DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`PATENT
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`Hans Wim Pictcr Vcrmccrsch
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`Application No.: 12/536,807
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`Filing Date: August 6, 2009
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`Confirmation No.: 4088
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`Group Art Unit: 1625
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`Examiner: Celia C. Chang
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`For: PSEUDOPOLYMORPHIC FORMS OF A HIV PROTEASE INHIBITOR
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`Mail Stop AF
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`Dear Commissioner:
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`REPLY PURSUANT TO 37 CFR § 1.116
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`In response to the Official Action dated May 22, 2012, reconsideration is respectfully requested
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`in view of the amendments and/or remarks as indicated below:
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`[]
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`[]
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`[]
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`[]
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`[]
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`Amendments to the Specification begin on page of this paper.
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`Amendments to the Claims are reflected in the listing of the claims which begins on
`page 2 of this paper.
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`Amendments to the Drawings begin on page
`attached replacement sheet.
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`Remarks begin on page 5 of this paper.
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`of this paper and include an
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`The Commissioner is hereby authorized to charge any fee deficiency, charge any
`additional fees, or credit any overpayment of fees, associated with this application in
`connection with this filing, or any future filing, submitted to the U.S. Patent and
`Trademark Office during the pendency of this application, to Deposit Account No. 23-
`3050.
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`Page 1 of 10
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`Lupin Ex. 1012 (Page 1 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`PATENT
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`This listing of claims will replace all prior versions, and listings, of claims in the application.
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`Listing of Claims:
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`Claims 1- 14 Cancelled
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`15. (Previously Presented) A hydrate of the compound (3R,3aS,6aR)-hexahydrofuro [2,3-b]
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`furan-3-yl ( 1 S,2R)-3- [ [(4-aminophenyl) sulfonyl] (isobutyl) amino]-l-benzyl-2-
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`hydroxypropylcarbamate in which the ratio of the compound to water is about 1:0.5 to
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`about 1:3.
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`16. (Previously Presented) A hydrate having the formula:
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`O
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`OH
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`¯ H20
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`17. (Previously Presented) A composition comprising a hydrate of the compound
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`(3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl)sulfonyl]
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`(isobutyl) amino]-l-benzyl-2-hydroxypropylcarbamate, in which the ratio of compound to
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`water is about 1:0.5 to about 1:3, and an inert carrier.
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`18. (Canceled)
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`19. (Canceled)
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`20. (Previously Presented) The composition of claim 17 wherein the inert carrier is a
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`pharmaceutically acceptable carrier.
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`21. (Previously Presented) The composition of claim 20 wherein the pharmaceutically
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`acceptable carrier is a solid inert carrier.
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`Page 2 of 10
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`Lupin Ex. 1012 (Page 2 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`22. (Canceled)
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`PATENT
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`23. (Previously Presented) A composition comprising a hydrate having the formula:
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`O
`
`H
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`¯ H20
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`OH
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`and an inert carrier.
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`24.
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`(Previously Presented) The composition of claim 23 wherein the inert carrier is a
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`pharmaceutically acceptable carrier.
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`25.
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`(Previously Presented) The composition of claim 24 wherein the pharmaceutically
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`acceptable carrier is a solid inert carrier.
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`26. (Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
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`water is about 1:1 to about 1:2.
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`27.
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`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
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`water is about 1:0.5.
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`28.
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`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
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`water is about 1:1.
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`29.
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`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
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`water is about 1:2.
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`30.
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`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
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`water is about 1:3.
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`31.
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`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
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`water is about 1:1 to about 1:2.
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`Page 3 of 10
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`Lupin Ex. 1012 (Page 3 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
`
`PATENT
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`32.
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`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
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`water is about 1:0.5.
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`33.
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`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
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`water is about 1:1.
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`34.
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`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
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`water is about 1:2.
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`35.
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`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
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`water is about 1:3.
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`36.
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`(Previously Presented) The composition of claim 17 further comprising amorphous
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`(3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl)sulfonyl]
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`(isobutyl) amino]-l-benzyl-2-hydroxypropylcarbamate.
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`Page 4 of 10
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`Lupin Ex. 1012 (Page 4 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`PATENT
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`Claims 15-17, 20, 21, and 23-36 are pending. No claim amendments have been made.
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`REMARKS
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`Rejection under 35 U.S.C. § 112, Second Paragraph
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`Claims 15-17, 20, 21, and 23-36 stand rejected under 35 U.S.C. § 112, second paragraph,
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`as allegedly indefinite. The basis for this rejection appears to be an alleged inconsistency
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`between the fact that claim 15 is directed to "A hydrate" yet embraces multiple hydrates that
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`each have a ratio of (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-
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`aminophenyl) sulfonyl] (isobutyl) amino]-l-benzyl-2- hydroxypropylcarbamate to water that is
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`within the specified range. However, it is well established that an applicant may present a patent
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`claim that (as in claim 15) uses the definite article "a" to embrace each of multiple embodiments
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`of an invention. The Office Action also alleges that it is unclear "how many hydrates" are within
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`the scope of claim 15 (Office Action at page 2), but there is no requirement under the patent laws
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`for a claim to specify how many embodiments it includes.
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`Claim 16 has been alleged to make claim 15 confusing, but this rejection also lacks basis.
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`Claim 16 specifies that the ratio of compound to water be 1 : 1, which is well within the range
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`(i.e., 1:0.5 to about 1:3) that is recited in claim 15.
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`Accordingly, Applicants request that the rejection for alleged indefiniteness be
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`reconsidered and withdrawn.
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`Rejection under 35 U.S.C. § 112, First Paragraph
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`Written Description
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`Claims 15-17, 20, 21, and 23-36 stand rejected under 35 U.S.C. § 112, first paragraph,
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`because Applicants’ disclosure allegedly does not provide adequate support for the ratio that is
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`recited in claim 15. Applicants request reconsideration of this rejection because their disclosure
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`reasonably conveys to those skilled in the art that Applicants were in possession of the claimed
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`subject matter.
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`Page 5 of 10
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`Lupin Ex. 1012 (Page 5 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`PATENT
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`A patent application need not describe a claimed invention in ipsis verbis to comply with
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`the written description requirement. "[A]ll that is required is that it reasonably convey to persons
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`skilled in the art that, as of the filing date thereof, the inventor had possession of the subject
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`matter later claimed by him." In re Edwards’, 568 F.2d 1349, 1351-1352 (C.C.P.A.
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`1978)(citations omitted). To determine whether a specification contains adequate written
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`description of the claimed subject matter, the critical question, is not whether literal description
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`of the claimed subject matter is present in the specification but, rather, whether review of the
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`specification would convey the claimed subject matter to those having skill in the art. Id. In
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`rejecting a claim for lack of written description, the examiner carries the burden of providing
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`reasons why a person skilled in the art at the time the application was filed would not have
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`recognized that the inventor was in possession of the invention as claimed in view of the
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`disclosure of the application as filed (see MPEP §2163.04).
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`Adequate written description is provided if a skilled artisan, upon review of a patent
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`specification in light of the properties and features of what is described, would envision the
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`claimed subject matter. In re Smythe, 480 F.2d 1376, 1384 (C.C.P.A. 1973). In Smythe, the
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`original specification and claims described a segmentation medium as air or other gas. Claims
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`directed to fluid as the segmentation medium were later introduced into the application. The
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`Court of Customs and Patent Appeals held that adequate written description of fluid as the
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`segmentation medium existed in the specification because the essential properties and features of
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`the segmentation medium, as described in the specification, defined a fluid. Id. at 1384. As the
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`court observed, because the broader concept of using "inert fluid" would naturally occur to one
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`skilled in the art from reading appellants’ description, there was "no basis for denying appellants
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`the claims which recite the segmentizing medium broadly as an ’inert fluid.’" Id. at 1384.
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`The same logic applied in In re Smythe mandates a finding that Applicants’ claims are
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`adequately described. "In particular, the ratio may range from about 0.2 to about 3 molecules of
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`solvent per 1 molecule of compound." Id. at page 7, lines 22-23. "IT]he ratio may range from
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`about 1 to about 2 molecules of solvent per 1 molecule of compound." Id. at page 7, lines 23-24.
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`"[P]referably the ratio is 1 molecule of solvent per 1 molecule of compound." Id. at page 7,
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`Page 6 of 10
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`Lupin Ex. 1012 (Page 6 of 10)
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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`PATENT
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`lines 25-26. This description reasonably conveys to persons skilled in the art that Applicants had
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`possession of the claimed subject matter.
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`The specification provides additional disclosure that further conveys to the skilled person
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`that Applicants had possession of the claimed subject matter as of the filing date. For example,
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`hydrates of the claimed compound (referred to throughout the specification as "Form B") were
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`made using several methods. For instance, Example 2 describes the preparation of a mixture of
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`Form B and Form D (the acetonate). Form B was also prepared by subjecting Form A (the
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`ethanolate) to adsorption-desorption analysis. See, e.g., Example 7. Indeed, the Form B material
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`that was tested in Example 4 was obtained by adsorption-desorption of a Form A sample, which
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`explains why some ethanol was lost during the thermogravimetric analysis.
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`Still further disclosure in the specification demonstrates means for preparing hydrates
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`within the scope of the present claims. The thermogravimetric analysis set forth in Example 4
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`demonstrates preparation of the Form B monohydrate; a water weight loss of 3.4% was
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`observed, which is consistent with Table 10’s prediction for the monohydrate. Example 11 (and
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`related Table 18) describes the thermogravimetric analysis of other fractions of Form B. The
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`weight changes reported in Table 18 are consistent with that of the monohydrate (3.56%, 3.13%)
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`and dihydrate (5.65%, 5.91%). Example 12, in turn, describes adsorption and desorption
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`experiments of another sample of Form B. These experiments involved subjecting the sample to
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`different humidities and recording the weight change as a function of relative humidity. The
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`weight changes of the sample are consistent with what would be observed for the hemihydrate
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`(1.2%) and the dihydrate (5.6% and 6.8%).
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`Not only does the specification describe actual samples of the hemi-, mono-, and di-
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`hydrate of the claimed compound, it teaches that hydrates can be prepared by subjecting Form A
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`or Form B to adsorption-desorption, that is, by subjecting Form A or Form B to various relative
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`humidities. See, e.g., Examples 7 and 12. As such, the claimed hydrates could readily be formed
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`by subjecting a sample to various relative humidities.
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`Given this disclosure, there is no basis for the Office’s contention that the claims lack
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`written description. In addition, Applicants have reviewed the CAS indexing documents
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`Page 7 of 10
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`Lupin Ex. 1012 (Page 7 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
`
`PATENT
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`identified by the Office. Not only is it unclear where in these documents the ratio of the claimed
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`compound to water is identified as "being of an indefinite ratio" (Office Action at 3), it is unclear
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`how the cited documents have any relevance to the claimed invention, the scope of the present
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`specification, or the inventors’ possession of the invention at the time of filing. Withdrawal of
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`the rejection is requested.
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`Enablement
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`Claims 15-17.20, 21, and 23-36 stand rejected under 35 U.S.C. § 112, first paragraph, as
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`allegedly not enabled. According to the Office Action, "the disclosure does not contain
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`sufficient information to enable one skilled in the pertinent art for recovery of [specific crystal
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`preparations]." (Office Action at 4). Applicants request reconsideration and withdrawal of this
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`rejection because the evidence of record indicates that Applicants’ disclosure would have
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`enabled those skilled in the art to practice the claimed inventions.
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`Enablement must be evaluated against the claimed subject matter. MPEP 2164.08.
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`"Accordingly, the first analytical step requires that the examiner determine exactly what subject
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`matter is encompassed by the claims." Id.
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`The pending claims are directed to, among other things, hydrates of the claimed
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`compound. As defined in the specification, "hydrates" are "substances that are formed by adding
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`water molecules." (Specification at page 6, lines 6-7).~
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`Compositions wherein water molecules have been added to the claimed compound are
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`clearly enabled by the specification, as originally filed. The specification sets forth several
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`examples describing the claimed compound and water. As noted above, Example 2 describes the
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`preparation of a mixture of Form D (acetonate) and Form B. As stated in Example 2, the starting
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`compound was stirred in acetone and heated until the compound dissolved. Water was then
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`added and the solution was cooled. The resulting crystals were a mixture of the acetonate (Form
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`The Examiner, rather than interpreting the claims in light of the specification, has alleged that the claims
`"are drawn to polymorphic crystalline forms of" the claimed compound (Office Action at page 4). The claims must
`be interpreted in light of the specification and the Specification as originally filed clearly establishes that the
`Applicants had possession of the invention where water molecules are added to the claimed compound.
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`Page 8 of 10
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`Lupin Ex. 1012 (Page 8 of 10)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
`
`PATENT
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`D) and the hydrate (Form B). Various Form B hydrates were also formed by subjecting Form A
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`to adsorption!desorption tests, as described at Example 7. Form B hydrates were also formed by
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`subjecting a sample of Form B to adsorption!desorption. See, e.g., Example 12.
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`Because there is no evidence indicating that this disclosure would have been insufficient
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`for those skilled in the art to make the claimed hydrates (i.e. substances formed by adding water
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`molecules to the claimed compound) the rejection for alleged lack of enablement should be
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`withdrawn.
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`The Office alleges that the claims are not enabled because some of Applicants’
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`experimental examples indicate that ethanol in also included in certain hydrates of the invention.
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`But the claims are directed to compositions to which water molecules have been added to the
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`claimed compound; the claims don’t exclude the addition of other solvents. Therefore, the
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`presence of ethanol in certain of the examples does not support the Office’s allegations ofnon-
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`enablement.
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`The Office further alleges that it is unclear from Example 2 how form B was made.
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`Example 2 clearly recites a process by which a mixture of form B and form D were prepared.
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`The fact that Example 2 describes preparation of a mixture falls far short of demonstrating that
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`the claimed invention is not enabled.
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`Accordingly, the rejections under Section 112 should be reconsidered and withdrawn
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`Conclusion
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`The pending claims are in condition for allowance. An early and favorable notice to that
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`effect is, therefore, earnestly solicited.
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`Page 9 of 10
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`Lupin Ex. 1012 (Page 9 of 10)
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`PATENT
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`Joseph Lucci
`Registration No. 33,307
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`Stephanie A. Barbosa
`Registration No. 51,430
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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: May 22, 2012
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`Date: July 20, 2012
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`Woodcock Washburn LLP
`Cira Centre
`2929 Arch Street, 12th Floor
`Philadelphia, PA 19104-2891
`Telephone: (215) 568-3100
`Facsimile: (215) 568-3439
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`Page 10 of 10
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`Lupin Ex. 1012 (Page 10 of 10)