`

`Office Action Summary
`
`Application No.
`
`Applicant(s)
`
`10/551,205
`
`Examiner
`
`BODOR ET AL.
`
`Art Unit
`
`1623
`Jonathan S. Lau
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE ;l_ MONTH(S) OR THIRTY (30) DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.
`- Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`1 )IZI Responsive to communication(s) filed on 04 January 2008.
`2a)0 This action is FINAL.
`2b)[8J This action is non-final.
`3)0 Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims
`
`4)[8J Claim(s) 1-35 and 56-98 is/are pending in the application.
`4a) Of the above claim(s) 13-35 and 67-81 is/are withdrawn from consideration.
`5)0 Claim(s) __ is/are allowed.
`6)[8J Claim(s) 1-12.56-66 and 82-98 is/are rejected.
`7)0 Claim(s) __ is/are objected to.
`8)0 Claim(s) __ are subject to restriction and/or election requirement.
`
`Application Papers
`
`9)[8J The specification is objected to by the Examiner.
`10)[8J The drawing(s) filed on 28 September 2005 is/are: a)IZ! accepted or b)O objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`11 )0 The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PT0-152.
`
`Priority under 35 U.S.C. § 119
`
`12)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)O All b)O Some* c)O None of:
`1.0 Certified copies of the priority documents have been received.
`2.0 Certified copies of the priority documents have been received in Application No. __ .
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17 .2(a)).
`*Seethe attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`1) [8J Notice of References Cited (PTO-892)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PTO-948)
`3) [8J Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mail Date See Continuation Sheet.
`
`4) 0 Interview Summary (PTO-413)
`Paper No(s)/Mail Date. __ .
`5) 0 Notice of Informal Patent Application
`6) 0 Other: __ .
`
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 08-06)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20080325
`
`417
`
`

`

`Continuation Sheet (PTOL-326)
`
`Application No. 10/551,205
`
`Continuation of Attachment(s) 3). Information Disclosure Statement(s) (PTO/SB/08), Paper No(s)/Mail Date :11 pgs /
`14Nov2006, 10Aug2007,8Nov2007,4Jan2008.
`
`2
`
`418
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 2
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`DETAILED ACTION
`
`This application is the national stage entry of PCT/US04/09387, filed 26 Mar
`
`2004; and claims benefit of provisional application 60/458,922, filed 28 Mar 2003; and
`
`claims benefit of provisional application 60/484,756, filed 02 July 2003; and claims
`
`benefit of provisional application 60/541,24 7, filed 04 Feb 2004.
`
`Claims 1-35 and 56-98 are pending in the current application. Claims 13-35 and
`
`67-81, drawn to non-elected inventions, are withdrawn. Claims 1-12, 56-66, and 82-98
`
`are examined on the merits herein.
`
`However, the parent applications provisional application 60/458,922, filed 28 Mar
`
`2003; provisional application 60/484,756, filed 02 July 2003; and provisional application
`
`60/541,247, filed 04 Feb 2004; upon which priority is claimed fail to provide adequate
`
`support under 35 U.S.C. 112 for the instant claims 1-12, 56-66, and 82-98 of this
`
`application since parent applications 60/458,922, filed 28 Mar 2003; and 60/484,756,
`
`filed 02 July 2003 are not seen to disclose the amorphous cladribine-cyclodextrin
`
`complex of in the independent claims 1, 56 and 82. Written description for claims 1-11
`
`and 56-65 may be found in provisional application 60/541,247, filed 04 Feb 2004,
`
`however no support is found for the percent by weight present in the inclusion complex
`
`and the non-inclusion complex of instant claims 12 and 66, the temperature range of
`
`about 40 to about 80 °C of claims 82 and 83, the temperature range of about 45 to
`
`about 50 °C of claim 85, or the temperature range of about -40 to about -80 °C of claim
`
`89. Thus, the filing date of the instant claims 12, 66, 82, 83, 85, 88 and 89 are deemed
`
`to be the filing date of the instant application, 14 Nov 2006. The filing date of instant
`
`419
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 3
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`claims 1-11, 56-65, 84, 86 and 87 are deemed to be the filing date of provisional
`
`application 60/541,247, filed 04 Feb 2004. If applicant disagrees, applicant should
`
`present a detailed analysis as to why the claimed subject matter has clear support in the
`
`earlier priority applications. Applicant is reminded that such priority for the instant
`
`limitations requires written description and enablement under 35 U.S.C. § 112, first
`
`paragraph.
`
`Election/Restrictions
`
`Applicant's election with traverse of the invention of Group I, claims 1-12, 56-66,
`
`and 82-98, in the reply filed on 04 Jan 2008 is acknowledged. The traversal is on the
`
`ground(s) that the amorphous nature of the complex is part of the special technical
`
`feature of the cladribine-cyclodextrin complex in a solid oral dosage form. This is not
`
`found persuasive because Schultz et al. (US Patent 6,194,395, of record) explicitly
`
`discloses a cladribine-cyclodextrin complex in a solid oral dosage form (column 5, lines
`
`50-52). Further, Schultz et al. references the method of making said solid oral dosage
`
`form disclosed in WIPO Publication WO97/18839 (cited in PTO-892), which is drawn to
`
`the embodiment wherein the melt-extruded forms consist essentially of amorphous
`
`material (page 8, lines 14-15). Therefore WIPO Publication WO97/18839 provides
`
`evidence that it was recognized in the prior art that the product disclosed by Schultz et
`
`al. inherently includes amorphous cladribine-cyclodextrin complex in a solid oral dosage
`
`form. While the International Search Report is factually correct in stating that Schultz et
`
`al. is silent about specific ratios of cladribine to cyclodextrin and amorphous forms, a
`
`420
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 4
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`patent need not teach, and preferably omits, what is well known in the art. By
`
`referencing WIPO Publication WO97/18839 Schultz et al. demonstrates that the
`
`amorphous cladribine-cyclodextrin complex produced by the melt-extrusion method is
`
`well known in the prior art. Finally, to address the scientific issue regarding the
`
`equilibrium presence of both the inclusion and non-inclusion complex, while the
`
`mathematical equation for the equilibrium of the cladribine-cyclodextrin inclusion
`
`complex and the cladribine-cyclodextrin non-inclusion complex would be different for
`
`cladribine and cyclodextrin in a solvent versus cladribine and cyclodextrin in a molten
`
`state, ie. a liquid mixture absent solvent, the equilibrium and thus equilibrium products
`
`would still be present.
`
`The requirement is still deemed proper and is therefore made FINAL.
`
`Claims 13-35 and 67-81 are withdrawn from further consideration pursuant to 37
`
`CFR 1.142(b ), as being drawn to a non elected inventions, there being no allowable
`
`generic or linking claim. Applicant timely traversed the restriction requirement in the
`
`reply filed on 04 Jan 2008.
`
`Specification
`
`The disclosure is objected to because of the following informalities:
`
`a) The blanks identifying the provisional patent application numbers on
`
`page 23, lines 25 and 27 must be replaced with the application numbers.
`
`b) The minor typographical error "com pies" on page 22, line 12.
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`421
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Appropriate correction is required.
`
`Page 5
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`Claim Rejections - 35 USC § 112
`
`The following is a quotation of the second paragraph of 35 U.S.C. 112:
`
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
`
`Claims 2, 11 and 57 are rejected under 35 U.S.C. 112, second paragraph, as
`
`being indefinite for failing to particularly point out and distinctly claim the subject matter
`
`which applicant regards as the invention.
`
`The term "saturated" in claims 2, 11 and 57 is a relative term which renders the
`
`claim indefinite. The term "saturated" is not defined by the claim, the specification does
`
`not provide a standard for ascertaining the requisite degree, and one of ordinary skill in
`
`the art would not be reasonably apprised of the scope of the invention. The following
`
`definition for "saturated" is provided in the specification, page 10 lines 1-13:
`
`The term "saturated" when used in conjunction with a complex of cladribine in amorphous
`cyclodextrin means that the complex is saturated with cladribine, that is, the complex contains the
`maximum amount of cladribine which can be complexed (by means of both inclusion and non(cid:173)
`inclusion complexes) with a given amount of cyclodextrin under the conditions of complexation used.
`A phase solubility study can be used to provide this information, as described in more detail
`hereinafter. (Conditions for the complexation are also described in more detail below.) Alternatively, a
`saturated complex may be arrived at empirically by simply adding cladribine to an aqueous solution of
`the selected cyclodextrin until no more cladribine goes into solution; ultimately, excess cladribine, if
`any, is removed (by filtration or centrifugation) and the solution lyophilized to provide the dry
`saturated complex.
`
`The saturated complex is defined in relation to a maximum amount of cladribine which
`
`can be complexed under the conditions of complexation used. However, this amount is
`
`defined only empirically. A saturated aqueous solution is invoked with regard to this
`
`empirically defined maximum amount of cladribine which can be complexed, but the
`
`422
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
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`Page 6
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`claims are drawn to a saturated complex in a solid oral dosage form, not a saturated
`
`solution. Therefore one of ordinary skill in the art would not be reasonably apprised of
`
`the scope of the invention because the maximum amount would have to be determined
`
`empirically for each composition. For the purpose of furthering prosecution, Examiner
`
`has interpreted the "maximum amount of cladribine which can be complexed" to be the
`
`weight ratio of 1:10 for the cladribine:cyclodextrin complex, based on guidance given on
`
`page 31, lines 18-20.
`
`Claim 2 recites the limitation "the complex" in line 2. There is insufficient
`
`antecedent basis for this limitation in the claim. It is unclear which complex is referred
`
`to by the term "the complex," the inclusion complex (a), the non-inclusion complex (b),
`
`both complexes or the complex cladribin-cyclodextrin complex.
`
`Similarly, claim 11 recites the limitation "saturated complexes" in line 3. There is
`
`insufficient antecedent basis for this limitation in the claim. It is unclear which complex
`
`is referred to by the term "complexes," the inclusion complex (a), the non-inclusion
`
`complex (b), both complexes or the complex cladribin-cyclodextrin complex.
`
`The term "a point located on a phase solubility diagram for saturated complexes
`
`of cladribine in varying concentrations of the cyclodextrin" in claim 11 is a relative term
`
`which renders the claim indefinite. The term "a point located on a phase solubility
`
`diagram for saturated complexes of cladribine in varying concentrations of the
`
`cyclodextrin" is not defined by the claim, the specification does not provide a standard
`
`for ascertaining the requisite degree, and one of ordinary skill in the art would not be
`
`reasonably apprised of the scope of the invention. The broadness of the term "a point
`
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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 7
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`located on a phase solubility diagram" does not necessarily render the term indefinite.
`
`However, no standard is given for what "phase solubility diagram for saturated
`
`complexes of cladribine in varying concentrations of the cyclodextrin" is referred to in
`
`the claim, such as what temperature, pressure, or solvent this phase solubility diagram
`
`describes. Therefore one of ordinary skill in the art would not be reasonably apprised of
`
`the scope of the invention from the term "a point located on a phase solubility diagram
`
`for saturated complexes of cladribine in varying concentrations of the cyclodextrin".
`
`Claim Rejections - 35 USC§ 102
`
`The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that
`
`form the basis for the rejections under this section made in this Office action:
`
`A person shall be entitled to a patent unless -
`
`(b) the invention was patented or described in a printed publication in this or a foreign country or in public
`use or on sale in this country, more than one year prior to the date of application for patent in the United
`States.
`
`Claims 1-5, 11, 56-60, 82-90 and 94-98 are rejected under 35 U .S.C. 102(b) as
`
`being anticipated by Schultz et al. (US Patent 6,194,395, published 27 Feb 2001, of
`
`record) as evidenced by Baert et al. (WIPO Publication WO97/18839, published 29 May
`
`1997, cited in PTO-892).
`
`Schultz et al. discloses a solid pharmaceutical oral dosage form of cladribine
`
`comprising cladribine and cyclodextrin (column 2, lines 31-39), meeting the limitations of
`
`instant claims 1 and 56. The disclosed product is substantially identical to a product-by(cid:173)
`
`process meeting the limitations of instant claims 82-90 and 94-96. Schultz et al.
`
`discloses the use of~- and y-cyclodextrins (column 2, lines 56-58) and derivatives
`
`424
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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 8
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`wherein one or more cyclodextrin hydroxy groups are replaced with groups such as
`
`methyl, hydroxypropyl, carboxymethyl (column 3, lines 26-27) or sulfobutylcyclodextrins
`
`(column 4, lines 22-24 ), meeting the limitations of instant claims 3-5 and 58-60. The
`
`phrase "one or more cyclodextrin hydroxy groups" combined with the absence of
`
`specific structural details of which hydroxyl group is substituted with a methyl group
`
`meets the limitation of "randomly methylated ~-cyclodextrins" of instant claims 3 and 58.
`
`Schultz et al. discloses the solid oral dosage form in the form of a tablet (column 5, lines
`
`37-38) including the excipients sorbitol and magnesium stearate (column 6, lines 2-7),
`
`disclosing a product that is substantially identical to a product-by-process meeting the
`
`limitations of instant claims 97 and 98. Schultz et al. discloses an oral dosage form
`
`comprising up to 15 mg cladribine and cyclodextrin from 100 to 500 mg, which would
`
`lead one of skill in the art to instantly envision a cladribine to cyclodextrin ratio ranging
`
`from 15 mg:100 mg to 15mg:500 mg, or 1 :6.67 to 1 :33.3 by weight (column 6, lines 23-
`
`31 ). These values molar ratios that correspond to "a point located on a phase solubility
`
`diagram for saturated complexes of cladribine in varying concentrations of the
`
`cyclodextrin," meeting the limitations of instant claim 11. The language of instant claim
`
`11 as disclosed requires only that the point be located on a phase solubility diagram for
`
`said complexes, not that the point be located on the curve defining a saturated complex
`
`such as the curve disclosed in the Figure, meaning that any composition according to
`
`claim 1 necessarily meets the limitations of instant claim 11 as disclosed. The instant
`
`specification suggests that maximum amount of cladribine which can be complexed
`
`gives a weight ratio of 1:10 for the cladribine:cyclodextrin complex. Therefore a
`
`425
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 9
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`composition comprising the cladribine:cyclodextrin complex that contains a cladribine to
`
`cyclodextrin ratio of 1 :6.67 describes a composition that comprises a "saturated"
`
`complex and meets the limitations of instant claims 2 and 57. The open language of
`
`"comprising" allows for the presence of uncomplexed cladribine in the composition.
`
`Schultz et al. incorporates-by-reference the method of making said solid oral
`
`dosage form (Schultz et al.column 5, lines 50-52) disclosed in WIPO Publication
`
`WO97/18839, Baert et al., which provides evidence in the embodiment wherein the
`
`melt-extruded forms consist essentially of amorphous material (Baert et al. page 8, lines
`
`14-15). Therefore Baert et al. provides evidence that it was recognized in the prior art
`
`that the product disclosed by Schultz et al. inherently includes amorphous cladribine(cid:173)
`
`cyclodextrin complex in a solid oral dosage form.
`
`To address the scientific issue regarding the equilibrium presence of both the
`
`inclusion and non-inclusion complex, while the equation for the equilibrium of the
`
`cladribine-cyclodextrin inclusion complex and the cladribine-cyclodextrin non-inclusion
`
`complex would be different for cladribine and cyclodextrin in a solvent versus cladribine
`
`and cyclodextrin in a molten state due to the lack of a solvent, the equilibrium and thus
`
`equilibrium products, the cladribine-cyclodextrin inclusion complex and the cladribine(cid:173)
`
`cyclodextrin non-inclusion complex, would still be inherent in the product disclosed by
`
`Schultz et al.
`
`Claims 82-90 and 94-98 are drawn to a product-by-process. The disclosed
`
`product is substantially identical to the instantly claimed product-by-process, an
`
`amorphous solid pharmaceutical oral dosage form comprising cladribine and
`
`426
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 10
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`cyclodextrin. "[E]ven though product-by-process claims are limited by and defined by
`
`the process, determination of patentability is based on the product itself. The
`
`patentability of a product does not depend on its method of production. If the product in
`
`the product-by-process claim is the same as or obvious from a product of the prior art,
`
`the claim is unpatentable even though the prior product was made by a different
`
`process."
`
`In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
`
`(citations omitted) (Claim was directed to a novolac color developer. The process of
`
`making the developer was allowed. The difference between the inventive process and
`
`the prior art was the addition of metal oxide and carboxylic acid as separate ingredients
`
`instead of adding the more expensive pre-reacted metal carboxylate. The product-by(cid:173)
`
`process claim was rejected because the end product, in both the prior art and the
`
`allowed process, ends up containing metal carboxylate. The fact that the metal
`
`carboxylate is not directly added, but is instead produced in-situ does not change the
`
`end product.). See MPEP 2113.
`
`Claim Rejections - 35 USC§ 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
`
`obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set
`forth in section 102 of this title, if the differences between the subject matter sought to be patented and
`the prior art are such that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said subject matter pertains.
`Patentability shall not be negatived by the manner in which the invention was made.
`
`This application currently names joint inventors. In considering patentability of
`
`the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of
`
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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 11
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`the various claims was commonly owned at the time any inventions covered therein
`
`were made absent any evidence to the contrary. Applicant is advised of the obligation
`
`under 37 CFR 1 .56 to point out the inventor and invention dates of each claim that was
`
`not commonly owned at the time a later invention was made in order for the examiner to
`
`consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g)
`
`prior art under 35 U.S.C. 103(a).
`
`Claims 1, 6-10, 12, 56, 61-66, 82 and 91-93 are rejected under 35 U.S.C. 103(a)
`
`as being unpatentable over Schultz et al. (US Patent 6,194,395, published 27 Feb 2001,
`
`of record) in view of Baert et al. (WIPO Publication WO97/18839, published 29 May
`
`1997, cited in PTO-892).
`
`Schultz et al. as evidenced by Baert et al. discloses as above. Schultz et al.
`
`implicitly discloses an oral dosage form comprising up to 15 mg cladribine and
`
`cyclodextrin from 100 to 500 mg, or a cladribine to cyclodextrin ratio ranging from 1 :6.67
`
`to 1 :33.3 by weight (column 6, lines 23-31 ).
`
`Schultz et al. does not specifically disclose the composition comprising a
`
`cladribine to cyclodextrin ratio from about 1:10 to about 1 :16 (instant claims 6, 7, 10, 61,
`
`62 and 65), or a ratio of about 1 :14 (instant claims 8 and 63) or about 1 :11 (instant
`
`claims 9 and 64). Schultz et al. does not specifically disclose the complex wherein from
`
`about 30 to about 40 percent by weight of the cladribine is in the inclusion complex (a)
`
`and from about 70 to about 60 percent by weight of the cladribine is in the non-inclusion
`
`complex (b) (instant claims 12 and 66). Schultz et al. does not specifically disclose the
`
`product-by-process wherein 12.00 parts by weight of cladribine and 172.50 parts by
`
`428
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`Application/Control Number: 10/551,205
`Art Unit: 1623
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`Page 12
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`weight of hydroxypropyl-~-cyclodextrin are introduced in step (i) of the process (instant
`
`claim 91 and 93), to give a cladribine to cyclodextrin ratio of 1 :14.38.
`
`Schultz et al. does not specifically disclose the product-by-process wherein 16.35
`
`parts by weight of cladribine and 172.50 parts by weight of the hydroxypropyl-~(cid:173)
`
`cyclodextrin are introduced in step (i) of the process (instant claim 92), to give a
`
`cladribine to cyclodextrin ratio of 1:10.55.
`
`Baert et al. discloses a solid mixture comprising one or more cyclodextrins and
`
`an insoluble active ingredient embedded into the cyclodextrin carrier (abstract), and
`
`teaches ratios of active ingredient to cyclodextrin of from about 1:100 to 100:1, from
`
`about 1 :5 and 5:1 and from about 1 :3 to 3:1 (page 11, lines 1-5). These ratios are
`
`interpreted as mole ratios because Baert et al. teaches the use of different active
`
`ingredients with different molecular weights. A mole ratio of active ingredient to
`
`cyclodextrin of about 1 :3 for cladribine (MW 285.7 g/mol) and ~-cyclodextrin (MW 1135
`
`g/mol) gives a ratio by weight of approximately 1 :11.9. The ratio of 1 :11.9 meets the
`
`I imitation of both a ratio of about 1 : 11 and a ratio of about 1 : 14 according to the non-
`
`I im iting definition of "about" as a variance of 20% provided in the instant specification
`
`page 9, lines 6-11.
`
`It would have been obvious to one of ordinary skill in the art at the time of the
`
`invention to practice the solid pharmaceutical oral dosage form of cladribine comprising
`
`cladribine and cyclodextrin disclosed by Schultz et al. in the ratios of cladribine and
`
`cyclodextrin taught by Baert et al. One of ordinary skill in the art would be motivated to
`
`combine the Schultz et al. and Baert et al. because Schultz et al. incorporates-by-
`
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`Application/Control Number: 10/551,205
`Art Unit: 1623
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`Page 13
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`reference Baert et al. and because Baert et al. suggests that improving a similar product
`
`according to the teachings of Baert et al. has beneficial properties such as high
`
`bioavailability and dissolution rate (Baert et al. page 7, lines 25-27). One of ordinary
`
`skill in the art would have an expectation of success because the ratios taught by Baert
`
`et al. fall within the range of ratios that is implicitly disclosed by Schultz et al. Schultz et
`
`al. in view of Baert et al. does not teach the specific cladribine to cyclodextrin ratios of
`
`1 :14.38 or 1 :10.55, however these ratios are encompassed by the prior art and Baert et
`
`al. suggests optimization of the ratio (Baert et al. page 11, lines 1-5). See also MPEP
`
`2144.05 II.A, "Generally, differences in concentration or temperature will not support the
`
`patentability of subject matter encompassed by the prior art unless there is evidence
`
`indicating such concentration or temperature is critical." Schultz et al. in view of Baert et
`
`al. does not specifically disclose the complex wherein from about 30 to about 40 percent
`
`by weight of the cladribine is in the inclusion complex (a) and from about 70 to about 60
`
`percent by weight of the cladribine is in the non-inclusion complex (b ). However, it is
`
`well known in the art that the formation of an inclusion complex from a non-inclusion
`
`complex is an equilibrium process, and the position of this equilibrium is dependent on
`
`the concentrations of the cladribine and cyclodextrin. This molecular inclusion
`
`equilibrium is a process inherent in the formation of the inclusion complex in both
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`aqueous solutions and hot melt liquid mixtures, and Baert et al. teaches variation of the
`
`ratio of cladribine to cyclodextrin and hence their relative concentration.
`
`It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594)
`
`discuss the support of rejections wherein the prior art discloses subject matter which
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`430
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`

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`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 14
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`there is reason to believe inherently includes functions that are newly cited or is
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`identical to a product instantly claimed, namely the position of the equilibrium process
`
`governing formation of an inclusion complex and a non-inclusion complex. In such a
`
`situation the burden is shifted to the applicants to "prove that subject matter shown to be
`
`in the prior art does not possess characteristic relied on" (205 USPQ 594, second
`
`column, first full paragraph).
`
`Conclusion
`
`No claim is found to be allowable.
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Jonathan S. Lau whose telephone number is 571-270-
`
`3531. The examiner can normally be reached on Monday - Thursday, 9 am - 4 pm
`
`EST.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
`
`supervisor, Shaojia Anna Jiang can be reached on 571-272-0627. The fax phone
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`number for the organization where this application or proceeding is assigned is 571-
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`273-8300.
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`431
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`

`

`Application/Control Number: 10/551,205
`Art Unit: 1623
`
`Page 15
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`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
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`published applications may be obtained from either Private PAIR or Public PAIR.
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`Status information for unpublished applications is available through Private PAIR only.
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`For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
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`
`Jonathan Lau
`Patent Examiner
`Art Unit 1623
`
`/Shaojia Anna Jiang, Ph.D./
`Supervisory Patent Examiner, Art Unit 1623
`
`432
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`

`

`Notice of References Cited
`
`Application/Control No.
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`10/551,205
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`Examiner
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`Jonathan S. Lau
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`U.S. PATENT DOCUMENTS
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`Applicant(s)/Patent Under
`Reexamination
`BODOR ET AL.
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`Art Unit
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`1623
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`U.S. Patent and Trademark Office
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`Notice of References Cited
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`Part of Paper No. 20080325
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`433
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`

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`FOR THE PURPOSES OF INFORMATION ONLY
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`Codes used to identify States party to the PCT on the front pages of pamphlets publishing international
`applications under the PCT.
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`435
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`

`

`WO 97/18839
`
`PCT/EP96/05118
`
`-1-
`SOLID MIXTURES OF CYCLODEXTRINS PREPARED VIA MELT-EXTRUSION
`
`5
`
`The present invention involves a process for preparing solid mixtures by melt-extrusion
`comprising one or more active ingredients, preferably one or more practically insoluble
`active ingredients and one or more cyclodextrins. The invention further concerns
`pharmaceutical compositions comprising the above mixture.
`
`10 WO 94/ 1103 l, published on May 5, 1994, discloses a method of manufacturing a high(cid:173)
`quality enclosure compound using extrusion techniques. In this document the
`extrusion of cyclodextrins together with an active ingredient is mentioned. However,
`the document discloses the use of a wet mixture (i.e. including water or another
`solvent) to feed into the extruder.
`
`15
`
`20
`
`25
`
`30
`
`35
`
`French patent application 2,705,677 published on December 2, 1994 describes micro(cid:173)
`granules obtained by extrusion-spheronisation containing a cyclodextrin. The
`extrusion-spheronisation technique is the combination of an agglomeration technique,
`i.e. extrusion, and a shaping technique, i.e. the spheronisation. Said patent application
`actually teaches the formation of microgranulates containing 13-cyclodextrin
`(Kleptose®) and microcrystalline cellulose (A vicel®) and as active ingredients
`ketoprofen and paracetamol. The extrusion technique used in the above-mentioned
`patent application consists in preforming a humid mass by forcing said human mass
`through a nozzle thus forming long strands of extruded material. The document does
`not mention melt-extrusion at all.
`
`EP 0,665.009, published as