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`Exhibit 1016
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`File History of the ‘688 Patent, Amendment
`5/9/2014
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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)
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`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.
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`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 AFTER FINAL
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`Dear Madam:
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`In reply to the final Office Action mailed March 27, 2014, Applicants respectfully
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`request reconsideration of this application in View of the following remarks. This response
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`accompanies a Request for Continued Examination and fulfills the requirement of a submission
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`under 37 C.F.R. § 1.114. A Certification and Request for Prioritized Examination under 37
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`C.F.R. § 1.102(e) together with the appropriate fee payment is also filed concurrently herewith.
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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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`ME1 17828307V.1
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`MycoNovo, Inc.
`Foxhill Opportunity Fund, L.P.
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`Ex 1016
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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 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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`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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`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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`Docket No.: 122184—02804
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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, E
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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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`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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`As presented above, Claims 1 and 74 are amended to define that the granulated
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`mesalamine formulation is administered with or without food. Support for this amendment can
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`be found e.g., on page 4, lines 31-35 of the application as filed. No new matter is added. Claims
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`14, 17-20, 23-31, 70, 73, and 74 remain pending.
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`II. Withdrawn Rejections
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`Applicants acknowledge the indication that the previously applied § 102(b) rejection has
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`been withdrawn from record. Office Action at 2.
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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 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 under pre-AIA 35 U.S.C. § 103(a) as allegedly being unpatentable over
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`the Salix article as evidenced by Meyeroff in view of Endonurse and optionally further in view
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`of Netdoctor, and further in view of Fischkoff. E. at 10-12. Applicants continue to disagree for
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`at least the reasons of record and for at least the additional reasons that follow.
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`Applicants previously argued that Meyeroff, which is relied upon in the present rejection,
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`contradicts the disclosure of both the Salix article and Endonurse because Meyeroff teaches
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`(with supporting objective/clinical evidence) that lower dosages of 5-ASAs (e.g., meslamine) are
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`insufficient to achieve remission of inflammatory bowel disease, such as ulcerative colitis.
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`Because Meyeroff published after the disclosures of the Salix article and Endonurse, Applicants
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`argued that one of skill in the art at the time of the instant disclosure would not have been
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`motivated to administer the claimed 1.5 total gram a day dosage because Meyereoff teaches,
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`with clinical evidence, that this low dosage would not be effective for achieving remission.
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`In reply, the present Office Action indicates that such arguments are not persuasive
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`because Meyeroff was not relied upon for administration/dosing elements, but rather relied upon
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`as evidentiary evidence to demonstrate that one skill in the art would have realized that
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`Docket No.: 122184—02804
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`Application No.: 12/573,081
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`remaining—relapse free would have been defined as a DAI score of 0 or 1. Office Action at 12. In
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`other words, the present Office Action ignores the remaining teachings of Meyeroff (and
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`Applicants’ previous arguments) on the basis that such teachings did not form the basis of the
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`initial rejection. This, respectfully, is improper.
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`The law makes it clear that a prior art reference must be considered in its entirety, i.e., as
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`a whole, including portions that would lead away from the claimed invention. MPEP §
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`2141.02(VI). That is, the conflicting disclosures of Meyeroff cannot be ignored. Moreover, it is
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`also made clear that where the teachings of a prior art reference conflict, the Examiner must
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`weigh the suggestive power of each reference to suggest sol u tions to one of ordinary skill in the
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`art, considering the degree to which one reference might accurately discredit another.
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`927 F.2d 588, 18 USPQ2d 1089 (Fed. Cir. 1991) and MPEE’ § 2l43.2()l(ll). in other
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`words, Applicants believe that it is the Examiner°s burden to explain why the subsequent
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`reference of ‘fvileyerofjf, which provides actual clinical data to show that lower dosages of 5-ASA
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`are insufficient to achieve remission, would not have suggested to the skilled artisan that higher
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`dosages of meslamine would have been required to maintain remission. Applicants submit that
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`this standard has not been met in the instant Office Action. Rather, Applicants previous
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`arguments have been improperly dismissed.
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`For at least this reason, Applicants submit that a prima facie case of obviousness has not
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`been established.
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`While in no way acquiescing to the validity of this or any other previous rejections of
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`record, and solely to advance prosecution, Claim 14 now recites a method of maintaining the
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`remission of ulcerative colitis in a subject comprising administering to the subject a granulated
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`mesalamine formulation comprising four capsules each comprising 0.375 g of granulated
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`mesalamine once per day in the morning, with or without food. Claim 74 has been amended in a
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`similar fashion.
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`The Examiner previously argued that daily dosage could be administered at any of the
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`three times of day (morning, afternoon or evening). Thus, morning is an easy choice as one of
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`three times, but this is only true if you assume that administration is concurrent with or related to
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`ingestion of a meal. However, as amended, the claims recite administration, once a day in the
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`morning, with or withoutfood. The granulated mesalamine formulation currently claimed does
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`Docket No.: 122184-02804
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`Application No.: 12/573,081
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`need to be administered with food (i.e., at the same time as the subject has a meal). In fact,
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`unlike other 5—ASA prodrugs and as detailed in the specification, the claimed granulated
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`mesalamine product has been shown to be equally effective when administered to a subject with
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`or without food.
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`Therefore, if the granulated mesalamine is administered without regard to meals (i.e.,
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`with or without food), administration can take place anytime within the twenty four hour period,
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`not merely at the three times of day specified by the Examiner.
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`For at least these additional reasons, one of skill in the art would not have found the
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`claimed methods obvious in view of the cited references at the time that the instant application
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`was filed. Applicants respectfully request reconsideration and withdrawal of the foregoing
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`rejection.
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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) 449-6509.
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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: May 9, 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
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`Boston, MA 02110
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`(617)-449-6509 (Tel)
`(617)-607-9200 (Fax)
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