions comprise
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`one or more of headache, diarrhea, upper abdominal pain, nausea, nasopharyngitis, flu or flu—like
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`illness, and sinusitis.
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`31.
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`(Original) The method of claim 14, further comprising advising the subject that the
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`granulated mesalamine formulation is not expected to inhibit the metabolism of drugs that are
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`substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4.
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`32-69. (Cancelled)
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`70.
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`(Previously presented) The method of claim 14, further comprising selecting a subject
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`with a DAI score of 0 or 1 for maintaining remission of ulcerative colitis with granulated
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`mesalamine.
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`71.
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`(Cancelled)
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`72.
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`(Previously Presented) The method of claim 21, wherein the four capsules each
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`comprise 0.375 g granulated mesalamine.
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`73.
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`(Previously Presented) The method of claim 14, wherein the mesalamine comprised in
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`the formulation is released over approximately 7 hours.
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`74.
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`(Previously Presented) A method of maintaining the remission of ulcerative colitis in a
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`subject comprising advising the subject that granulated mesalamine should not be taken with
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`antacids and administering to the subject a single 1.5 gram dose of a granulated mesalamine
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`formulation once per day, wherein:
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`said method maintains remission of ulcerative colitis in a subject for a period of at least 6
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`months of treatment;
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`remission is defined as a DAI score of 0 or 1; [[and]]
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`the granulated mesalamine formulation is not administered with antacidsgfld
`
`wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon.
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`Docket No.: 122184-02804
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`Application No.: 12/573,081
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`1.
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`Status of the Claims
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`REMARKS
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`Claims 14 and 74 are amended to recite “wherein 85% to 90% of mesalamine reaches the
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`terminal ileum and colon.” Support for the amendment can be found, for example, at page 12,
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`lines 1-6 and lines 16-18 of the specification as filed. Claims 21, 25 and 30 are amended to
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`address minor informalities in the claim language.
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`No new matter is added by way of these amendments. Upon entry of this amendment,
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`Claims 14, 17-21, 23-31, 70, and 72-74 are pending.
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`II.
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`Rejection under 35 U.S.C. § 102
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`Claims 14, 17-19, 70 and 73 have been rejected under pre-AIA 35 U.S.C. §102(b) for
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`allegedly being anticipated by a Salix article (from Drugs.com [online], published September 5,
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`2007, hereinafter “the Salix article”) as evidenced by Karlstadt Meyeroff et al. (U.S. Patent
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`Publication No. 2010/0035850, hereinafter “Meyeroff”). Office Action at 2-5. Applicants
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`respectfully disagree.
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`The pending claims are directed to methods of maintaining the remission of ulcerative
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`colitis in a subject comprising administering to the subject a single 1.5 gram dose of granulated
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`mesalamine formulation once per day, wherein, inter alia, the formulation is not administered
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`with antacids and 85% to 90% of mesalamine reaches the terminal ileum and colon.
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`The Salix article describes a Phase III registration trial to evaluate the safety and efficacy of a
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`granulated mesalamine product that was under development at the time the article was published
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`for maintaining remission of patients with ulcerative colitis. While the cited reference indicates
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`that test subjects were dosed once-a-day with 1.5 grams of granulated mesalamine, Applicants
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`respectfully submit that it does not explicitly teach that the formulation is to be administered
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`without antacids. The Office Action asserts that “since [the Salix article] only discloses
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`administration of mesalamine, it inherently follows that the mesalamine is not administered with
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`other agents, such as antacids.” (See e.g., Office Action, page 5.) However, the disclosure of the
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`Salix article is generally directed to the results of the clinical trial; there is no information
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`provided about the details of the clinical trial protocol, such as whether or not the mesalamine
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`formulation was administered with or without other agents, let alone a specific teaching that the
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`formulation be administered without antacids.
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`Docket No.: 122184-02804
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`Application No.: 12/573,081
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`For example, the mesalamine formulation may have been administered with another
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`agent which did not significantly affect the outcome of the results. However, the skilled artisan,
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`in reading and understanding the Salix article, would not be able to glean any such information
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`regarding whether or not another agent was co—administered with the formulation. The Salix
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`article does not provide any level of detail about administration of the formulation of the clinical
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`trial except for the fact that the formulation was a once—a—day formulation of granulated
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`mesalamine administered as a 1.5 gram dose. In an attempt to link administration of the
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`mesalamine formulation with the recited feature of not administering the formulation with
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`antacids, one would have to rely on the teachings of the instant application. Such an attempt,
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`however, is impermissible hindsight. Accordingly, Applicants respectfully maintain that the
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`Salix article does not teach the claimed feature of administration of the mesalamine formulation
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`without antacids.
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`Furthermore, the Salix article does not teach the additional recited feature that 85% to
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`90% of mesalamine reaches the terminal ileum and colon. Rather, the Salix article generally
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`discloses that the administered formulation is a delayed and extended release formulation. The
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`Salix article provides no information for how the drug is distributed throughout the targeted
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`therapeutic region, nor is there any teaching that the drug would specifically be distributed in
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`this manner. A person of skill in the art would not have been able to appreciate the recited
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`features of the claims based on the generic description provided in the Salix article.
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`That is, the instant application discloses a granulated mesalamine composition with a pH
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`dependent coating that dissolves at pH 6 or greater and a polymer matrix core which distributes
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`the mesalamine slowly and uniformly throughout the lumen of the terminal ileum and colon.
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`The instant application also provides pharmacokinetic information and release profile
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`information that support the recited feature that 85% to 90% of mesalamine reaches the terminal
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`ileum and colon. See Applicants specification at, for example, Examples 1, 4 and 6; page 12,
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`lines 1-21; page 14, lines 19-27; page 33, lines 6-13; page 40, lines 16-18. Accordingly,
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`Applicants respectfully submit that the Salix article does not provide sufficient technical detail
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`or information to enable the skilled artisan to provide a method as claimed.
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`In view of the foregoing, Applicants submit that the cited reference does not teach each
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`and every feature of the claimed subject matter. As such, the claims are novel over the Salix
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`article. Withdrawal of the rejection is respectfully requested.
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`6
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`Docket No.: 122184-02804
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`Application No.: 12/573,081
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`III.
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`Rejections under 35 U.S.C. § 103
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`Claims 14, 17-20, 23-30, 70, 73 and 74 have been rejected under pre-AIA 35 U.S.C.
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`§103 (a) for allegedly being unpatentable over the Salix article as evidenced by Meyeroff and
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`optionally in View of an Asacol (Mesalazine) article available online at NetDoctor (hereinafter
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`“NetDoctor”). Office Action at 6-11. Additionally, Claims 21 and 72 have been rejected under
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`pre-AIA 35 U.S.C. §103(a) as allegedly being unpatentable over the Salix article as evidenced
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`by Meyeroff optionally in view of Netdoctor and further in view of Endonurse. E. at 11-12.
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`Further, Claim 31 has been rejected under pre-AIA 35 U.S.C. §103(a) as allegedly being
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`unpatentable over the Salix article as evidenced by Meyeroff optionally in view of Netdoctor and
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`further in view of Fischkoff et al. (U.S. Patent Publication No. 2007/0243184, hereinafter
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`“Fischkoff”). E. at 12-13. Applicants respectfully disagree.
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`As discussed above, the claimed subject matter is directed to methods of maintaining the
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`remission of ulcerative colitis in a subject comprising administering to the subject a single 1.5
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`gram dose of granulated mesalamine formulation once per day, wherein, inter alia, th_e
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`formulation is not administered with antacids and 85% to 90% of mesalamine reaches the
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`terminal ileum and colon.
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`The deficiencies of the Salix article have been addressed above. There is no teaching or
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`suggestion in the Salix article that the formulation is n_ot administered with antacids, nor is there
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`any teaching or suggestion that 85% to 90% of mesalamine reaches the terminal ileum and colon
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`in the claimed methods.
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`NetDoctor is relied upon for its disclosure that one should not take indigestion remedies
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`(antacids) at the same time of day as Asacol MR tablets due to the special enteric coating on the
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`Asacol tablets. The Office Action asserts that NetDoctor teaches mesalamine which has an
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`enteric coating that allows the Asacol tablets to pass through the stomach and be released in the
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`intestine and asserts that the claimed formulation has the same release profile, as does the
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`formulation of Salix. (See Office Action, p. 16.) Applicants respectfully disagree with the
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`implication that “the claimed formulation has the same release profile” as the Asacol tablets.
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`While the Asacol tablets of NetDoctor and the formulation of the instant application both contain
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`mesalamine, the release profile of the instant application is distinct from that of the Asacol
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`tablets due to its polymer matrix core, which provides a mechanism by which mesalamine is
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`uniformly and slowly released and distributed in the lumen of the colon. In contrast, NetDoctor
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`7
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`Docket No.: 122184—02804
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`Application No.: 12/573,081
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`merely discloses that the Asacol tablets have an enteric coating; however, there is nothing
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`further in NetDoctor to indicate that extended release of mesalamine takes place throughout the
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`colon.
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`Furthermore, NetDoctor does not remedy the deficiencies of the Salix article with respect
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`to the requirement of the claimed subject matter that 85% to 90% of mesalamine reach the
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`terminal ileum and colon. NetDoctor provides a disclosure of the recommended usage of Asacol
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`suppositories, foam enema and MR tablets. However, there is no teaching or suggestion in
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`NetDoctor to provide a method of maintaining remission of ulcerative colitis by administering a
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`granulated mesalamine formulation wherein 85% to 90% of mesalamine reaches the recited
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`targeted therapeutic region.
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`Neither of Endonurse or Fischkoff repairs the deficiencies of the Salix article and
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`NetDoctor. Endonurse is relied upon for its teaching that granulated mesalamine can be dosed
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`as four 375 mg tablets once daily. Fischkoff is relied upon for its disclosure that the incidence of
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`enterocolitis induced by an immunostimulatory therapeutic antibody can be reduced by
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`administering a non—absorbable steroid in combination with a salicylate. An exemplary non-
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`absorbable steroid is Entocort EC® (budesonide), which is extensively metabolized by the
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`cytochrome P450 system. However, neither of Endonurse or Fischkoff teach or suggest
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`administration of the formulation without antacids, nor does either reference teach or suggest the
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`recited feature that 85% to 90% of mesalamine reaches the terminal ileum and colon.
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`Accordingly, in view of the foregoing, Applicants respectfully submit that the claims are
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`patentable over the combination of cited references. Reconsideration and withdrawal of the
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`rejection under this section is respectfully requested.
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`IV.
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`Final Remarks
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`Applicants respectfully request entry of the above amendment, favorable reconsideration,
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`of this application, and the timely allowance of the pending claims. If a telephone conversation
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`with Applicants’ agent would help expedite the prosecution of the above—identified application,
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`the Examiner is urged to call the undersigned agent at (617) 449-6585.
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`Docket No.: 122184-02804
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`Application No.: 12/573,081
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`Please charge any fee(s) required for entry of this response, and any and all additional
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`fee(s) to our Deposit Account No. 50-4876, under Docket No. 122184-02804, from which the
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`undersigned is authorized to draw.
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`Dated: October 8, 2013
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`Respectfully submitted,
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`/Michael J. DeGrazia/
`Electronic signature:
`Michael J. DeGrazia, Ph.D.
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`Registration No.: 68,901
`McCarter & English, LLP
`265 Franklin Street
`
`Boston, MA 02110
`
`(617)-449-6585 (Tel)
`(617)-607-9200 (Fax)
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`ME1 16472858v.1