`
`Exhibit 1017
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`File History of the ‘688 Patent, Amendment
`6/20/2014
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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
`
`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 / Prioritized Examination
`Commissioner for Patents
`P.O. Box 1450
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`Alexandria, VA 22313-1450
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`AMENDMENT AND RESPONSE TO OFFICE ACTION
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`Dear Madam:
`
`In reply to the Office Action mailed June 5, 2014, Applicant respectfully requests
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`reconsideration of this application in View of the following remarks.
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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 5.
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`Ex 1017 ME1 18392263V.1
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`MycoNovo, Inc.
`Foxhill Opportunity Fund, L.P.
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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 granulated mesalamine formulation comprising
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`four capsules each comprising 0.375 g of granulated mesalamine once per day in the morning,
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`with—o1= without food, 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;
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`the granulated mesalamine formulation is not administered with antacids; and
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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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`(Previously Presented) 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 the terminal 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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`ME1 18392263v.1
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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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`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 with or without
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`food or without regard to meals.
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`21.
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`(Cancelled)
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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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`(Previously Presented) The method of claim 24, further comprising assessing the
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`subject’s renal function at one 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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`ME1 18392263v.1
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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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`(Previously Presented) 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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`(Cancelled)
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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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`(Currently Amended) 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 granulated mesalamine formulation comprising four
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`capsules each comprising 0.375 g of granulated mesalamine once per day in the morning, with
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`or without food, 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;
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`the granulated mesalamine formulation is not administered with antacids; and
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`wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon.
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`ME1 18392263v.1
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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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`I.
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`Examiner Interview
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`REMARKS
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`Applicant would like to thank the Examiner for the courtesy of the telephonic interview
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`conducted on June 19, 2014 in which the obviousness rejection of record was discussed. No
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`agreement was reached.
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`II.
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`Status of the Claims
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`As presented above, Claims 1 and 74 are amended to define that the granulated
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`mesalamine formulation is administered without food. Support for this amendment can be found
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`e.g., on page 4, lines 31-35 of the application as filed. No new matter is added. Claims 14, 17-
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`20, 23-31, 70, 73, and 74 remain pending.
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`II.
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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 remain rejected under pre-AIA 35 U.S.C. §
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`103(a) as allegedly being unpatentable over the Salix article as evidenced by Meyeroff in view
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`of Endonurse and optionally further in view of Netdoctor. Office Action at 2-12. Claim 31 also
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`remains rejected under pre-AIA 35 U.S.C. § 103 (a) as allegedly being unpatentable over the
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`Salix article as evidenced by Meyeroff in view of Endonurse and optionally further in view of
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`Netdoctor, and further in view of Fischkoff. E. at 10-12. Applicant continues to disagree for at
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`least the reasons of record and for at least the additional reasons that follow.
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`However, solely in the interest of expediting prosecution, and in no way acquiescing to
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`the validity of the Examiner’s rejection, Applicant has amended claims 1 and 74 to indicate that
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`the granulated mesalamine is administered to the subject without food.
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`As discussed with the Examiner, unlike other 5-mesalamine drugs available at the time of
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`the invention, Applicant has demonstrated that the claimed methods are equally safe and
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`effective when granulated mesalamine is administered to a subject without food.
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`The Salix article cited by the Examiner is completely silent as to the administration of the
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`granulated mesalamine with or without food. The press release does not disclose Applicant’s
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`discovery that the oral mesalamine formulation was equally effective when administered with or
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`ME1 18392263v.1
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`5
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`Docket No.: 122184—02804
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`Application No.: 12/573,081
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`without food. Based on the cited art, one having ordinary skill in the art would have been unable
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`to come to a conclusion as to the efficacy of the mesalamine formulation when administered
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`without food. Thus, at the time of filing, one having ordinary skill in the art would have to look
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`elsewhere for guidance as to the administration of oral mesalamine to a subject with or without
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`food.
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`At the time of the invention, there were at least two other oral mesalamine formulations
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`approved by the FDA. As indicated above, the pending claims are directed to methods of
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`administering a delayed and extended—release gal mesalamine formulation. The mesalamine
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`formulation most similar to the one in the pending claims is Lialda®. Lialda® is a delayed and
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`extended—release oral meslamine tablet that was approved for inducing the remission of active,
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`mild to moderate ulcerative colitis in 1987. Specifically, Lialda® is a tablet coated with a pH
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`dependent polymer film, which breaks down at or above pH 6.8, typically in the terminal ileum.
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`The tablet core contains mesalamine with hydrophilic and lipophilic excipients and provides for
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`extended release of mesalamine. Lialda® is administered as “two to four 1.2 g tablets taken
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`once daily with food.” See e.g., the sections on page 1 and 2 of the Lialda® prescribing
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`information (a copy of which is submitted herewith) entitled “Dosing and Administaration”.
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`Specifically, the Dosing and Administration section on page 2 sets forth that “[t]he
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`recommended dosage for the induction of remission in adult patients with active, mild to
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`moderate ulcerative colitis is two to four 1.2 g tablets taken once daily with a meal for a total
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`daily dose of 2.4 g or 4.8 g. The recommended dosage for the_maintenance of remission is two
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`1.2 g tablets taken once daily with a meal for a total_daily dose of 2.4 g. Emphasis added.
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`Another oral mesalamine formulation available at the time of the invention is Pentasa®.
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`Pentasa® is a controlled release mesalamine formulation that was approved for administration to
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`subjects having mild to moderate ulcerative colitis in 1993. Unlike granulated mesalamine,
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`Pentasa® is not a controlled and extended—release formulation. The Pentasa® label is silent in
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`regards to administration relative to food.
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`As indicated above, the cited art does not teach or suggest administering granulated oral
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`mesalamine with or without food. In fact, the press release is silent as to the need to administer
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`granulated mesalamine with or without food. At the time of the invention, one of ordinary skill
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`in the art would look to the teachings of the most similar formulation to determine if
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`administration with food is required. In this case, the skilled artisan would look to the teachings
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`ME1 18392263v.1
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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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`related to Lialda® and be of the opinion that it would be necessary to administer a delayed and
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`extended—release oral mesalamine formulation with food.
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`However, Applicant’s specification and examples set forth the results of a clinical trial
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`showing that there is no decrease in efficacy when granulated mesalamine is administered
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`without food.
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`As set forth in Example 1, Applicant determined that granulated mesalamine can be
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`taken with or without food. Specifically, Example 1 sets forth:
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`[t]he effect of a high fat meal intake on absorption of mesalamine granules (the
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`same granules contained in granulated mesalamine formulation capsules) was
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`evaluated in 30 healthy subjects. Subjects received 1.6 g of mesalamine granules
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`in sachet (2 x 0.8 g) following an overnight fast or a high—fat meal in a crossover
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`study. Under fed conditions, tmax for both 5—ASA and N—Ac—5—ASA was
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`prolonged by 4 and 2 hours, respectively. A high fat meal did not affect Cmax for
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`5—ASA, but a 27% increase in the cumulative urinary excretion of 5—ASA was
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`observed with a high fat meal. The overall extent of absorption of N—Ac—5—ASA
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`was not affected by a high fat meal. As granulated mesalamine formulation and
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`mesalamine granules in sachet were bioequivalent, granulated mesalamine
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`formulation can be taken without regard to food.
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`Additionally, Example 4 sets forth the results of another pharmacokinetics study. This
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`study demonstrates that
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`the effect of food intake on 5—ASA absorption was evaluated. Healthy subjects
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`received 1.6 g of granulated mesalamine (2 x 0.8 g) following an overnight fast or
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`a high—fat meal in a crossover study. Tmax for both mesalamine and N—Ac—5—ASA
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`was prolonged following a high—fat meal. Based on an 80%: 125% rule for
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`untransformed data, the plasma Cmax for mesalamine and N—Ac—5—ASA were
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`equivalent in fed and fasted conditions. A slight increase was seen in mesalamine
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`AUCO_inf and AUC0_1aS[ (11% and 16%, respectively) following a high—fat meal.
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`The overall rate and extent of absorption of mesalamine and its N-acetyl
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`metabolite were not affected by a high—fat meal.
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`ME1 18392263v.1
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`Docket No.: 122184-02804
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`Application No.: 12/573,081
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`Accordingly, based on the clinical trial results detailed above, Applicant demonstrated
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`that, unlike the closest mesalamine formulation available in the art, the claimed granulated
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`mesalamine extended release oral formulations can be administered without food.
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`The cited art, including the Salix Press Release and the secondary reference cited by the
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`Examiner do not teach or suggest that the claimed formulation of granulated mesalamine could
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`be effectively administered in the absence. In fact, each of the cited references is completely
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`silent as to the administration of mesalamine with food.
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`For at least these reasons, one of skill in the art would not have found the claimed
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`methods obvious in view of the cited references and the knowledge available with regard to
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`other delayed and extended-release £1 mesalamine formulations at the time that the instant
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`application was filed. Applicant respectfully requests reconsideration and withdrawal of the
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`foregoing rejection.
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`IV.
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`Final Remarks
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`Applicant respectfully requests 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 Applicant’s 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) 449-6509.
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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: 20 June 2014
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`Respectfully submitted,
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`/Jonathan M. Sparks/
`Electronic signature:
`Jonathan Sparks, Ph.D.
`Registration No.: 53,624
`McCarter & English, LLP
`265 Franklin Street
`
`Boston, MA 02110
`
`(617)-449-6509 (Tel)
`(617)-607-9200 (Fax)
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`ME1 18392263v.1