111111
`
`1111111111111111111111111111111111111111111111111111111111111
`US008362085B2
`
`c12) United States Patent
`Went et al.
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 8,362,085 B2
`*Jan. 29, 2013
`
`(54) METHOD FORADMINISTERINGAN NMDA
`RECEPTOR ANTAGONIST TO A SUBJECT
`
`(75)
`
`Inventors: Gregory T. Went, Mill Valley, CA (US);
`Timothy J. Fultz, Pleasant Hill, CA
`(US); Laurence R. Meyerson, Las
`Vegas, NV (US)
`
`(73) Assignee: Adamas Pharmaceuticals, Inc.,
`Emeryville, CA (US)
`
`( *) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis(cid:173)
`claimer.
`
`(21) Appl. No.: 13/536,525
`
`(22) Filed:
`
`Jun.28,2012
`
`(65)
`
`Prior Publication Data
`
`US 2012/0264829 Al
`
`Oct. 18, 2012
`
`Related U.S. Application Data
`
`(60) Continuation of application No. 12/840,132, filed on
`Jul. 20, 2010, which is a continuation of application
`No. 12/512,701, filed on Jul. 30, 2009, now Pat. No.
`8,168,209, which is a division of application No.
`11/285,905, filed on Nov. 22, 2005, now Pat. No.
`7,619,007, said application No. 12/512,701 is a
`continuation-in-part of application No. 11/399,879,
`filed on Apr. 6, 2006, now Pat. No. 8,058,291, and a
`continuation-in-part of application No. 11/285,905.
`
`(60) Provisional application No. 60/630,885, filed on Nov.
`23, 2004, provisional application No. 60/701,857,
`filed on Jul. 22, 2005, provisional application No.
`60/635,365, filed on Dec. 10, 2004, provisional
`application No. 60/669,290, filed on Apr. 6, 2005.
`
`(51)
`
`Int. Cl.
`A01N 47128
`(2006.01)
`A01N 27100
`(2006.01)
`A61K 31117
`(2006.01)
`A61K 31115
`(2006.01)
`A61K 9100
`(2006.01)
`(52) U.S. Cl. ......................... 514/597; 514/766; 424/400
`(58) Field of Classification Search .................. 514/597,
`514/766; 424/400
`See application file for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`3,152,180 A
`10/1964 Haaf
`3,391,142 A
`7/1968 Mills eta!,
`3,992,518 A
`1111976 Chien eta!.
`4,148,896 A
`4/1979 Smith eta!.
`4,273,774 A
`6/1981 Scherm
`8/1981 Bernstein et a!.
`4,284,444 A
`4,346,112 A
`8/1982 Henkel eta!.
`4,606,909 A
`8/1986 Bechgaard et a!.
`4,663,318 A
`5/1987 Davis
`
`4,767,628 A
`4,769,027 A
`4,812,481 A
`4,839,177 A
`4,861,800 A
`4,895,841 A
`4,897,268 A
`4,904,681 A
`4,948,807 A
`5,057,321 A
`5,061,703 A
`5,061,721 A
`5,086,072 A
`5,162,346 A
`5,186,938 A
`5,190,763 A
`5,192,550 A
`5,221,536 A
`5,334,618 A
`5,358,721 A
`5,382,601 A
`5,395,626 A
`5,422,120 A
`5,422,123 A
`5,484,608 A
`5,502,058 A
`5,521,178 A
`5,601,845 A
`5,614,560 A
`5,648,087 A
`5,660,848 A
`5,726,180 A
`5,756,115 A
`5,891,885 A
`5,912,013 A
`5,919,826 A
`5,958,919 A
`6,046,232 A
`
`8/1988 Hutchinson
`9/1988 Baker et al.
`3/1989 Reischig et a!.
`6/1989 Colombo eta!.
`8/1989 Buyske
`111990 Sugimoto et a!.
`111990 Tice et al.
`2/1990 Cordi eta!.
`8/1990 Rosin eta!.
`10/1991 Edgren et al.
`10/1991 Bormann et a!.
`10/1991 Cordi eta!.
`2/1992 T rullas et al.
`1111992 Lobisch et a!.
`2/1993 Sablotsky et a!.
`3/1993 Edgren et al.
`3/1993 Edgren et al.
`6/1993 Edgren et al.
`8/1994 Lipton
`10/1994 Guittard et a!.
`111995 Nurnberg eta!.
`3/1995 Kotwal eta!.
`6/1995 Kim
`6/1995 Conte eta!.
`111996 Rudnic et al.
`3/1996 Mayer eta!.
`5/1996 Nickel eta!.
`2/1997 Buxton et al.
`3/1997 Lipton eta!.
`7/1997 Ovaert eta!.
`8/1997 Moo-Young
`3/1998 Kurihara et a!.
`5/1998 Moo-Young eta!.
`4/1999 Caruso
`6/1999 Rudnic et al.
`7/1999 Caruso
`9/1999 Olney eta!.
`4/2000 Kelleher et a!.
`(Continued)
`
`AU
`CA
`
`FOREIGN PATENT DOCUMENTS
`2002323873 B2
`112003
`2323805 A1
`9/1999
`(Continued)
`
`OTHER PUBLICATIONS
`
`Bakchine and Loft, "Memantine Treatment in Patients with Mild to
`Moderate Alzheimer's Disease: Results of a Randomised, Double(cid:173)
`Blind, Placebo-Controlled 6-Month Study" J Alzheimer's Dis 11:
`(2007) 471-479.
`
`(Continued)
`
`Primary Examiner- Sreeni Padmanabhan
`Assistant Examiner- Kendra D Carter
`(7 4) Attorney, Agent, or Firm -Wilson Sonsini Goodrich &
`Rosati
`
`ABSTRACT
`(57)
`The invention provides methods for administering meman(cid:173)
`tine to a subject. Memantine in an extended release form
`containing 22.5 to 30 mg memantine or a pharmaceutically
`acceptable salt is administered to a patient suffering from a
`neurological condition, such as Alzheimer's disease, Parkin(cid:173)
`son's disease or dementia. The extended release form
`achieves particular pharmacokinetic criteria such as change
`in plasma concentration of memantine over time and ratio of
`maximum memantine plasma concentration to mean meman(cid:173)
`tine plasma concentration.
`12 Claims, 7 Drawing Sheets
`
`IPR2015-00410
`Petitioners' Ex. 1001
`Page 1
`
`

`
`US 8,362,085 B2
`Page 2
`
`U.S. PATENT DOCUMENTS
`6,057,364 A
`5/2000 Jasys eta!.
`6,066,652 A
`5/2000 Zenner eta!.
`6,114,392 A
`9/2000 Gilad et al.
`6,183,770 B1
`2/2001 Muchin eta!.
`6,187,338 B1
`2/2001 Caruso eta!.
`6,194,000 B1
`2/2001 Smith eta!.
`6,217,905 B1
`4/2001 Edgren eta!.
`6,258,827 B1
`7/2001 Chenard et a!.
`6,284,276 B1
`9/2001 Rudnic eta!.
`6,384,083 B1
`5/2002 Ludwig eta!.
`6,392,104 B1
`5/2002 Ishii eta!.
`6,444,702 B1
`9/2002 Wang et al.
`6,479,553 B1
`1112002 McCarthy
`12/2002 Faour eta!.
`6,491,949 B2
`6,500,454 B1
`12/2002 Perce! eta!.
`9/2003 Wang et al.
`6,620,845 B2
`10/2003 Peery eta!.
`6,635,268 B2
`1112003 Evans eta!.
`6,648,083 B2
`6,662,845 B1
`12/2003 Palmer
`6,715,485 B1
`4/2004 Djupesland
`6,717,012 B2
`4/2004 Wang et al.
`6,743,211 B1
`6/2004 Prausnitz et al.
`6/2004 Fischer et al.
`6,746,689 B2
`6,764,697 B1
`7/2004 Jao eta!.
`6,770,295 B1
`8/2004 Kreilgard et a!.
`6,797,283 B1
`9/2004 Edgren eta!.
`2/2005 Wang et al.
`6,852,889 B2
`7/2005 Couch et al.
`6,913,768 B2
`6,919,373 B1
`7/2005 Lam et al.
`6,923,800 B2
`8/2005 Chen eta!.
`8/2005 Wong eta!.
`6,929,803 B2
`8/2005 D' Amato et a!.
`6,930,128 B2
`9/2005 Lautenbach
`6,939,556 B2
`6,945,952 B2
`9/2005 Kwon
`7,619,007 B2
`1112009 Went eta!.
`2002/0035105 A1
`3/2002 Caruso
`2002/0071863 A1
`6/2002 Dong et al.
`2003/0190354 A1
`10/2003 Sela
`2003/0198683 A1
`10/2003 Li eta!.
`2003/0203055 A1
`10/2003 Rao eta!.
`2004/0087658 A1
`5/2004 Moebius
`2004/0102525 A1
`5/2004 Kozachuk
`2004/0122090 A1
`6/2004 Lipon
`2004/0224020 A1
`1112004 Schoenhard
`2004/0254251 A1
`12/2004 Fire stone et al.
`2005/0020319 A1
`112005 Kim eta!.
`2005/0031651 A1
`2/2005 Gervais et a!.
`2005/0065219 A1
`3/2005 Lipton eta!.
`2005/0124701 A1
`6/2005 Went eta!.
`2005/0153953 A1
`7/2005 Trippodi-Murphy eta!.
`2005/0191349 A1
`9/2005 Boehm eta!.
`2005/0203191 A1
`9/2005 McDonald et a!.
`2005/0208132 A1
`9/2005 Sathyan et a!.
`2005/0209218 A1
`9/2005 Meyerson
`2005/0232990 A1
`10/2005 Boehm eta!.
`2005/0245460 A1
`1112005 Meyerson
`2005/0245617 A1
`1112005 Meyerson et a!.
`2005/0267176 A1
`12/2005 Barberich
`2006/0002999 A1
`112006 Yang eta!.
`2006/0020042 A1
`112006 McDonald et a!.
`2006/0051416 A1
`3/2006 Rastogi et a!.
`2006/0052370 A1
`3/2006 Meyerson
`2006/0062851 A1
`3/2006 Vergez eta!.
`2006/0063810 A1
`3/2006 Vergez eta!.
`2006/0079578 A1
`4/2006 Laurin eta!.
`2006/0142398 A1
`6/2006 Went eta!.
`2006/0159763 A1
`7/2006 Meyer eta!.
`2006/0160852 A1
`7/2006 Kimura eta!.
`2006/0189694 A1
`8/2006 Went eta!.
`2006/0198884 A1
`9/2006 Yang eta!.
`2006/0240043 A1
`10/2006 Meyerson
`2006/0246003 A1
`1112006 Kimura eta!.
`2006/0252788 A1
`1112006 Went eta!.
`2007/0065512 A1
`3/2007 Dedhiya et a!.
`2008/0260825 A1
`10/2008 Quiketal.
`2008/0279819 A1
`1112008 Went eta!.
`2010/0022659 A1
`112010 Meyerson
`2010/0047342 A1
`2/2010 Went eta!.
`
`2010/0137448 A1
`2010/0260838 A1
`2010/0266684 A1
`2010/0311697 A1
`201110059169 A1
`
`6/2010 Lipton eta!.
`10/2010 Went eta!.
`10/2010 Went eta!.
`12/2010 Went eta!.
`3/2011 Went eta!.
`
`FOREIGN PATENT DOCUMENTS
`0350080
`111990
`EP
`0392059 A1
`10/1990
`EP
`0451484 A1
`10/1991
`EP
`0452484 B2
`10/1991
`EP
`0488959 A2
`1111991
`EP
`0488959 A3
`8/1992
`EP
`0502642 A1
`9/1992
`EP
`0524968
`2/1993
`EP
`0731359
`9/1996
`EP
`0870757 A2
`10/1998
`EP
`0927711 A1
`7/1999
`EP
`0870757 A3
`6/2000
`EP
`EP
`1559418
`8/2005
`1600156
`1112005
`EP
`1509232 B1
`1112008
`EP
`2219159
`9/1974
`FR
`1173492 A
`12/1969
`GB
`58-4718
`111983
`JP
`10203966 A
`8/1998
`JP
`wo
`WO 89/09051 A1
`10/1989
`wo
`WO 91106291 A1
`5/1991
`wo
`WO 91114445 A1
`10/1991
`wo
`W0-92-17168
`10/1992
`wo
`WO 94/05275 A1
`3/1994
`wo
`WO 94/06428 A1
`3/1994
`wo
`WO 95/13796 A1
`5/1995
`wo
`W0-97-02273
`111997
`wo
`WO 97/14415 A1
`4/1997
`wo 98/07447
`wo
`2/1998
`wo
`W0-98-07447
`2/1998
`wo
`WO 98/18457 A1
`3/1998
`wo
`W0-98-15275
`4/1998
`wo
`WO 98/27961 A2
`7/1998
`wo
`WO 98/27961 A3
`9/1998
`wo
`W0-98-50044
`1111998
`wo
`W0-00-00 197
`1/2000
`wo
`W0-00-03716
`1/2000
`wo
`WO 00/18378 A1
`4/2000
`wo
`W0-00-29023
`5/2000
`wo
`W0-00-54810
`9/2000
`wo
`WO 00/56301 A2
`9/2000
`wo
`WO 00/56301 A3
`12/2000
`wo
`W0-01-08682
`212001
`wo
`WO 01119901 A2
`3/2001
`wo
`WO 01132115 A1
`5/2001
`wo
`WO 01132148 A1
`5/2001
`wo
`WO 01146291 A1
`6/2001
`wo
`WO 01162706 A1
`8/2001
`wo
`WO 01119901 A3
`9/2001
`wo
`W0-01-91753
`12/2001
`wo
`W0-03-094812
`1112003
`wo
`WO 03/101458 A1
`12/2003
`wo WO 2004/012700 A2
`2/2004
`wo WO 2004/012700 A3
`4/2004
`wo WO 2004/037234 A2
`5/2004
`wo W0-2004-056335
`7/2004
`wo WO 2004/056335 A2
`7/2004
`wo WO 2004/037234 A3
`8/2004
`wo W0-2004-087116
`10/2004
`wo WO 2004/087116 A2
`10/2004
`wo WO 2004/056335 A3
`1112004
`wo WO 2004/087116 A3
`12/2004
`wo WO 2004/112768 A1
`12/2004
`wo W0-2005-058420
`6/2005
`wo WO 2005/065645 A2
`7/2005
`wo WO 2005/072705 A1
`8/2005
`wo W0-2005-079773
`9/2005
`wo WO 2005/079773 A2
`9/2005
`wo W0-2005-079779
`9/2005
`wo W0-2005-084655
`9/2005
`wo WO 2005/065645 A3
`10/2005
`wo WO 2005/079773 A3
`10/2005
`
`IPR2015-00410
`Petitioners' Ex. 1001
`Page 2
`
`

`
`US 8,362,085 B2
`Page 3
`
`wo
`wo
`wo
`wo
`wo
`wo
`
`WO 2005/092009 A2
`WO 2006/009769 A1
`WO 2005/092009 A3
`WO 2006/070781 A1
`WO 2006/089494 A1
`WO 2006/138227 A1
`
`10/2005
`112006
`2/2006
`7/2006
`8/2006
`12/2006
`
`OTHER PUBLICATIONS
`
`Carlton, S.M., Hargett, G.L., Treatment with the NMDA antagonist
`memantine attenuates nociceptive responses to mechanical stimula(cid:173)
`tion in neuropathic rats. Neurosci. Lett. 198, ll5-ll8. (1995).
`Eisenberg, E., LaCross, S., Strassman, M. The clinically tested
`N-methyl-D-aspartate receptor antagonist memantine blocks and
`reverses
`thermal hyperalgesia
`in a
`rat model of painful
`mononeuropathy. Neurosci. Lett. 187,17-20 (1995).
`Johannsen P. "Long-Term Cholinesterase Inhibitor Treatment of
`Alzheimer's Disease" CNS Drugs (2004) 18(12):757-68.
`Keilhoff et al., Memantine prevents quionlinic acid-induced hip(cid:173)
`pocampal damage. Eur. J. Pharmacol. 219:451-454, (1992).
`Kornhuber and Quack. "Cerebrospinal fluid and serum concentra(cid:173)
`tions of the N-methyl-D-aspartate (NMDA) receptor antagonist
`memantine in man," Neurosci. Letters, 195:137-139 (1995).
`Lanctot et a!, "Efficacy and safety of cholinesterase inhibitors in
`Alzheimer's disease: a meta-analysis" Canadian Medical Associa(cid:173)
`tion Journal (2003) 169:557-64.
`Lipton et a!., Excitatory Amino Acids as a Final Common Pathway
`for Neurologic Disorders, N. Engl. J. Med, 330(9) :613-622 (1994).
`Neugebauer, V., Kornhuber, J., Lu eke, T., Schaible, H.G., The clini(cid:173)
`cally available NMDA
`receptor antagonist memantine
`is
`antinociceptive on rat spinal neurones. Neuroreport 4, 1259-1262.
`(1993).
`Parsons CG, Gruner R, Rozental J, Millar J, Lodge D. Patch clamp
`studies on the kinetics and selectivity ofN -methyl-D-aspartate recep(cid:173)
`tor antagonism by memantine, (1-amino-3 ,5-dimethyladarnantan).
`Neuropharmacology ;32: 1337-1350 (1993).
`Parsons, at a!., 2001) NMDA receptors as targets for drugs in
`neuropathic pain. Eur. J. Pharmacology, 429, 71-78 (2001).
`Rogers et al., A 24-week, double-blind, placebo-controlled trial of
`donepezil in patients with Alzheimer's disease, Neurology (1998)
`50:136-45.
`Sobolevsky AI, Koshelev SG, Khodorov BI. Interaction with agonist(cid:173)
`unbound NMDA-receptor channels in acutely isolated rat hip(cid:173)
`pocampal neurons. J Physiol (1998) 512(Pt 1).47-60.
`Winblad eta!., "A 1-year, randomized, placebo-controlled study of
`donepezil in patients with mild to moderate AD," Neurology (2001)
`57 :489-95.
`EP 1874282 Patentee's Written Submissions Under Rule ll6 EPC
`dated Sep. 7, 2012.
`Reichman, "Current pharmacologic options for patients with
`Alzheimer's disease," Annals of General Hospital Psychiatry, vol. 2,
`pp. 1-14 (2003).
`Wilcock G. Mobius HJ, Stoffier A; MNIM 500 group. A double(cid:173)
`blind, placebo-controlled multi centre study of memantine in mild to
`moderate vascular dementia (MMM500). Int Clin Psychopharrnacol.
`Nov. 2002;17(6):297-305.
`Anand et a!., "Dissolution Testing: An FDA Perspective," AAPS
`Workshop, Physical PharmacyandBiopharrnaceutics, May 13,2009,
`1-32.
`Bashki et al., "Fatigue in Multiple Sclerosis and Its Relationship to
`Depression and Neurologic Disability," Mult Seier 6:181-5 (2000).
`Ing eta!., "Toxic Effects of Amantadine in Patients with Renal Fail(cid:173)
`ure," CMA Journal, Mar. 1979, vol. 120. pp. 695-697.
`Mann, "The Medical Management of Depression," New England
`Journal of Medicine, 353 :1819-34 (2005).
`Siegert eta!., "Depression in Multiple Sclerosis; a review," J Neurol
`Neurosurg Psychiatry 76:469-75 (2005).
`Almeida et a!., "Evidence for the involvement of L-arginine-nitric
`oxide-cyclic guanosine monophosphate pathway in the antidepres(cid:173)
`sant-like effect ofmemantine in mice" Behavioural Brain Research,
`vol. 168, No.2, Apr. 2006, pp. 318-322, XP002445450 ISSN: 0166-
`43128.
`
`Bonnet, "Involvement of non -dopaminergic pathways in Parkinson's
`disease: Pathophysiology and therapeutic implications" CNS Drugs,
`vol. 13, No. 5, May 2000, pp. 351-364, XP009068859 ISSN: ll72-
`7047.
`Delagarza eta!., "Parmacologic Treatment of Alzheimer's Disease:
`an Update," Am. Fam. Phys. vol. 68, No. 7, 2003, pp. 136-572.
`Dong et a!., "Acetylcholinesterase inhibitors ameliorate behavioral
`deficits in the Tg2576 mouse model of Alzheimer's disease,"
`Psychopharmacology vol. 181, No. 1, 2005, pp. 145-152.
`Engber, et al., "NMDA receptor blockade reverses motor response
`alterations induced by levodopa" Neuroreport, vol. 5, No. 18, 1994,
`pp. 2586-2588, XP009068863 ISSN: 0959-4965.
`Franz et al., "Percutaneous Absorption on the Relevance ofln Vitro
`Data," J. Invest. Derm. vol. 64, 1975, pp. 194-195.
`Fredriksson eta!., "Co-administration of memantine and amantadine
`with sub/suprathreshold doses of L-Dopa restores motor behaviour
`of MPTP-treated mice" Journal of Neural Transmission, vol. 108,
`No.2, 2001, pp. 167-187, XP002389118 ISSN: 0300-9564.
`Greenamyre eta!., "Anti parkinsonian effects of remacemide hydro(cid:173)
`chloride, a glutamate antagonist, in rodent and primate models of
`Parkinson's disease" Annals of Neurology, vol. 35, No.6, 1994, pp.
`655-661, XP009068858 ISSN: 0364-5134.
`Jost, "Therapy in the early stage of idiopathic Parkinson's disease"
`Nervenheilkunde 2005 Germany, vol. 24, No. 1, 2005, pp. 24-28,
`XP009046893 ISSN: 0722-1541 with English Summary.
`Koch et al., "Anodic Chemistry of Adarnantyl Compounds. Some
`Scissible Carbon, Halogen, Hydrogen, and Oxygen Substituents"
`Journal of the American Chemical Society., vol. 95, No. 26, Dec. 26,
`1973, pp. 8631-8637, XP002170382 American Chemical Society,
`Washington, DC., US ISSN: 0002-7863.
`Kotani et a!., "A New Combined Oxidizing Reagent System,
`Hexakisacetonitrile Iron(III) periodate: Oxidation ofParrafin Hydro(cid:173)
`carbons" Chemical and Pharmaceutical Bulletin, vol. 33, No. 11 ,
`Nov. 1985, pp. 4680-4684, XP002170380 Tokyo JP.
`Mastrosimone et al.,"Personal Experience With a Combination of
`Drugs in Subjects With Dopa Resistand Parkinson's Disease" Journal
`ofMedicine, Karger, Basel, CH, vol. ll, No. 5/6, 1980, pp. 377-383,
`XP009038480 ISSN: 0025-7850.
`Mella et al., "Oxidative-Functionalization of Adamantane and Some
`oflts Derivatives in Solution" Journal of Organic Chemistry., vol. 61,
`No. 4, 1996, pp. 1413-1422, XP002170381 American Chemical
`Society. Easton., US ISSN: 0022-3263.
`Merims D et a!., "Riluzole for le vodopa-induced dyskinesias
`advanced Parkinson's disease" Lancet The, Lancet Limited. London,
`GB, vol. 153, No. 9166.22 May 1999, pp. 1764-1765, XP004826824
`ISSN: 0140-6736.
`Metman L Verhagen eta!., "Amantadine as treatment for dyskinesias
`and motor fluctuations in Parkinson's disease" Neurology, vol. 50,
`No.5, May 1998, pp. 1323-1326, XP009068857 ISSN: 0028-3878.
`Metman et a!., "A Trial of Dextromethorphan in Parkinsonian
`Patients With Motor Response Complications" Movement Disor(cid:173)
`ders, Raven Press, New York., NY, US, vol. 13, No.3, May 1998, pp.
`414-417, XP009066519 ISSN 0885-3185.
`Papa et al., "Levodopa-Induced Dyskinesia Improved by a Glutamate
`Antagonist in Parkinsonian Monkeys" Annals ofNeurology, Boston,
`US, vol. 39, May 1996, pp. 574-578, XP002090027 ISSN: 0364-
`5134.
`Parsons et a!.: 'Glutamate in CNS disorders as a target for drug
`development: an update', XP002908604 Retrieved from STN Data(cid:173)
`base accession No. 131:13198 & Drug News Perspect. vol. ll, No.9,
`1998, pp. 523-569.
`Rogoz eta!., "Synergistic effect ofuncompetitive NMDA receptor
`antagonists and antidepressant drugs in the forced swimming test in
`rats" Neuropharmacology, Pergamon Press, Oxford, GB, vol. 4 2, No.
`8, Jun. 2002, pp. 1024-1030, XP002288820 ISSN: 0028-3908.
`Shefrin, "Therapeutic advances in idiopathic Parkinsonism" Expert
`Opinion on Investigational Drugs 1999 United Kingdom, vol. 8, No.
`10, 1999, pp. 1565-1588, XP002389ll9 ISSN: 1354-3784.
`Shuto Satoshi eta!., "(1S,2R)-1-Phenyl-2-A(S)-1-aminopropy!U-N,
`N-diethylcyclopropane-carbox amide )PPDC) a New Class of
`NMDA-Receptor Antagonist: Molecular Design by a Novel
`Conformational Restriction Strategy" Japanese Journal of Pharma-
`
`IPR2015-00410
`Petitioners' Ex. 1001
`Page 3
`
`

`
`US 8,362,085 B2
`Page 4
`
`cology, The Japanese Pharmacological Society, Kyoto, JP, vol. 85,
`No.3, Mar. 2001, pp. 207-213, XP008021088 ISSN: 0021-5198.
`Snijdelaar eta!., "Effects ofPerioperative Oral Amantadine on Post(cid:173)
`operative Pain and Morphine Consumption in Patients after Radical
`Prostatectomy: Results of a Preliminary Study" Anesthesiology 2004
`United States, vol. 100, No.1, Jan. 2004, pp. 134-141, XP009057749
`ISSN: 0003-3022.
`Spieker et al.,"The NMDA antagonist budipine can alleviate
`levodopa-induced motor fluctuations." Movement Disorders : Offi(cid:173)
`cial Journal of the Movement Disorder Society, May 1999, vol. 14,
`No.3, May 1999, pp. 517-519, XP009068946 ISSN: 0885-3185.
`Sviridov eta!., 'C-hydroxyalkylation of N-adamantylanilines with
`hexafluoroacetone and methyl trifluoropyruvate', XP002958124
`Database CAPLUS [Online] Retrieved from STN Database acces(cid:173)
`sion No. 1990:197720 & Izv. Akad. NAUK SSSR, Ser. Khim. No. 10,
`1989, pp. 2348-2350.
`"Antiparkinsonian drugs memantine and
`Urbanska et a!.,
`trihexylphenidyl potentiate the anticonvulsant activity of valproate
`against maximal electroshock-induced seizures" Neuropharmacol(cid:173)
`ogy, vol. 31, No. 10, 1992, pp. 1021-1026, XP002332724.
`Van Dam et a!. "Symptomatic effect of donepezil, rivastigmine,
`galatamine and memantine on cognitive deficits in the APP23
`model," Psychopharmacology vol. 180, No. 1, 2005, pp. 177-190.
`Weileret al., "The use ofPropranolol in Alzheimer's Disease Patients
`with Disruptive Behavior" Current Therapeutic Research, vol. 42,
`No.2, Aug. 1987, pp. 364-374, XP001027133.
`Wessell, et a!., "NR2B selective NMDA receptor antagonist
`CP-101,606 prevents levodopa-induced motor response alterations
`in hemi-parkinsonian rats" Neuropharmacology, vol. 47, No.2, Aug.
`2004, pp. 184-194, XP002389117 ISSN: 0028-3908.
`Zarate eta!. "A double-blind, placebo-controlled study of memantine
`in the treatment of major depression" American Journal of Psychia(cid:173)
`try, vol. 163, No. 1, Jan. 2006, pp. 153-155, XP009087802
`ISSN:0002-953X.
`PCT/US2005/042780 International Search Report dated Sep. 8,
`2006.
`EP 05852057 (EP 1827385 A) Third Party Submission Undet Art.
`115 EPC dated May 25, 2012.
`Maier et al., "Efficacy of the NMDA-receptor antagonist memantine
`in patients with chronic phantom limb pain-results of a randomized
`double-blinded, placeo-controlled trial," Pain, 103, pp. 277-283
`(2003).
`Namenda label, NDA 21-487, pp: 1-20. Forest Pharmaceuticals, Inc.
`(2007).
`Pharmaceutical Dosage Forms: Tablets, Second Edition, Revised and
`Expanded, published by Marcel Dekker, Inc., edited by Lieberman,
`Lachman, and Schwartz. (1990) pp. 462-472.
`Remington, The Science and Practice of Pharmacy, 21 sr Ed., pp.
`944-945 (2006).
`Swerdlow et al., "The Effects ofMemantine on Prepulse Inhibition,"
`Neuropsychopharmacology, 34, pp. 1854-1864 (2009).
`Vale eta!., "Amantadine in Depression," Lancet, 11,437 (1971).
`International search report dated Apr. 5, 2002 for PCT Application
`No. US2001/48516.
`International search report dated May 8, 2006 for PCT Application
`No. US2005/42424.
`"Pharmazeutische Technologie" 51
`h Ed. w/ English Translation
`(1997).
`
`(2000).
`Annex A (Letter from Mint Levin dated Jan. 27, 2009) from Oral
`Proceedings request of May 30, 2012.
`Annex B (Additional data) from Oral Proceedings request of May 30,
`2012.
`EP1874282 (Appl. No. 06749777.6) OppositionAgainstPatentdated
`Jun. 10,2011.
`EP1874282 (Appl. No. 06749777.6)0ral Proceedings Request dated
`May30,2012.
`EP1874282 (Appl. No. 06749777.6) Granted Patent Claims(cid:173)
`granted Sep. 15, 2010.
`2006 Chemical Abstracts Service. Catalog. Published 2006 by
`Chemical Abstracts Service, p. 52.
`
`"PharmazeutischeTechnologie" 91h Ed. w/ English Translation
`
`Ambrozi, et a!. Treatment of Impaired Cerebral Function in
`Psychogeriatric Patients with Memantine-Results of a Phase II
`Double-Blind Study. Pharmacopsychiat. 1988:21(3);144-6.
`Avery's Drug Treatment; Principles and Practice of Clinical Pharma(cid:173)
`cology and Therapeutics, 3rd Edition, 1987, edited by Trevor M.
`Speight, Chapter VIII, pp. 255-282.
`Barth eta!. Combination therapy with MK-801 and alpha-phenyl(cid:173)
`tert-butyl-nitrone enhances protection against ischemic neuronal
`damage in organotypic hippocampal slice cultures. Exp Neurol.
`1996; 141(2):330-6.
`Bayer!, et al. Klinsche Vergleichsstudie der Antispastika Memantin
`und Baclofen. (Clinical Comparative Study of the Antispastic Com(cid:173)
`pounds Memantine and Baclofen). Therapiewozhe 1988;35: 5440-
`5444, (with English abstract).
`Beers, M.H. and Berkow, R. Editors-in-chief, The Merck Manual of
`Diagnosis and Therapy, 17th Edition, pp. 1525-1544,1999.
`Bentue-Ferrer, et al. Medication in Alzheimer's disease, Rev. Geriatr.
`26(6):511-522 (2001), (in French with English summary).
`Berman, et al. Antidepressant effects of ketamine in depressed
`patients. Bioi, Psychiatry. 2000;47:351-354.
`Bhat, eta!. Localization of the N-methyl-D-aspartate Rl receptor
`subunit in specific anterior pituitary hormone cell types of the female
`rat. Neuroendocrinol. 1995;62(2): 178-186.
`Bliss, eta!. A synaptic model of memory: long-term potentiation in
`the hippocampus. Nature. 1993;361:31-39.
`Bormann, J. Memantine is a potent blocker ofN-methyl-D-aspartate
`(NMDA) receptor channels. Eur. J. Pharmacol. 1989;166:591-592.
`Braga, et a!. Making crystals from crystals: a green route to crystal
`engineering and polymorphism, Chemical Communications pp.
`3635-3645 (2005).
`Bredt, eta!. Localization of nitric oxide synthase indicating a neural
`role for nitric oxide. Nature. 1990;347:768-770.
`Budziszewska, et a!. Antidepressant drugs inhibit glucocorticoid
`receptor-mediated gene transcription-a possible mechanism, Br J
`Pharmacol. Jul. 2000;130(6):1385-93.
`Bull, Drug review-Memantine, Drugs in Context 2005, I(I): 1-40.
`Cacabelos, et al. Pharmacological treatment of Alzheimer disease:
`inhibitors
`to
`from psychotropic drugs and cholinesterase
`pharmacogenomics. Drugs Today. 2000; 36(7):415-499.
`Calbabrese, et a!. A double-blind placebo-controlled study of
`lamotrigine monotherapy in outpatients with bipolar 1 depression.
`Lamictal602 Study Group. J. Clin. Psychiatry, 1993;60:79-88.
`Camps, et al. Cholinergic drugs in pharmacotherapy of Alzheimer's
`disease. Mini Rev Med Chern. Feb. 2002;2(1): 11-25.
`Chamulitrat, et al. Nitric oxide formation during light-induced
`decomposition of phenyl N-tert-butylnitrone. J. Bioi. Chern. 1993;
`268(16): 11520-11527.
`Chen, et a!. Mechanism of memantine block of NMDA-activated
`channels in rat retinal ganglion cells: uncompetitive antagonism. J.
`Physiol. 1997; 499(1):27-46.
`Chen, et al. Neuroprotective concentrations of the N-methyl-D(cid:173)
`aspartate open-channel blocker memantine are effective without
`cytoplasmic vacuolation following post-ischemic administration and
`do not block maze learning or long-term potentiation. Neurosci.
`1998; 86(4):1121-1132.
`Chen, eta!. Open-channel block ofN-methyl-D-aspartate (NMDA)
`reponses by memantine: therapeutic advantage against NMDA
`receptor-mediated neurotoxicity. J. Neurosci. 1992; 12( 11 ):4427-
`4436.
`Choi, DW. Glutamate neurotoxicity and diseases of the nervous
`system. Neuron. 1988;1:623-634.
`Chung, eta!. Clinical pharmacokinetics of doxazosin in a controlled(cid:173)
`release gastrointestinal therapeutic system (GITS) formulation; Br J
`Clin Pharmacoll999, 48:678-87.
`Cohan, et al. Electrically and chemically mediated increases in
`intracellular calcium in neuronal growth cones. J. Neurosci.
`1987;7(11):3588-3599.
`Connor, et. a!. Depolarization- and transmitter-induced changes in
`intracellular Ca2+ of rat cerebellar granule cells in explant cultures.
`J. Neurosci. 1987;7(5): 1384-1400.
`Connor, et at. Sustained dendritic gradients of Cal+ induced by
`excitatory amino acids in CAl hippocampal neurons. Science.
`1988;240( 4852):649-53.
`
`IPR2015-00410
`Petitioners' Ex. 1001
`Page 4
`
`

`
`US 8,362,085 B2
`Page 5
`
`Cummings, J. L. Depression and Parkinson's Disease: A Review. The
`American Journal of Psychiatry. 1992;149(4): 443-454.
`Cutler, RG. Human longevity and aging: possible role of reactive
`oxygen species. Ann. NewYorkAcad. Sci. 1991;621:1-28.
`Danysz, et a!. Arninoadamantanes as NMDA receptor antagonists
`and antiparkinsonian agents-preclinical
`studies. Neurosci.
`Biobehav. Rev. 1997:21(4):455-468.
`Danysz, eta!. Memantine provides neuronprotection in animal mod(cid:173)
`els at therapeutically relevant doses. Abstracts from the 8th Interna(cid:173)
`tional Conference on Alzheimer's Disease and Related Disorders.
`Stockholm. Sweden. Jul. 20-25, 2002, No. 297.
`Ditzler, K. Efficacy and Tolerability of Memantine in Patients with
`Dementia Syndrome, Arnzneim.-Forsch./Drug Res. 41 (II), Nr. 8,
`773-780 (1991), Bad Krozingen, Germany.
`Dooley, eta!. Donepezil: A review of its use in Alizheimer's Disease,
`Drugs and Aging 16(3)199-226 (2000).
`Dreyer, eta!. HIV-1 coat protein neurotoxicity prevented by calcium
`channel antagonists. Science. 1990;248:364-367.
`Edamatsu, eta!. The spin-trap N-tert-alpha-phenyl-butylnitrone pro(cid:173)
`longs the life span of the senescence accelerated mouse. Biochem.
`Biophys. Res. Commun. 1995;211(3);847-849.
`Edwards, K.R. New Studies on the Pharmacologic Treatment of
`Painful Neuropathies,
`Especially
`in
`Painful Diabetic
`Polyneuropathy, 52nd Annual Meeting of the American Academy of
`Neurology, Apr. 29-May 6, 2000, San Diego, CA, http://www.
`medscape.corn/viewarticle/420246.
`Eisenberg, eta!. The effects of the clinically tested NMDA receptor
`antagonist memantine on carrageenan-induced thermal hyperalgesia
`in rats. Eur. J. Pharmacol. 1994;255(1-3): 123-9.
`Eisenberg, et a!. The NMDA antagonist Memantine blocks pain
`behavior in a rat model of formalin-induced facial pain. Pain.
`1993;54(3):301-7.
`European search report dated Oct. 15, 2007 for Application No.
`07000173.0.
`European Search Report for EP 01 99 0191, mailed May 26, 2004.
`FDA Medical Review for Namenda,RTM. NDA 21-487, Oct. 2,
`2003, pp. 1-113.
`Feldman; et al. A 24-Week, randomized double-blind study of
`donepezil in moderate to severe Alzheimer's Disease, Neurology
`57:613-20 (2001).
`Fischer, eta!. The effect of intravenous administration of memantitie
`in parkinsonian patients
`(author's
`translation). Arzneimit(cid:173)
`telforschung. 1977;27(7)1487-1489 (in German with English).
`Fleischhacker, eta!. Memantine in the treatment of senile dementia of
`the Alzheimer type. Prog.Prog Neuropsychopharmacol Bioi Psy(cid:173)
`chiatry. 1986; 10( 1 ):87 -93.
`Forst!, H. Symptomatic therapy of Alzheimer dementia, Wien Med
`Wochenschr. 2002;152(3-4);77-80 (in German with English transla(cid:173)
`tion).
`Foster, et al.Neuroblology. Taking apart NMDA receptors. Nature.
`1987 ;329(6138)395-6.
`Fox, eta!. Memantine combined with an acetyl cholinesterase inhibi(cid:173)
`tor-hope for
`the
`future? Neuropsychiatr Dis Treat. Jun.
`2006;2(2): 121-5.
`Fuchsbehger, eta!. Starting Alzheimer therapy in early stages when(cid:173)
`ever possible. Activities of daily living remain intact longer, MMW
`Fortschr Med., 144(20):36-9 (2002); (in German with English sum(cid:173)
`mary).
`Galli, et al. Acetylcholinesterase inhibition and protection by
`dizocilpine (MK-801) enantiomers. J Pharm Pharmacol, Jan.
`1996;48( 1 ):71-6.
`Garthwaite, et a!. Endothelium-derived relaxing factor release on
`activation ofNMDA receptors suggests role as intercellular messen(cid:173)
`ger in the brain. Nature, 1988;336(6197):385-8.
`Gauthier, et a!. Effects of memantine on behavioural symptoms in
`Alzheimer's disease patients: an analysis of the Neuropsychiatric
`Inventory (NPI) data of two randomised, controlled studies. Int J
`Geriatr Psychiatry, May 2005;20(5):459-64.
`Gauthier, et a!. Functional, Cognitive, and Behavioral Effects of
`Donepezil in Patients with Moderate Alzheimer's Disease, Current
`Medical Research and Opinion® 18(6): 347-54 (2002).
`Gelvan et a!. Cardiac reperfusion damage prevented by a nitroxide
`free radical. Proc. Nat!. Acad. Sci. USA. 1991;88(10:4680-4.
`
`Gortelmeyer, et al., Memantine in the Treatment of Mild to Moderate
`Dementia Syndrome, Arnzneim.-Forsh./ Drug Res. 42 (II), Nr. 7,
`904-913 (1992), Frankfurt, Germany.
`Graham, et a!. Plasma homocysteine as a risk factor for vascular
`disease. The European Concerted Action Project.JAMA. 1997
`277(22): 1775-1781.
`Greenberg, et a!. Treatment of Major Depression and Parkinson's
`Disease with Combined Phenelzine and Amantadine. Am. J. Psychia(cid:173)
`try. 1985:142(2):273-274.
`Greene, T.W. Protective Groups in Organic Synthesis. John Wiley &
`Sons; pp. 70-71 (1981).
`Grossmann, et al. Memantine and neurogenic bladder disorders in
`spastic clinical pictures, Arzneim.-Forsch./Drug Res. 1982,
`32(II)(10):1273-6. (in German with English Sunrmary).
`Grynkiewicz, eta!, A new generation of Ca2+ indicators with greatly
`improved fluorescence properties. J. Bioi. Chern. 1985:260(6)3440-
`3450.
`Gupta, et a!. Novel effects of memantine in antagonizing acute
`aldicarb toxicity: Mechanistic and applied considerations. Drug
`development research. 1991; 24:329-341.
`Gupta, eta!, Prevention and antagonism of acute carbofuran intoxi(cid:173)
`cation by memantine and atropine, J Toxicol Environ Health,
`1989;28( 1 ): 111-22.
`Halm, et a!. Central manrmalian neurons normally resistant to
`glutamate toxicity are made sensitive by elevated extracellular Ca2 +:
`toxicity is blocked by theN -methyl-D-aspartate antagonist MK-80 1.
`Proc. Nat!. Acad. Sci. USA. 1998;:85(17):6556-60.
`Hartmann, et a!. Tolerability of memantine in combination with
`cholinesterase inhibitors
`in Alzheimers disease and vascular
`dementia. Abstracts from the 8th International Conference on
`Alzheimer's Disease and Related Disorders. Stockholm, Sweden.
`Jul. 20-25, 2002. No. 317.
`Hartmann, et a!. Tolerability of memantine in combination with
`cholinesterase
`inhibitors
`in dementia
`therapy.
`Int. Clin,
`Physchopharrnacol, 2003, 18(2):81-85.
`Helmuth, L. New Alzheimer's treatments that may ease the mind.
`Science. Aug. 23, 2002;297(5585)1260-2.
`Ho, et a!. Memantine: A New Treatment Option for Patients with
`Moderate-to-Severe Alzheimer's Disease, P&T, vol. 29 No. 3, Mar.
`2004.
`Hoffmann, et al. Eight-year prescription trends of memantine and
`cholinesterase inhibitors among persons 65 years and older in Ger(cid:173)
`many. Int Clin Psychopharmacol. Jan. 201 0;25( 1 ):29-36.
`Ihl, R. Dementing disorders. What benefits do the new anti -dementia
`drugs have? MMW Fortschr Med. May 6, 2002;Suppl 2:24-6, 28-9
`(in German with English translation).
`International search recort dated Apr. 5, 2002 for PCT Application
`No. US2001/48516.
`International Search Report for PCT/US2006/013506, mailed Jan.
`12, 2