DOCKET NO.: TIBO-0063
`
`PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`Hans Wim Pieter Vermeersch
`
`Confirmation No.: 4088
`
`Serial No.: 12/536,807
`
`Group Art Unit: 1625
`
`Filing Date: August 6, 2009
`
`Examiner: Celia C. Chang
`
`For: Pseudopolymorphic Forms of a HIV Protease Inhibitor
`
`Mail Stop Appeal-Brief Patents
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Dear Commissioner:
`
`APPELLANT’S BRIEF PURSUANT TO 37 C.F.R. § 41.37
`
`This brief is being filed in support of Appellant’s appeal from the rejections of claims 15-
`
`17, 20, 21, and 23-36 dated May 22, 2012. A Notice of Appeal was filed on September 17,
`
`2012.
`
`1.
`
`REAL PARTY IN INTEREST
`
`The real party in interest is Janssen R&D Ireland (formerly known as Tibotec
`
`Pharmaceuticals Ltd.), to which the inventors have assigned their rights and which is a subsidiary
`
`of Johnson & Johnson.
`
`o
`
`o
`
`RELATED APPEALS AND INTERFERENCES
`
`None.
`
`STATUS OF CLAIMS
`
`Rejected: 15-17, 20, 21, and 23-36
`
`Allowed: None
`
`Lupin Ex. 1015 (Page 1 of 12)
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`

`

`DOCKET NO.: TIBO-0063
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`- 2 -
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`PATENT
`
`Withdrawn: None
`
`Objected to: None
`
`Cancelled: 1-14, 18, 19, 22
`
`Appealed: 15-17, 20, 21, and 23-36
`
`4.
`
`STATUS OF AMENDMENTS
`
`The amendments made in the March 12, 2012, Response to the September 12, 2011,
`
`Non-Final Office Action have been entered. No further amendments have been made.
`
`5.
`
`SUMMARY OF CLAIMED SUBJECT MATTER
`
`The present invention is directed to hydrated, polymorphic forms of the compound
`
`(3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl)sulfonyl]
`
`(isobutyl) amino]-l-benzyl-2-hydroxypropylcarbamate, as well as compositions comprising those
`
`forms.
`
`The following summary is for the purpose of complying with the provisions of 37 C.F.R.
`
`§ 41.37(c)(1)(v). The entire disclosure should be reviewed to obtain a complete understanding of
`
`the claim language.
`
`Claim Language
`
`Citation to Specification
`
`15. A hydrate of the compound (3R,3aS,6aR)-
`
`Page 6, lines 5-7;
`
`hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-
`
`Page 6, lines 16-18;
`
`aminophenyl) sulfonyl] (isobutyl) amino]-l-benzyl-2-
`
`Page 7, lines 10-11.
`
`hydroxypropylcarbamate in which the ratio of the
`
`compound to water is about 1:0.5 to about 1:3.
`
`16. A hydrate having the formula:
`
`O O
`
`~ NH2
`
`Page 6, lines 5-7;
`
`Page 6, lines 16-18;
`
`Page 7, lines 10-11;
`
`Page 25, line 1 et seq.
`
`H
`
`¯ H20
`
`Lupin Ex. 1015 (Page 2 of 12)
`
`

`

`DOCKET NO.: TIBO-0063
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`- 3 -
`
`PATENT
`
`Claim Language
`
`Citation to Specification
`
`17. A composition comprising a hydrate of the
`
`Page
`
`6, lines 5-7;
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`compound (3R,3aS,6aR)-hexahydrofuro [2,3-b]
`
`Page
`
`6, lines 16-18;
`
`furan-3-yl (1 S,2R)-3- [ [(4-aminophenyl) sulfonyl]
`
`Page
`
`7, lines 10-11; lines 16-37;
`
`(isobutyl) amino]-l-benzyl-2-
`
`Page
`
`20, lines 8-10;
`
`hydroxypropylcarbamate, in which the ratio of
`
`Page
`
`25, line 1 et seq.
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`compound to water is about 1:0.5 to about 1:3, and an
`
`inert carrier.
`
`23. A composition comprising a hydrate having the
`
`Page 6, lines 16-18;
`
`formula:
`
`Page 7, lines 10-11; lines 16-37;
`
`Page 20, lines 8-10.
`
`O
`
`H
`
`¯ H20
`
`OH
`
`and an inert carrier.
`
`6.
`
`GROUNDS OF REJECTION TO BE REVIEWED ON APPEAL
`
`Claims 15-17, 20, 21, and 23-36 stand rejected under 35 U.S.C. § 112, second paragraph,
`
`as allegedly indefinite. Claims 15-17, 20, 21, and 23-36 stand rejected under 35 U.S.C. § 112,
`
`first paragraph, as allegedly lacking written description and enablement.
`
`7.
`
`ARGUMENT
`
`The Examiner erred by failing to identify any reason why a person skilled in the art
`
`would have found the claims indefinite. The Examiner also erred by failing to identify any
`
`reason why such a person would have questioned Applicants’ possession of the claimed
`
`inventions, or any reason why such a person would have been unable to practice those
`
`inventions. Because the Examiner has failed to establish that the claims do not comply with 35
`
`U.S.C. § 112, the rejections of record must be overturned.
`
`Lupin Ex. 1015 (Page 3 of 12)
`
`

`

`DOCKET NO.: TIBO-0063
`
`- 4 -
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`PATENT
`
`The Examiner Has Not Identified Any Respect In Which Those Skilled In The Art Would
`Have Found The Claims Indefinite
`
`The Examiner erred by failing to identify any aspect of the pending claims that those
`
`skilled in the art would have found indefinite.
`
`"The test for definiteness is whether one skilled in the art would understand the bounds of
`
`the claim when read in light of the specification. If the claims read in light of the specification
`
`reasonably apprise those skilled in the art of the scope of the invention, § 112 [second paragraph]
`
`demands no more." Miles Laboratories, Inc. v. Shandon Inc., 997 F.2d 870, 875 (Fed. Cir.
`
`1993). If a skilled artisan can determine whether a particular chemical compound is or is not
`
`within the scope of a claim, the requirement of § 112, second paragraph has been fulfilled. In re
`
`Miller, 441 F.2d 689, 692 (C.C.P.A. 1971). Even a claim that reads on numerous chemical
`compounds is not rendered indefinite by its breadth, so long as the boundaries of patent
`
`protection sought are clearly set forth. In re Barr, 444 F.2d 588, (595 C.C.P.A. 1971). "The
`
`examiner’s focus during examination of claims for compliance with the requirement for
`
`definiteness of 35 U.S.C. 112, second paragraph is whether the claim meets the threshold
`
`requirements of clarity and precision, not whether more suitable language or modes of
`
`expression are available." In re Swinehart, 439 F.2d 210 (C.C.P.A. 1971); M.P.E.P. § 2173.02
`
`(emphasis added).
`
`The Examiner has not come forward with any credible evidence or reasoning
`
`demonstrating that those skilled in the art would not understand the bounds of the instant claims.
`
`Claim 15 stands rejected under 35 U.S.C. § 112, second paragraph, due to an alleged
`
`inconsistency between the fact it is directed to "[a] hydrate" yet embraces multiple hydrates that
`
`each include the specified proportions of water and recited compound. It is well established that
`
`an applicant may present a patent claim that (as in claim 15) uses the definite article "a" to
`
`embrace each of multiple embodiments of an invention (see, e.g., U.S. Patent No. 7,553,974 and
`
`Baldwin Graphic Sys. v. Siebert, Inc., 512 F.3d 1338, 1342-43 (Fed. Cir. 2008)). The Examiner
`
`also alleges that it is unclear "how many hydrates" are within the scope of claim 15 (May 22,
`
`2012 Final Office Action at page 2), but there is no requirement under the patent laws for a claim
`
`to specify how many embodiments it includes. Accordingly, there is no basis for the Examiner’s
`
`assertions regarding alleged indefiniteness.
`
`Lupin Ex. 1015 (Page 4 of 12)
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`

`

`DOCKET NO.: TIBO-0063
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`- 5 -
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`PATENT
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`There is similarly no basis for the Examiner’s assertion that the term "hydrate" is
`
`indefinite. The instant specification expressly defines "hydrates" as "substances that are formed
`
`by adding water molecules." (Specification at page 6, lines 6-7). This clear definition refutes the
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`Examiner’s assertion that those skilled in the art would have found Applicants’ claim language to
`
`have been "unclear" (May 22, 2012 Final Office Action at page 2).
`
`Claims 16 and 23-25 have been rejected because they allegedly make claim 15
`
`"confusing." (id.), but this rejection also lacks basis. None of claims 16 or 23-25 depend from
`
`claim 15, nor does claim 15 depend from them. The Examiner has failed to identify any legal
`
`basis for rejecting a claim because it renders another, non-interdependent claim "confusing."
`
`Even if one of claims 16 and 23-25 did depend from claim 15, there would be no confusion.
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`Claim 16, for example, specifies that the ratio of compound to water be 1 : 1, which is well within
`
`the range (i.e., 1:0.5 to about 1:3) that is recited in claim 15.
`
`Because the Examiner has not supported her rejections for alleged indefiniteness with
`
`evidence or reasoning, the rejection should be overturned.
`
`The Examiner Has Failed To Identify Any Respect In Which Those Skilled In The Art
`Would Have Questioned Applicants’ Possession Of The Claimed Methods
`
`Although the Examiner contends that claims 15-17, 20, 21, and 23-36 do not comply with
`
`35 U.S.C. § 112, first paragraph, she has failed to come forward with any evidence or reasoning
`
`indicating that those skilled in the art would have questioned Applicants’ possession of the
`
`claimed subject matter.
`
`To determine whether a specification contains adequate written description, the critical
`
`question is not whether it provides a literal description of the claimed subject matter but, rather,
`
`whether review of the specification would convey the claimed subject matter to those having
`
`skill in the art. In re Edwards, 568 F.2d 1349, 1351-1352 (C.C.P.A. 1978). In rejecting a claim
`
`for lack of written description, the examiner carries the burden of providing reasons why a
`
`person skilled in the art at the time the application was filed would not have recognized that the
`
`inventor was in possession of the invention as claimed in view of the disclosure of the
`
`application as filed (see M.P.E.P. §2163.04).
`
`Lupin Ex. 1015 (Page 5 of 12)
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`

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`DOCKET NO.: TIBO-0063
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`- 6 -
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`PATENT
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`Here, the Examiner has failed to make any such showing. The Examiner contends that
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`Applicants were not in possession of "hydrates" at the time of filing because the instant
`
`specification describes compounds that are not only hydrated (by virtue of their inclusion of
`
`water) but also include ethanol. (May 22, 2012 Final Office Action at page 32). However, there
`
`is no basis for the Examiner’s restrictive definition of the term "hydrate." As noted above, for
`
`example, the Specification clearly defines "hydrates," in a non-limiting way, as "substances that
`
`are formed by adding water molecules." The presence, or absence, of ethanol is, per this
`
`definition, irrelevant in determining whether a substance of interest is a "hydrate."
`
`The Examiner also appears to contend that the pending claims lack written description
`
`because they recite a "continuous range" of water molecules per molecule of compound, whereas
`
`hydrates allegedly include discrete ratios of these components (id. at page 3).~ Applicants’ use
`
`of a continuous range, however, does not demonstrate any lack of written description. Indeed,
`
`the Examiner’s assertion that hydrates necessarily include discrete amounts of water is plainly
`
`incorrect. It is well known, for example, that hydrates can exist in a non-stoichiometric form that
`
`does not have an integer ratio of water to host molecule.2 The Examiner thus has failed to
`
`identify any basis for questioning Applicants’ possession of the claimed subject matter.
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`Accordingly, the rejection should be overturned.
`
`The Examiner Has Failed To Establish That Those Skilled In The Art Would Not Be Able
`To Practice The Claimed Methods
`
`The Examiner also has erred by failing to come forward with evidence or reasoning
`
`indicating that those skilled in the art would be unable to practice the claimed inventions, and by
`
`failing to rebut the evidence of record demonstrating that Applicants’ disclosure would have
`
`enabled practice of the claimed inventions.
`
`Applicants note that this basis for rejection does not apply to claims 16 or 23-25, which
`do not recite numerical ranges.
`2 This fact is so well-known that citation is believed unnecessary. However, if any doubt
`exists, the nature of this fact can be readily established by conducting an internet search on terms
`such as "non-stoichiometric hydrate." See, e.g., the article entitled "Non-Stoiciometric
`Hydrates," found at http://www.hydrateweb.org/non-stoichiometric-hydrates (courtesy copy
`attached) ("In the fully hydrated state, non-stoichiometric hydrates may, but not necessarily have
`to, show an integer ratio of water to host molecules.")
`
`Lupin Ex. 1015 (Page 6 of 12)
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`

`

`DOCKET NO.: TIBO-0063
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`- 7 -
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`PATENT
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`Enablement must be evaluated against the claimed subject matter. M.P.E.P. 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. The pending claims are directed to, among other
`
`things, hydrates of the claimed compound. As defined in the specification, "hydrates" are
`
`"substances that are formed by adding water molecules." (Specification at page 6, lines 6-7).
`
`Although the Examiner contends Applicants’ disclosure "does not contain sufficient
`
`information to enable one skilled in the pertinent art for recovery of [specific crystal
`
`preparations]" (May 22, 2012 Final Office Action at page 4), the Examiner has failed to identify
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`any respect in which those skilled in the art would have been unable to prepare compositions
`
`wherein water molecules have been added to the recited compound. The specification sets forth
`
`several examples describing the claimed compound and water. Example 2, for example,
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`describes the preparation of a mixture of Form D (acetonate) and Form B. The resulting crystals
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`were a mixture of the acetonate (Form D) and the hydrate (Form B). Various Form B hydrates
`
`were also formed by subjecting Form A to adsorption!desorption tests, as described at 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
`
`for those skilled in the art to make the claimed hydrates (i. e. substances formed by adding water
`
`molecules to the claimed compound) the rejection for alleged lack of enablement should be
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`withdrawn.
`
`The Examiner contends that the claims are not enabled because some of Applicants’
`
`experimental examples produce hydrates that include ethanol or amorphous material (May 22,
`
`2012 Final Office Action at pages 6-7), but this fact is irrelevant in assessing enablement
`
`because, as noted above, such hydrates are within the scope of Applicants’ claims. Because the
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`Examiner’s arguments are based upon a restrictive definition of "hydrate" that is at odds with the
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`definition that Applicants provide in their specification, such arguments fail to support rejection
`
`of the instant claims for alleged lack of enablement. Applicants request the rejection be
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`overturned.
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`Lupin Ex. 1015 (Page 7 of 12)
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`

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`DOCKET NO.: TIBO-0063
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`8
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`PATENT
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`Conclusion
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`Claims 15-17, 20, 21, and 23-36 are not only definite, but are supported by a
`
`specification that demonstrates Applicants’ possession of the claimed inventions and would
`
`enable the skilled person to make and use those inventions. Accordingly, the rejections under 35
`
`U.S.C. § 112, first and second paragraphs, should be overturned.
`
`/Joseph Lucci/
`Joseph Lucci
`Registration No. 33,307
`
`Date: January 25, 2013
`
`Woodcock Washburn LLP
`Cira Centre
`2929 Arch Street, 12th Floor
`Philadelphia, PA 19104-2891
`Telephone: (215) 568-3100
`Facsimile: (215) 568-3439
`
`Lupin Ex. 1015 (Page 8 of 12)
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`

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`DOCKET NO.: TIBO-0063
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`- 9 -
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`PATENT
`
`8.
`
`CLAIMS APPENDIX
`
`Claims 1- 14 Canceled
`
`15. (Previously Presented) A hydrate of the compound (3R,3aS,6aR)-hexahydrofuro [2,3-b]
`
`furan-3-yl ( 1 S,2R)-3- [ [(4-aminophenyl) sulfonyl] (isobutyl) amino]-l-benzyl-2-
`
`hydroxypropylcarbamate in which the ratio of the compound to water is about 1:0.5 to
`
`about 1:3.
`
`16. (Previously Presented) A hydrate having the formula:
`
`O
`
`~ NH2
`
`17. (Previously Presented) A composition comprising a hydrate of the compound
`
`(3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl)sulfonyl]
`
`(isobutyl) amino]-l-benzyl-2-hydroxypropylcarbamate, in which the ratio of compound to
`
`water is about 1:0.5 to about 1:3, and an inert carrier.
`
`18. (Cancelled)
`
`19. (Cancelled)
`
`20. (Previously Presented) The composition of claim 17 wherein the inert carrier is a
`
`pharmaceutically acceptable carrier.
`
`21. (Previously Presented) The composition of claim 20 wherein the pharmaceutically
`
`acceptable carrier is a solid inert carrier.
`
`22. (Cancelled
`
`23. (Previously Presented) A composition comprising a hydrate having the formula:
`
`Lupin Ex. 1015 (Page 9 of 12)
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`

`

`DOCKET NO.: TIBO-0063
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`- 10 -
`
`PATENT
`
`H
`
`¯ H20
`
`OH
`
`and an inert carrier.
`
`24.
`
`(Previously Presented) The composition of claim 23 wherein the inert carrier is a
`
`pharmaceutically acceptable carrier.
`
`25.
`
`(Previously Presented) The composition of claim 24 wherein the pharmaceutically
`
`acceptable carrier is a solid inert carrier.
`
`26. (Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
`
`water is about 1:1 to about 1:2.
`
`27.
`
`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
`
`water is about 1:0.5.
`
`28.
`
`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
`
`water is about 1:1.
`
`29.
`
`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
`
`water is about 1:2.
`
`30.
`
`(Previously Presented) The hydrate of claim 15 wherein the ratio of the compound to
`
`water is about 1:3.
`
`31.
`
`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
`
`water is about 1:1 to about 1:2.
`
`32.
`
`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
`
`water is about 1:0.5.
`
`33.
`
`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
`
`water is about 1:1.
`
`34.
`
`(Previously Presented) The composition of claim 17 wherein the ratio of the compound to
`
`water is about 1:2.
`
`Lupin Ex. 1015 (Page 10 of 12)
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`

`

`DOCKET NO.: TIBO-0063
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`- 11 -
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`PATENT
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`35. (Previously Presented) The composition of claim 17 wherein the ratio of the compound to
`
`water is about 1:3.
`
`36. (Previously Presented) The composition of claim 17 further comprising amorphous
`
`(3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1 S,2R)-3-[[(4-aminophenyl)sulfonyl]
`
`(isobutyl) amino]-l-b enzyl-2-hydroxypropylcarbamate.
`
`Lupin Ex. 1015 (Page 11 of 12)
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`

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`DOCKET NO.: TIBO-0063
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`- 12 -
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`PATENT
`
`o
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`EVIDENCE APPENDIX
`
`None.
`
`10.
`
`RELATED PROCEEDINGS APPENDIX
`
`None.
`
`Lupin Ex. 1015 (Page 12 of 12)
`
`