`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTNIENT 0F COMIVIERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PA'i'EN'i'S
`PO BOX I450
`A1exand1'ia1 Virginia 22313- 1450
`WWW uspto gov
`
`11/399,879
`
`04/06/2006
`
`Gregory T. W’ent
`
`34550-705501
`
`3491
`
`.
`EXAMINER
`.
`.
`.
`.
`Wllson Sons1n1 Goodrlch & Rosatl —
`W1 —
`”9°
`945“
`Adamas Pharmaceuticals, Inc.
`CARTER, KENDRA D
`
`650 Page Mill Road
`pale Alto, CA 94304
`
`ART LNIT
`—1627
`
`PAPER NUMBER
`
`MAIL DATE
`
`02/08/201 1
`
`DELIVERY MODE
`
`PAPER
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`PTOL790A (Rev 04/07)
`
`IPR2015—00410
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`Petitioners' EX. 1022
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`Page 1
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`IPR2015-00410
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`

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`
`Application No.
`Applicant(s)
`
`11/399,879
`
`WENT ET AL.
`
`Office Action Summary
`
`Examiner
`KENDRA D. CARTER
`
`Art Uni,
`1627
`
`
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period tor Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g MONTH(S) OR THIRTY (30) DAYS,
`
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF T-IIS COMMUNICATION.
`Extensions of tIme may be available under the provisions of 37 CFR1. 136(a).
`In no event, however, may a reply be timely filed
`after SIX() MONTHS from the mailing date of this communication
`It 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 apoiication to become ABANDONED (35 U.S.C. § 133).
`Any repIy received by the Office later than three months af‘terthe mailing date of this communication, even iftimely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`
`
`Status
`
`DIE Responsive to communication(s) filed on 05 November 2010.
`
`2a)I:I This action is FINAL.
`
`2b)lZ This action is non—final.
`
`3)|:| 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 Exparte Quay/e, 1935 CD. 11, 453 DC. 213.
`
`Disposition of Claims
`
`4)IZ Claim(s) 12 23 24 28 29 50 51 53 55-60 62 66 67 69-72 and 74-85 is/are pending in the application.
`4a) Of the above claim(s)
`is/are withdrawn from consideration.
`5 El Claim 3)
`is/are allowed.
`
`12 23 24 28 29 50 51 53 55-60 62 66 67 69- 72 and 74-85 is/are rejected.
`
`is/are objected to.
`
`are subject to restriction and/or election requirement.
`
`Application Papers
`
`9)|:I The specification is objected to by the Examiner.
`
`OH] The drawing(s) filed on _ is/are: a)|:l accepted or b)I:I 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)|:I The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.
`
`Priority under 35 U.S.C. § 119
`
`12)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`
`a)I:I All
`
`b)I:| Some * c)|:| None of:
`
`1.I:I Certified copies of the priority documents have been received.
`
`2.|:| Certified copies of the priority documents have been received in Application No. _
`
`3.|:I 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)).
`
`* See the attached detailed Office action for a list of the certified copies not received.
`
` Attachment(s)
`
`
`
`Notice of References Cited (PTO-892)
`1)
`2) I: Notice of Draftsperson’s Patent Drawing Review (PTO-948)
`3) IXI Information Disclosure Statement(s) (PTO/SB/08)
`Paper No(s)/Mai| Date 10/01/10,'11/5/10.
`U 8 Patent and Trademark Office
`PTOL-326 (Rev. 08-06)
`
`4) D Interview Summary (PTO-413)
`Paper N0(5 )/Mai| Date.
`5)I:I Notice of Informal Paton—IApplication
`6)I:| Other:—
`
`Ottice Action Summary
`
`Part of Paper No./Mai| Date 20110203
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`IPR2015—00410
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`Application/Control Number: 11/399,879
`Art Unit: 1627
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`Page 2
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`DETAILED ACTION
`
`Claims 12, 23, 24, 28, 29, 50, 51, 53, 55—60, 62, 66, 67, 69-72 and 74-85 are
`
`pending. Claims 23, 24, 50, 51, 71 and 72 are amended, and claims 74-85 are new.
`
`Claims 1-11, 13-22, 25-27, 30-49, 52, 54, 61, 63-65, 68 and 73 are cancelled. All
`
`pending claims are drawn to the elected species memantine (species of NMDAr
`
`antagonist), donepezil (species of AChel), and dementia of the Alzheimer’s type
`
`(species of condition) in the reply filed on February 18, 2010.
`
`In light of further consideration and applicant’s arguments being persuasive to
`
`overcome the 35 U.S.C. 102(e) rejection, the NEW NON-FINAL rejections are below.
`
`Particularly, Moebius does not specifically teach memantine in an extended release
`
`formulation especially compared to the arguments over the properties of the extended
`
`release formulation. The previously made 35 U.S.C. 102(e) and 103(a) rejection are
`
`withdrawn. The Double Patenting rejections are upheld because the claims were not
`
`found allowable and a terminal disclaimer has not been provided.
`
`The Went Declaration is discussed below. Applicant's arguments with respect to
`
`the 35 U.S.C. 102(e) and 103(a) rejection have been considered but are moot in view of
`
`the new ground(s) of rejection.
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`Application/Control Number: 11/399,879
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`Page 3
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`Double Patenting
`
`The nonstatutory double patenting rejection is based on a judicially created
`
`doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the
`
`unjustified or improper timewise extension of the “right to exclude” granted by a patent
`
`and to prevent possible harassment by multiple assignees. A nonstatutory
`
`obviousness—type double patenting rejection is appropriate where the conflicting claims
`
`are not identical, but at least one examined application claim is not patentably distinct
`
`from the reference claim(s) because the examined application claim is either anticipated
`
`by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140
`
`F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29
`
`USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir.
`
`1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422
`
`F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163
`
`USPQ 644 (CCPA 1969).
`
`A timely filed terminal disclaimer in compliance with 37 CFR 1.321 (c) or 1.321(d)
`
`may be used to overcome an actual or provisional rejection based on a nonstatutory
`
`double patenting ground provided the conflicting application or patent either is shown to
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`be commonly owned with this application, or claims an invention made as a result of
`
`activities undertaken within the scope of a joint research agreement.
`
`Effective January 1, 1994, a registered attorney or agent of record may sign a
`
`terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with
`
`37 CFR 3.73(b).
`
`1)
`
`Claims 12, 23-25, 28, 29 and 50 are provisionally rejected on the ground of
`
`nonstatutory double patenting over claims 12-14 and 21-29 of copending
`
`Application No. 12/753,769. This is a provisional double patenting rejection since
`
`the conflicting claims have not yet been patented.
`
`The subject matter claimed in the instant application is fully disclosed in the
`
`referenced copending application and would be covered by any patent granted on that
`
`copending application since the referenced copending application and the instant
`
`application are claiming common subject matter, as follows: an extended formulation of
`
`memantine and donepezil with the same dissolution profile that can be administered
`
`simultaneously in a single composition. The amounts of memantine can range between
`
`10 to 80, 20 to 60, or 40 to 80 mg per dose.
`
`Furthermore, there is no apparent reason why applicant would be prevented from
`
`presenting claims corresponding to those of the instant application in the other
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`Page 5
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`copending application. See In re SchneI/er, 397 F.2d 350, 158 USPQ 210 (CCPA
`
`1968). See also MPEP § 804.
`
`2)
`
`Claims 12, 23-25, 28, 29 and 50 are provisionally rejected on the ground of
`
`nonstatutory double patenting over claims 12-14 and 21-29 of copending
`
`Application No. 12/757,795. This is a provisional double patenting rejection since
`
`the conflicting claims have not yet been patented.
`
`The subject matter claimed in the instant application is fully disclosed in the
`
`referenced copending application and would be covered by any patent granted on that
`
`copending application since the referenced copending application and the instant
`
`application are claiming common subject matter, as follows: an extended formulation of
`
`memantine and donepezil with the same dissolution profile that can be administered
`
`simultaneously in a single composition. The amounts of memantine can range between
`
`10 to 80, 20 to 60, or 40 to 80 mg per dose.
`
`Furthermore, there is no apparent reason why applicant would be prevented from
`
`presenting claims corresponding to those of the instant application in the other
`
`copending application. See In re Schnel/er, 397 F.2d 350, 158 USPQ 210 (CCPA
`
`1968). See also MPEP § 804.
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`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
`
`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(0) and potential 35 U.S.C. 102(e), (f) or (g)
`
`prior art under 35 U.S.C. 103(a).
`
`1)
`
`Claims 12, 23, 24, 28, 29, 50, 51, 60, 62, 66, 67, 69, 70-72, 74, 77, 79, 80, 83
`
`and 85 are rejected under 35 U.S.C. 103(a) as being unpatentable over Moebius
`
`(US 2004/0087658 A1) in view of Ditzler (Arnzneim.—Forsch./Drug Res., 1991, vol.
`
`II, no. 8, pp. 773-780) and Nurnberg et al. (US 5,382,601).
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`Moebius teach a drug combination therapy for the treatment of dementia in
`
`Alzheimer’s comprising memantine or a pharmaceutical salt and donepezil
`
`hydrochloride (see abstract, paragraph 5, lines 1-2; claims 1, 7, 11, 12 and 16;
`
`addresses claims 12, 50 and 62). The formulation can be administered orally in the
`
`form of a capsule or the like in a controlled or postponed release in the form of
`
`erodible/degradable matrices (see paragraphs 192 and 194; addresses claims 12, 50
`
`and 60). The two drugs can be administered in unit formulations as one composition
`
`simultaneously with a therapeutically effective dosage in a ranging of 1-200 mg/day for
`
`each drug (see paragraphs 24 and 192; addresses claims 28, 29, 51, 62, 70 and 72). A
`
`human patient population was administered 10 mg of memantine and 10 mg of
`
`donepezil per day for 6 months (see paragraph 487 and paragraph 492; addresses
`
`claims (12, 50, 53, 65 and 72). Excipient such as hydroxypropyl methyl cellulose and
`
`polyvinylpyrrolidone may be used (see paragraph 193; addresses claims 79 and 85).
`
`Moebius does not specifically teach the following: 1) a hydrochloride salt of
`
`memantine (claim 71 and 72); 2) the specific amounts or ranges of memantine in Claims
`
`12, 23, 24, 50, 51, 71, 72 and 80); 3) memantine in an extended release (claims 12 and
`
`50); and 4) wherein the release of the memantine is biphasic (claims 77 and 83).
`
`Ditzler teaches the efficacy and tolerability of memantine in patients with
`
`dementia syndrome (see title). Adverse drug effects were observed and represent an
`
`excessive pharmacodynamic effect resulting from a too rapid dose increase (see page
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`773, right column, first paragraph). Questions about adverse events and side effects
`
`were asked in accordance with the standerdized DOTES/TWIS method. Table 7 shows
`
`the recorded events for placebo and memantine. The events recorded during the study
`
`on the basis of the standardized DOTES/TWls method on the one hand show for both
`
`treatments a non-specific spectrum of events, and on the other hand the following
`
`known adverse reactions can be attributed to memantine excitation/agitation, increased
`
`motor activity, insomnia, and restlessness (day 14), which however receded in the
`
`course of the treatment, as can be seen from the lower frequency of reports on day 42.
`
`However, the adverse reactions recorded in DOTES/TWIS were not serious and were
`
`transient, and very probably the result of a too rapid dose increase at the beginning of
`
`treatment. The dose should therefor be increased more slowly and adjusted to the
`
`individual situation until the optimal effect has been reached (see page 778, right
`
`column, last paragraph).
`
`Nurnberg et al. teach a two-stage release (i.e. biphasic) profile composition of
`
`memantine (see title and abstract). The dosage provides an extended controlled-
`
`release profile such that the active substance can be conveniently and reliable released
`
`over an extended period in at least two stages (see column 2, lines 40-50).
`
`To one of ordinary skill in the art at the time of the invention would have found it
`
`obvious and motivated to combine the method of Moebius and memantine specifically in
`
`an extended release because Ditzler teach that in the treatment of dementia with
`
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`mementine, the dose should be increased more slowly and adjusted to the individual
`
`situation until the optimal effect has been reached (see page 778, right column, last
`
`paragraph). Particularly, adverse drug effects were observed and represent an
`
`excessive pharmacodynamic effect resulting from a too rapid dose increase (see page
`
`773, right column, first paragraph). Further, at the time of the invention, extended
`
`release compositions of mementine were known. Specifically, Nurnberg et al. teach a
`
`two-stage release (i.e. biphasic) profile composition of memantine (see title and
`
`abstract), wherein the dosage provides an extended controlled-release profile such that
`
`the active substance can be conveniently and reliable released over an extended period
`
`in at least two stages (see column 2, lines 40-50). Thus, one would be motivated to
`
`provide mementine in an extended release form to avoid adverse drug effects and
`
`provide a convenient and reliable release of mementine.
`
`In regards to the properties of the drug combination such as dissolution profiles
`
`and Tmax values in claims 12, 66, 67, 69 and 74, it is considered that these properties
`
`are obvious to the method step of administering memantine and donepezil in an
`
`extended release dosage. Where the claimed and prior art products are identical or
`
`substantially identical in structure or composition, or are produced by identical or
`
`substantially identical processes, a prima facie case or either anticipation or
`
`obviousness has been established. Thus, the claiming of a new use, new function or
`
`unknown property which is inherently present in the prior art does not necessarily make
`
`the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA
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`1977). Further Moebius teach that the rate of memantine absorption following
`
`administration of 10 mg was moderate with peak plasma concentrations achieved at 6.5
`
`hours with or without donepezil (see paragraph 479). A 10 mg administration of
`
`donepezil was moderate with peak plasma concentrations achieved at 3.4 and 3.3
`
`hours without and with memantine respectively (see paragraph 482). Additionally,
`
`Ditzler teaches that the dose should therefor be increased more slowly and ad'usted to
`
`the individual situation until the optimal effect has been reached (see page 778, right
`
`column, last paragraph). Thus, the properties of claims 12, 66, 67, 69 and 74 are
`
`obviously taught.
`
`To one of ordinary skill in the art at the time of the invention would have found it
`
`obvious and motivated to combine the method of Moebius and the hydrochloride salt of
`
`memantine because Moebius teach that pharmaceutical salts of memantine can be
`
`used. Selection of a known material based on its suitability for its intended use is
`
`obvious absent a clear showing of unexpected results attributable to the Applicant’s
`
`specific selection. See e.g., In re Leshin, 227 F.2d 197, 125 USPQ 416 (CCPA 1960).
`
`To one of ordinary skill in the art at the time of the invention would have found it
`
`obvious and motivated to combine the method of Moebius and the specific amounts or
`
`ranges of memantine in claims 12, 23, 24, 50, 51, 71, 72 and 80 because Moebius
`
`teach that memantine and donepezil can be administered in unit formulations as one
`
`composition simultaneously with a therapeutically effective dosage in a ranging of 1-200
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`mg/day for each drug (see paragraphs 24 and 192).
`
`It is the normal desire of scientists
`
`or artisans to improve upon what is already generally known provides the motivation to
`
`determine where in a disclosed set of percentage ranges is the optimum combination of
`
`percentages. See In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980)
`
`(“[D]iscovery of an optimum value of the result effective variable in a known process is
`
`ordinarily within the skill of the art.” See, e.g., In re Baird, 16 F.3d 380, 29 USPQ2d
`
`1550 (Fed. Cir. 1994); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992).
`
`In
`
`re Paterson Appeal No. 02-1189 (Fed. Cir. January 8, 2003).
`
`It is noted that "[W]here
`
`the general conditions of a claim are disclosed in the prior art, it is not inventive to
`
`discover the optimum or workable ranges by routine experimentation." In re Aller, 220
`
`F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.)
`
`To one of ordinary skill in the art at the time of the invention would have found it
`
`obvious and motivated to combine the method of Moebius in view of Ditzler and wherein
`
`the release of the memantine is biphasic because is within the skill of the art to make a
`
`biphasic release such that the active substance can be conveniently and reliable
`
`released over an extended period in at least two stages (see Nurnberg et al.; column 2,
`
`lines 40-50).
`
`2)
`
`Claims 53-59, 75, 76, 81 and 82 are rejected under 35 U.S.C. 103(a) as being
`
`unpatentable over Moebius (US 2004/0087658 A1) in view of Ditzler (Arnzneim.-
`
`Forsch./Drug Res., 1991, vol. II, no. 8, pp. 773-780) as applied to claims 12, 23, 24,
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`28, 29, 50, 51, 60, 62, 66, 67, 69, 70-72, 74, 79, 80 and 85, in further view of Laurin
`
`et al. (US 2006/0079578 A1).
`
`Moebius and Ditzler teachings are as applied above in claims 12, 23, 24, 28, 29,
`
`50, 51, 60,62, 66, 67, 69, 70-72, 74, 79, 80 and 85 above.
`
`Moebius and Ditzler do not specifically teach the formulation in a bead and/or
`
`pellet (claim 55) with an extended release coating (claim 56) comprising ethyl cellulose
`
`and polyvinylpyrrolidone (claims 57-59). Moebius and Ditzler also do not teach the
`
`specific percentages that memantine is in an extended release form and then the
`
`remaining in an immediate release form as specified in claims 75, 76, 81 and 82.
`
`Laurin et al. teach oral therapeutic formulations that can comprise donepezil and
`
`memantine to treat Alzheimer’s disease (see paragraph 363) in the form of a pellet (see
`
`paragraph 381) or as a multi-bead in a controlled (i.e. extended, delayed or slow)
`
`release (see paragraph 384). The formulation can be a combination of immediate,
`
`controlled, sustained, extended or delayed technologies to achieve the desired regimen
`
`(see paragraph 385). The bead can contain the active agent with a coated polymer,
`
`and/or with mix of active agent and polymer or any different order of such layers on the
`
`core, within each case, selected active agent concentrations of components in the layer
`
`(see paragraph 389-391). The capsule can contain multiple types of beads as
`
`described above having different timing of release or different rates of release of active
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`agent (see paragraph 392). Suitable polymers for coating include ethyl cellulose (see
`
`paragraphs 395 and 400) and polyvinylpyrolidone (see paragraph 400).
`
`To one of ordinary skill in the art at the time of the invention would have found it
`
`obvious and motivated to combine the method of Moebius in view of Ditzler and a bead
`
`and/or pellet (claim 55) with an extended release coating (claim 56) comprising ethyl
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`cellulose and polyvinylpyrrolidone (claims 57-59) because Laurin et al. that Alzheimer
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`type formulations can be formulated with the above components to provide different
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`timing release or different rates of release of the active agent (see the teachings of
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`Laurin et al.). Selection of a known material based on its suitability for its intended use is
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`obvious absent a clear showing of unexpected results attributable to the Applicant’s
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`specific selection. See e.g., In re Leshin, 227 F.2d 197, 125 USPQ 416 (CCPA 1960).
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`To one of ordinary skill in the art at the time of the invention would have found it
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`obvious and motivated to combine the method of Moebius in view of Ditzler and wherein
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`80% or 95% of memantine is in an extended release form and the remainder is in an
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`immediate release form because Laurin et al. that Alzheimer type formulations can be
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`formulated with the above components to provide different timing release or different
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`rates of release of the active agent (see the teachings of Laurin et al.). Further Laurin et
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`al. teach that formulations can be a mixture of The formulation can be a combination of
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`immediate, controlled, sustained, extended or delayed technologies to achieve the
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`desired regimen (see paragraph 385). Lastly, Ditzler teach that in the treatment of
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`dementia with mementine, the dose should be increased more slowly and adjusted to
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`the individual situation until the optimal effect has been reached in order to avoid drug
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`effects (see page 778, right column, last paragraph). Thus, one skilled in the art would
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`be able to formulate a composition of claims 75, 76, 81 and 82 in order to avoid drug
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`effects.
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`3)
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`Claims 77 and 83 are rejected under 35 U.S.C. 103(a) as being unpatentable
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`over Moebius (US 2004/0087658 A1) in view of Ditzler (Arnzneim.—Forsch./Drug
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`Res., 1991, vol. II, no. 8, pp. 773-780) as applied to claims 12, 23, 24, 28, 29, 50, 51,
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`60, 62, 66, 67, 69, 70-72, 74, 79, 80 and 85, in further view of Hutchinson (US
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`4,767,628).
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`Moebius and Ditzler teachings are as applied above in claims 12, 23, 24, 28, 29,
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`50,51, 60,62, 66, 67,69, 70-72, 74, 79, 80 and 85 above.
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`Moebius and Ditzler do not specifically teach wherein the release of the
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`memantine is monophasic.
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`Hutchinson teaches continuous release pharmaceutical compositions that are
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`monophasic such that the composition is released continuously over an extended
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`period. The compositions could have significant practical advantages in clinical
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`practices (see abstract and column 1, lines 10-20).
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`To one of ordinary skill in the art at the time of the invention would have found it
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`obvious and motivated to combine the method of Moebius in view of Ditzler and wherein
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`the release of the memantine is monophasic because is within the skill of the art to
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`make a monophasic release in order to potentially provide significant practical
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`advantages in clinical practices (see Hutchinson; abstract and column 1, lines 10-20).
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`W
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`Response to Arguments
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`The Declaration teaches that a person having ordinary skill in the art at the
`time of filing of the Application would have lacked any motivation to
`prepare an extended release for of memantine, as duration of activity is
`not really an issue with memantine. Now would that person be motivated
`with an expectation of success in significantly reducing memantine's CNS
`side effects to the point where it could be administered once per day,
`alone or with donepezil.
`In a pharmacokinetic study subjects given
`immediate release (IR) memantine, extended release memantine in Form
`A, extended release memantine in Form B, and extended release
`memantine in Form C. Forms B and C are formulated according to the
`Applicant’s claims. Forms B and C fall within the initial dC/DT requirement
`specific in the application and the subjects given IR and Form A
`formulations did not. Further, CNS side effects were reduced in Form B
`and C formulations over the IR and Form A formulation. Lastly, in a
`steady state blood plasma study between Form B and the commercially
`available IR form of memantine, the Form B formulation achieved overall
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`higher blood plasma concentrations and memantine exposure than the IR
`formulation. The Cmax was 20% higher than the average Cmax of the IR
`formulation and an AUCg4 that was 15% higher than the average AUCg4 of
`the IR formulation. Additionally, there were no incidences of memantine-
`reIated CNS side effects despite having reached higher plasma
`concentration and AUC.
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`The Examiner has considered the declaration and does not find it persuasive to
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`overcome the new rejections.
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`In particular, one would have found it obvious and
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`motivated to administer memantine in an extended release formulation because of the
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`following teachings: 1) Moebius teach a drug combination therapy for the treatment of
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`dementia in Alzheimer’s comprising memantine or a pharmaceutical salt and donepezil
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`hydrochloride (see abstract, paragraph 5, lines 1-2; and claims 1, 7, 11, 12 and 16); 2)
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`Moebius further teaches the formulation can be administered orally in the form of a
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`capsule or the like in a controlled or postponed release in the form of
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`erodible/degradable matrices (see paragraphs 192 and 194;); 3) Ditzler teach that in
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`the treatment of dementia with mementine, the dose should be increased more slowly
`
`and adjusted to the individual situation until the optimal effect has been reached (see
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`page 778, right column, last paragraph); 4) Particularly Ditzler teaches that the adverse
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`drug effects were observed and represent an excessive pharmacodynamic effect
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`resulting from a too rapid dose increase (see page 773, right column, first paragraph);
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`5) Further, at the time of the invention, extended release compositions of mementine
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`were known according to Nurnberg et al., in which teach a two-stage release (i.e.
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`biphasic) profile composition of memantine (see title and abstract), wherein the dosage
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`provides an extended controlled-release profile such that the active substance can be
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`conveniently and reliable released over an extended period in at least two stages (see
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`column 2, lines 40-50). Thus, one would be motivated to provide mementine in an
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`extended release form to avoid adverse drug effects and provide a convenient and
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`reliable release of mementine. One would continue to be motivated to adjust the
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`extended release formulation for maximum avoidance of adverse drug effects. As
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`Ditzler teaches that the dose should therefor be increased more slowly and ad'usted to
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`the individual situation until the optimal effect has been reached (see page 778, right
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`column, last paragraph).
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`Conclusion
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`No claims allowed.
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`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to KENDRA D. CARTER whose telephone number is
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`(571 )272—9034. The examiner can normally be reached on 9:00 am - 5:00 pm.
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
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`supervisor, Sreeni Padmanabhan can be reached on (571) 272-0629. 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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`Application/Control Number: 11/399,879
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`Information regarding the status of an application may be obtained from the
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`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`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
`
`you have questions on access to the Private PAIR system, contact the Electronic
`
`Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a
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`USPTO Customer Service Representative or access to the automated information
`
`system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
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`Kendra D Carter
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`Examiner, Art Unit 1627
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`/SREENI PADMANABHAN/
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`Supervisory Patent Examiner, Art Unit 1627
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