TIPO033 USPCT
`USSN 10/514,352
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`CERTIFICATE OF EFS TRANSMISSION
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`I hereby certify that this paper (along with any paper referred to as being attached or enclosed) is being transmitted to the
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`United States Patent and Trademark Otlice on the date shown below via the "Electronic Filing System" in accordance with 37
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`C.F.R. § 1.6(a)(4).
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`Kristin Miele
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`/Kris tin Miele/
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`July 14, 2008
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`Type or print name
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`Signature
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`Date
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`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`Applicants:
`Serial No.:
`Filed:
`For :
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`VERMEERSCH, Hans Wire Pieter et al.
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`10/514,352
`November 12, 2004
`PSEUDOPOLYMORPHIC FORMS OF A HIV PROTEASE INHIBITOR
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`Art Unit: 1625
`Examiner: CHANG, Celia C.
`Confirmation Number: 9009
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`Mail Stop: Patent Application (Response)
`Commissioner for Patents
`P. O. Box 1450
`Alexandria, VA 22313-1450
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`Dear Sir:
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`RESPONSE & AMENDMENT
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`This is a response to the Office communication dated January 14, 2008, response to which is
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`due, with a 3-month extension, on July 14, 2008. Appropriate extension of time request is
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`contained herein.
`[]
`[]
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`Amendments to the Specification begin on page
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`of this paper.
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`Amendments to the claims are reflected in the listing of the claims that begins
`on page 2 of this paper.
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`Amendments to the Drawings begin on page
`an attached replacement sheet.
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`of this paper and include
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`[]
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`Remarks begin on 4 of this paper.
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`EXTENSION OF TIME
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`It is requested that the period for filing a response to the present office action be extended three
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`months to July 14, 2008. The Commissioner is hereby authorized to charge the extension fee of
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`$1,050.00 and any other fees that may be required by this paper to Deposit Account 10-
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`0750/TIP0033 U SPCT/AGK.
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`Page 1 of 7
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`Lupin Ex. 1049 (Page 1 of 7)
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`TIPO033 USPCT
`USSN 10/514,352
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`Listin~ of Claims:
`This" listing of claims replaces all prior versions, and listings, of claims in the captioned
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`application.
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`Claims 1 - 18 (cancelled)
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`19. (New) An ethanolate solvate 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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`hydroxypropylcarb amate.
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`20. (New) A solvate according to claim 19, in which the ratio of compound to ethanol
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`ranges between (5:1) and (1:5).
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`21. (New) A solvate according to claim 19, in which the ratio of compound to ethanol is
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`about 1 : 1.
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`22. (New) A solvate according to claim 21, additionally comprising water molecules.
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`23. (New) A solvate having the formula:
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`°-JU°
`(
`’> ,o,
`,o
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`N ~
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`o. ’k/c..
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`o C2IIsOII
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`~NH2
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`CH3
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`24. (New) A process for preparing an ethanolate solvate according to claim 19
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`comprising the steps of combining (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl
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`( 1 S ,2R)-3 -[ [(4-aminophenyl) sulfonyl] (isobutyl) amino] - 1 -benzyl- 2-
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`hydroxypropylcarbamate with ethanol, and inducing crystallization.
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`25. (New) A process for preparing an ethanolate solvate according to claim 22
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`comprising the steps of combining (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl
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`(1S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-l-benzyl- 2-
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`hydroxypropylcarbamate with ethanol, or mixtures of water and ethanol, and inducing
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`crystallization.
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`26. (New) Pharmaceutical composition comprising a solvate according to claim 19 and a
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`pharmaceutically acceptable carrier or diluent.
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`27. (New) Pharmaceutical composition comprising a solvate according to claim 22 and a
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`pharmaceutically acceptable carrier or diluent.
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`28. (New) A solvate according to claim 23, additionally comprising water molecules.
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`29. (New) The pharmaceutical composition of claim 26, comprising a solid dosage form.
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`Page 2 of 7
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`Lupin Ex. 1049 (Page 2 of 7)
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`TIPO033 USPCT
`USSN 10/514,352
`30. (New) The pharmaceutical composition of claim 26, comprising a solid dosage form.
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`31. (New) The pharmaceutical composition of claim 29, wherein the solid dosage form is
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`a tablet or capsule.
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`32. (New) The pharmaceutical composition of claim 30, wherein the solid dosage form is
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`a tablet or capsule.
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`Page 3 of 7
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`Lupin Ex. 1049 (Page 3 of 7)
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`TIPO033 USPCT
`USSN 10/514,352
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`The claims in the case are 19-32 newly added. These relate to the ethanolate solvate of
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`the compound (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl)
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`sulfonyl] (isobutyl) amino]-l-benzyl-2- hydroxypropylcarbamate. This ethanolate solvate can
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`be partially replaced by water. The newly added claims are supported by the specification.
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`Claim 19 is to the preferred species of Form A. Claims 20 and 21, are directed to the
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`ratio of compound to ethanol, supported by the specification at p. 7, lines 16-37 as well as
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`original claims 9 and 10. Claim 22 is directed to the ethanolate solvate in which some of the
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`ethanol solvent is replaced by water, supported by the specification at p. 7, lines 27-37.
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`Claims 23 and 28 are directed to the preferred species by structure. This claim is
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`supported by the specification, Figure 4, wherein the structure is depicted as a 3-dimensional
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`molecule. Claims 29-32 are directed to solid dosage forms. These claims are supported by
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`the specification at page21.
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`Claims 24 and 25 correspond to original claims Claim 12; and Claims 26 and 27
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`correspond to original Claim 13, respectively.
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`In regard to the restriction requirement and the election as summarized by the
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`Examiner, Applicants have the following comments. The line of distinction drawn between
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`the solvates and the hydrates failed to account for an important aspect of applicants’
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`invention: that is, an ethanolate solvate form in which a portion of the ethanol is replaced by
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`water. This is a different invention from those outlined within the restriction requirement.
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`The mixture of an ethanolate solvate form with a partial replacement by water is not purely a
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`solvatc nor is it purely a hydrate. However, it is primaril~v an ethanolatc solvatc form, and as
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`such should be considered part of a single invention, and examined together in the instant
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`application. The Examiner had assumed the purity of either solvate or hydrate forms, and the
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`response to the restriction requirement operated under the same assumption. Upon review of
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`the invention and revision of the claims to cover the preferred product candidate, Applicants’
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`attorney has come to the realization that the partial replacement of the ethanolate solvate with
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`some water more correctly is part of a single invention, and should correctly be examined
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`together as a seamless part of the elected invention.
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`To the extent that the grounds of rejection apply to the newly added claims, Applicants
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`provide the following comments.
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`Page 4 of 7
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`Lupin Ex. 1049 (Page 4 of 7)
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`TIPO033 USPCT
`USSN 10/514,352
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`Reiection olCClaims 1-I1, 17 under 35 U.S.C. .~ 112, Second Paragraph
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`Claims 1-11 and 17 are rejected under 35 U.S.C. § 112, Second Paragraph, as being indefinite
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`(Office Action at page 2). Specifically, the Office Action states: "It is unclear what is a
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`’pseudomorph’" (Office Action at page 2). Applicant respectfully points out that the term
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`used in the instant application is "pseudopolymorph" and not "pseudomorph".
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`Applicant respectfully disagrees with the Examiner’s assertion that the term
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`"pseudopolymorph" is unclear. However, in the interest of expediting allowance, Applicant
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`has amended the claims at issue to replace the term "pseudopolymorph" with "solvate".
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`Support for the amendment is found in the Specification generally and at page 3. Applicant
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`notes that the "one skilled in the art" cited by the Examiner, Kenneth R. Scddon, a chemistry
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`professor at Queen’s University, Belfast, suggests that the term "solvate" be used in place of
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`the term "pseudopolymorph":
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`So let us be clear. The term pseudopolymorph is now
`commonly being applied to mean the solvate, or (in the specific
`case of water) hydrate, of a material. We gain no new
`understanding by introducing the term "pseudopolymorphs",
`and indeed it is pedagogically misleading. It has been
`introduced into the literature, but I believe it should be
`expunged; editors should insist that it is removed from
`manuscripts in which it is used prior to publication. The term
`"solvate" has been around for centuries, is universally
`understood, and is a perfect descriptor for these materials. Why
`introduce unnecessary and misleading jargon?
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`(Crystal Growth & Design, 4 (6), 1087 1087, 2004).
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`Accordingly, Applicant requests withdrawal of the rejection, insofar as it could apply to the
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`newly added claims in the application, under 35 U.S.C. § 112, Second Paragraph.
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`Reiection of Claims 1-I1~ 16-17 and 12 under 35 U.S.C. ,~ 112, First Paragraph
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`Claims 1-11, 16-17 and 12 are rejected under 35 U.S.C. § 112, First Paragraph, as failing to
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`comply with the enablement requirement (Office Action at pages 3-6). This rejection is
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`moot, as the claims presently in the application relate to the ethanolate solvate form of the
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`compound (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1S,2R)-3-[[(4-aminophenyl)
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`sulfonyl] (isobutyl) amino]-l-benzyl-2-hydroxypropylcarbamate, clearly enabled within the
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`Page 5 of 7
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`Lupin Ex. 1049 (Page 5 of 7)
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`teaching of the application. Accordingly, this rejection should be reconsidered and
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`withdrawn.
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`Reiection oleClaims 1-4, 6-13, and 15-17 under 35 U.S.C. .~ 112, Second Paragraph
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`This rejection is moot, as the claim language objected to does not appear in the newly
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`added claims. Reconsideration and withdrawl of this rejection is respectfully requested.
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`TIPO033 USPCT
`USSN 10/514,352
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`Reieetion oleClaims I3 and 15 under 35 U.S.C. ~ 112, FirstParagraph
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`This rejection is moot, as the claim language objected to does not appear in the newly
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`added claims. Reconsideration and withdrawl of this rejection is respectfully requested.
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`Reieetion ot~Claims I-I3 and 15-17 under 35 U.S.C..~ 102(b), or alternativelF, under 35
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`U.S.C. .~ 103, as being unpatentable over W099/6 7417
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`The Examiner contends that the claims such as the newly added claim 19, are prima
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`facie lack novelty, or, in the alternative are obvious over the cited reference WO 99/67417
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`rejection. Reconsideration of the rejection is respectfully requested, as the reference does not
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`teach or suggest the ethanolate solvate of the specific compound. The Examiner has based the
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`rejection on the fact that the reference does disclose the compound (3R,3aS,6aR)-
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`hexahydrofuro [2,3-b] furan-3 -yl ( 1 S,2R)-3- [[(4-aminophenyl) sulfonyl] (isobutyl) amino] - 1 -
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`benzyl-2-hydroxypropylcarbamate; this is in Figure 5a. However, the Examiner quite
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`inappropriately, combines the disclosure of the compound with vague teachings in the
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`reference. For instance, the Examiner has singled out the phrase "inhibitors wcrc prepared as
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`stock solutions", p. 75, lines 6-9, as well as the alternate carriers at pp 52-57. The rejection
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`confuses a solution of an inhibitor with the actual invention claimed in the instant application,
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`which is to a particular solvate that is a ct3rstalline solid of significant purity, see the teaching
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`in the application, especially at Table I, wherein the "crystal data" of the Form A, the 1:1
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`ethanol solvate form claimed in Claim 19, is detailed, p.8, line 20 and continuing through p.
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`14, line 29. These is significant teaching defining the ethanolate solvate 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]-1-benzyl-2-hydroxypropylcarbamate. This cannot be anticipated or
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`suggested by the brief offhanded "boilcrplatc" found in the reference. Nowhere could the
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`crystalline solvate claimed in Applicants’ invention be suggested, let alone anticipated by this
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`reference.
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`Page 6 of 7
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`Lupin Ex. 1049 (Page 6 of 7)
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`Reconsideration and withdrawal of the rejection is respectfully requested.
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`All the newly added claims are patentable, and notice of allowance of claims 19-32 is
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`respectfully requested.
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`TIPO033 USPCT
`USSN 10/514,352
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`CONCLUSION
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`No additional fee is believed due. The Commissioner is hereby authorized to charge any
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`deficiency or credit any overpayment to Deposit Account No. 10-0750/TIP0033 USPCT/AGK.
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`Johnson & Johnson
`One Johnson & Johnson Plaza
`New Brunswick, NJ 08933-7003
`Phone: (732) 524-1495
`Dated: July 14, 2008
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`Respectfully submitted,
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`/Alana G. Kriegsman!
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`By:
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`Alana Kriegsman, Reg. 41,747
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`Page 7 of 7
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`Lupin Ex. 1049 (Page 7 of 7)
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