DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`Hans Wim Peter Vermeersch
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`Confirmation No.: 4088
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`Application No.: 12/536,807
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`Group Art Unit: 1625
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`Filing Date: August 6, 2009
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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 Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
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`REPLY PURSUANT TO 37 CFR § 1.111
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`In response to the Official Action dated September 12, 2011, reconsideration is respectfully
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`requested 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 8
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`Lupin Ex. 1010 (Page 1 of 8)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
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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. (Currently Amended) 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 1:31:1.
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`16. (Currently Amended) A hydrate~,olvatc having the formula:
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`OH
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`¯ H20
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`17. (Currently Amended) A composition comprising a[[an]] 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 1:31:1, 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. (Currently Amended) The composition of claim [[ 19]] 20 wherein the pharmaceutically
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`acceptable carrier is a solid inert carrier.
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`22. (Canceled)
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`Page 2 of 8
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`Lupin Ex. 1010 (Page 2 of 8)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
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`23. (New) A composition comprising a hydrate having the formula:
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`O
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`H
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`¯ H20
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`OH
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`and an inert carder.
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`24.
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`(New) The composition of claim 23 wherein the inert carder is a pharmaceutically
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`acceptable carder.
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`25. (New) The composition of claim 24 wherein the pharmaceutically acceptable carder is a
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`solid inert carrier.
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`26.
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`(New) The hydrate of claim 15 wherein the ratio of the compound to water is about 1 : 1
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`to about 1:2.
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`27.
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`(New) The hydrate of claim 15 wherein the ratio of the compound to water is about
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`1:0.5.
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`28. (New)
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`The hydrate of claim 15 wherein the ratio of the compound to water is about 1 : 1.
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`29. (New)
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`The hydrate of claim 15 wherein the ratio of the compound to water is about 1:2.
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`30. (New)
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`The hydrate of claim 15 wherein the ratio of the compound to water is about 1:3.
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`31. (New)
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`The composition of claim 17 wherein the ratio of the compound to water is about
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`1:1 to
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`about 1:2.
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`32.
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`(New) The composition of claim 17 wherein the ratio of the compound to water is about
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`1:0.5.
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`33.
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`(New) The composition of claim 17 wherein the ratio of the compound to water is about
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`1:1.
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`34.
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`(New) The composition of claim 17 wherein the ratio of the compound to water is about
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`1:2.
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`Page 3 of 8
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`Lupin Ex. 1010 (Page 3 of 8)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
`
`35. (New) The composition of claim 17 wherein the ratio of the compound to water is about
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`1:3.
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`36. (New) The composition of claim 17 further comprising amorphous (3R,3aS,6aR)-
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`hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl)
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`amino]-l-benzyl-2-hydroxypropylcarbamate.
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`Page 4 of 8
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`Lupin Ex. 1010 (Page 4 of 8)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
`
`REMARKS
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`Claims 15 and 17 have been amended to correct minor typographical errors and to recite
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`that the ratio of compound to water is from about 1:0.5 to about 1:3. Support for the
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`amendments can be found throughout the specification, for example, at Example 4, Table 10,
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`Example 11, Table 18, and Example 12.
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`Claim 16 has been amended to recite a hydrate having the claimed formula
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`Claims 23-36 are new. Claim 23 recites a composition comprising a hydrate and an inert
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`carrier. Claims 24 and 25 depend from claim 23. Applicants note that claims 23 and 24 include
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`subject matter from claims 18 and 19, now canceled. Claims 26-30 depend from claim 15 and
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`recite a ratio of compound to water. Similarly, claims 31-36 depend from claim 17 and recited a
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`ratio of compound to water.
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`No new matter has been added.
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`Rejection under 35 U.S.C. § 112, Second Paragraph
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`Claims 15-22 stand rejected under 35 U.S.C. § 112, second paragraph, as allegedly
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`indefinite. The Office alleges that it is unclear whether the product of claim 15 is the same as
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`that of claim 16, but it is clear that claim 16 is of narrower scope than claim 15. Claim 15 recites
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`a hydrate of the compound (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 in which the ratio
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`of the compound to water is about 1:0.5 to about 1:3. Claim 16, however, recites a hydrate in
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`which there is a 1:1 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 and water. Thus,
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`the relative scope of these claims is clear.
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`The Office also alleges that it is unclear whether the composition of claim 17 is the same
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`as that of claim 18. Amended claim 17 is directed to a composition in which the ratio of the
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`recited compound to water is about 1:0.5 to about 1:3. Claim 23, which replaces claim 18,
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`recites a chemical formula depicting a 1:1 ratio of the compound and water, and an inert carrier.
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`Thus, claim 23 clearly is narrower than claim 17.
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`Applicants accordingly request withdrawal of these rejections.
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`Page 5 of 8
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`Lupin Ex. 1010 (Page 5 of 8)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
`
`Rejection under 35 U.S.C. § 112, Fourth Paragraph
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`Claims 19 and 21 stand rejected under 35 U.S.C. § 112, fourth paragraph, as allegedly
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`being of improper dependent form. Claim 19 has been canceled and replaced by new claim 24.
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`Claim 21 has been amended to depend from claim 20. Applicants assert that the amended claims
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`are in proper dependent form and request withdrawal of the rejection.
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`Rejection under 35 U.S.C. § 112, First Paragraph
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`Claims 15-22 stand rejected under 35 U.S.C. § 112, first paragraph, as allegedly not
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`complying with the written description requirement with respect to whether Applicants have
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`possession of a monohydrate of the claimed compound. The Office, however, has failed to take
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`into consideration the entirety of Applicants’ disclosure, noting only the disclosure provided at
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`page 23 of the Specification. When the entirety of Applicants’ disclosure is considered,
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`including the specification, figures, and examples, it is clear that adequate written description has
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`been provided, not only for the monohydrate, but for hydrates comprising the claimed ratios of
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`compound to water.
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`As the specification makes clear, hydrates of the claimed compound (referred to
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`throughout the specification as "Form B") were made using several methods. For instance,
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`Example 2 describes the preparation of a mixture of Form B and Form D (the acetonate). Form
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`B was also prepared by subjecting Form A (the ethanolate) to adsorption-desorption analysis.
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`See, e.g., Example 7. Indeed, the Form B material that was tested in Example 4 was obtained by
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`adsorption-desorption of a Form A sample, which explains why some ethanol was lost during the
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`thermogravimetric analysis.
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`Additional disclosure relating to the claimed subject matter is provided in Table 10,
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`which sets forth expected thermogravimetric mass losses for different forms of the claimed
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`compound. That is, Table 10 sets forth the weight percent of solvent that each of the recited
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`forms would be expected to lose. Thus, as shown in Table 10, the hemihydrate (1:0.5 ratio of
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`compound to water) would be expected to exhibit a mass loss of about 1.6%; the monohydrate
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`(1:1 ratio of compound to water) would be expected to exhibit a mass loss of about 3.2%; the
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`Page 6 of 8
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`Lupin Ex. 1010 (Page 6 of 8)
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`

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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
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`dihydrate (1:2 ratio of compound to water) would be expected to exhibit a mass loss of about
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`6.2%; and the trihydrate (1:3 ratio of compound to water) would be expected to exhibit a mass
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`loss of about 9.0%.
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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 the claims lack written
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`description. Withdrawal of the rejecton therefore is requested.
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`Claims 15-22 stand rejected under 35 U.S.C. § 112, first paragraph, as allegedly not
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`enabled with respect to the preparation of the claimed hydrates. However, there is no reason to
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`believe that those skilled in the art, having read Applicants’ considerable disclosure relating to
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`preparation of such hydrates would be unable to practice the claimed inventions.
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`As noted above, Example 2 describes the preparation of a mixture of Form D (acetonate)
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`and Form B. As stated in Example 2, the starting compound was stirred in acetone and heated
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`Page 7 of 8
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`Lupin Ex. 1010 (Page 7 of 8)
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`DOCKET NO.: TIBO-0063
`Application No.: 12/536,807
`Office Action Dated: September 12, 2011
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`until the compound dissolved. Water was then added and the solution was cooled. The resulting
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`crystals were a mixture of the acetonate (Form D) and the hydrate (Form B). Various Form B
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`hydrates were also formed by subjecting Form A to adsorption!desorption tests, as described at
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`Example 7. Form B hydrates were also formed by subjecting a sample of Form B to
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`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, the rejection should be withdrawn.
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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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`/ln~enh 1 ,heel/
`Joseph Lucci
`Registration No. 33,307
`
`Stephanie A. Barbosa
`Registration No. 51,430
`
`Date: March 12, 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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`Lupin Ex. 1010 (Page 8 of 8)