IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SHIRE DEVELOPMENT LLC
`Petitioner
`v.
`LCS GROUP, LLC
`Patent Owner
`
`U.S. Patent No. 8,318,813 to Sanfilippo
`Issue Date: November 27, 2012
`Title: Method of Treating Binge Eating Disorder
`
`Inter Partes Review
`
`Inter Partes Review for U.S. Patent No. 8,318,813 Under
`Petition
`35 U .. S.C. §§ 311-319 and 37
`§§ 42.1-.80, 42.100-.123
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`Box 1450
`Alexandria,
`
`1 1450
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SHIRE DEVELOPMENT LLC
`Petitioner
`v.
`LCS GROUP, LLC
`Patent Owner
`
`U.S. Patent No. 8,318,813 to Sanfilippo
`Issue Date: November 27, 2012
`Title: Method of Treating Binge Eating Disorder
`
`Inter Partes Review
`
`Inter Partes Review for U.S. Patent No. 8,318,813 Under
`Petition
`35 U .. S.C. §§ 311-319 and 37
`§§ 42.1-.80, 42.100-.123
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`Box 1450
`Alexandria,
`
`1 1450
`
`
`
`I.
`
`MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(l) .......................... l
`
`TABLE OF CONTENTS
`
`A.
`
`B.
`
`C.
`
`D.
`
`Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(l) ............................ 1
`
`Related Matters Under 37 C.F.R. § 42.8(b)(2) ..................................... 1
`
`Lead and Back-Up Counsel Under 37 C.F.R. § 42.8(b)(3) .................. 1
`
`Service Information ............................................................................... 2
`
`II.
`
`PAYMENT OF FEES UNDER 37 C.F.R. § 42.103 ....................................... 2
`
`III. GROUNDS FOR STANDING UNDER 37 C.F.R. § 42.104(a) ..................... 2
`
`IV. CHALLENGE UNDER 37 C.F.R. § 42.104(b) AND RELIEF
`REQUESTED .................................................................................................. 2
`
`V.
`
`SUMMARY OF THE '813 PATENT ............................................................. 3
`
`A.
`
`Brief Description ................................................................................... 3
`
`Summary of the Prosecution History of the '813 Patent ..................... .4
`
`VI.
`
`STATE OF
`
`ART ..................................................................................... 5
`
`VII. PERSON
`
`ORDINARY SKILL IN THE ART .......................................... 9
`
`CLAIM CONSTRUCTION ............................................................................ 9
`
`IX. MANNER OF APPL YING CITED PRIOR ART TO EVERY
`CLAIM FOR WHICH
`IS REQUESTED ............................................... 11
`
`A.
`
`The Cited References Qualify as Prior Art ......................................... 11
`
`1.
`
`Appolinario (Ex. l 020) .............................................................. 12
`
`Mickle
`
`1023) ...................................................................... 12
`
`1024) .................................................................. .
`
`1
`
`5.
`
`Ong
`
`1017)
`
`1
`
`........ 13
`
`
`
`6.
`
`7.
`
`DSM-IV-TR (Ex.1010) ............................................................. 13
`
`Dukarm (Ex.1019) .................................................................... 13
`
`B.
`
`Ground 1: Claims 1-5, 8-10, 12, and 13 Are Unpatentable
`Under 35 U.S.C. § 103(a) over Appolinario in View of
`Mickle .................................................................................................. 13
`
`1.
`
`Appolinario Teaches that Centrally Acting Anti(cid:173)
`Obesity Agents Can Be Used to Treat BED
`Diagnosed According to DSM-IV-TR ...................................... 13
`
`Mickle Discloses LDX Dimesylate as a Centrally
`Acting Anti-obesity Agent Having Desirable
`Properties .................................................................................. 15
`
`3.
`
`Appolinario in View of Mickle Renders the
`Treatment of BED with LDX Dimesylate Obvious ................. 16
`
`C.
`
`Ground 2: Claims 6 and 7 Are Unpatentable Under 35
`U.S.C. § 103(a) over Appolinario in View of Mickle and
`
`Ground 3: Claim 11 Is Unpatentable Under 35 U.S.C.
`§ 103(a) over Appolinario in View of Mickle and Grilo .................... 25
`
`Unpatentable
`10, 12, and 13
`Ground 4: Claims 1-5,
`Under 35 U.S.C. § 103(a) over Ong in View of DSM-IV-
`and Mickle ..................................................................................... 26
`
`Combination of Ong and DSM-IV-TR
`the Diagnosis of BED and Its Treatment
`Using Stimulants ....................................................................... 26
`
`Ong Motivates the POSA to Search for an
`Improved Stimulant, and Mickle Provides the
`Solution ..................................................................................... 28
`
`1.
`
`2.
`
`3.
`
`u
`
`
`
`F.
`
`G.
`
`H.
`
`I.
`
`J.
`
`Ground 5: Claims 6 and 7 Are Unpatentable Under 35
`U.S.C. § 103(a) over Ong in View of DSM-IV-TR,
`Mickle, and Marrazzi .......................................................................... 37
`
`Ground 6: Claim 11 is Unpatentable Under 35 U.S.C.
`§ 103(a) over Ong in View of DSM-IV-TR, Mickle, and
`Grilo ..................................................................................................... 38
`
`Ground 7: Claims 1-5, 8-10, 12, and 13 Are Unpatentable
`Under 35 U.S.C. § 103(a) over Dukarm in View ofDSM-
`IV-TR and Mickle ............................................................................... 39
`
`1.
`
`2.
`
`3.
`
`The Combination ofDukarm and DSM-IV-TR
`Teaches the Diagnosis of BED and Its Treatment
`Using d-Amphetamine .............................................................. 39
`
`Mickle Addresses the Specific Problem Raised by
`Dukarm Regarding the Use of d-Amphetamine ...................... .41
`
`Dukarm in View of DSM-IV-TR and Mickle
`Renders the Treatment of BED with LDX
`Dimesylate Obvious ......................................................... .
`
`Ground 8: Claims 6 and 7 Are Unpatentable Under 35
`U.S.C. § 103(a) over Dukarm in View of DSM-IV-TR,
`Mickle, and Marrazzi .......................................................................... 50
`
`Ground 9: Claim 11 Unpatentable Under 35 U.S.C.
`§ 103(a) over Dukarm in View of DSM-IV-TR, Mickle,
`and Grilo .............................................................................................. 51
`
`S ARGUMENTS DURING PROSECUTION
`DO NOT DEMONSTRATE NONOBVIOUSNESS OF THE
`CLAIMS ....................................................................................................... .
`
`Would Have Extended Dukarm's Teachings of
`Treatment of BN to the
`of Stirn ulants
`Treatment of
`............................................................................... 53
`
`of
`the
`Motivated
`Would
`BED ......................................... .
`
`
`
`XI.
`
`SECONDARY CONSIDERATIONS ARGUED BY
`APPLICANT DURING PROSECUTION DO NOT REFUTE
`OBVIOUSNESS ............................................................................................ 57
`
`A.
`
`B.
`
`Examples 1, 2, and 5 of the '813 Patent Do Not
`Demonstrate that LDX Dimesylate Shows Surprising and
`Unexpected Efficacy for Treating BED .............................................. 57
`
`Applicant's Arguments Regarding Long-Felt Need Do
`Not Support Nonobviousness .............................................................. 59
`
`XII. CONCLUSION .............................................................................................. 60
`
`IV
`
`
`
`Exhibit Number
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`t 013
`
`1014
`
`LIST OF EXHIBITS
`
`Exhibit Name
`Patent No. 8,318,813 to Sanfili po. ("'813 atent")
`Prosecution History of U.S. Patent No. 8,318,813
`(certified) obtained from the U.S. Patent and Trademark
`Office. "'813 PH")
`July 21, 2011 Office Action for U.S. Application Serial
`No. 12/666,460.
`''Jul 2011 OA"
`January 23, 2012 Response to Office Action for U.S.
`A
`lication Serial No. 12/666,460. "Jan. 2012 Res ."
`April 18, 2012 Final Office Action for U.S. Application
`Serial No. 12/666,460. "A r. 2012 OA"
`June 18, 2012 Response to Final Office Action for U.S.
`A
`lication Serial No. 12/666,460. "June 2012 Res ."
`June 21, 2012 Examiner-Initiated Interview Summary for
`U.S. Application Serial No. 12/666,460. ("June 2012 Int.
`Sum."
`July 20, 2012 Notice of Allowance for U.S. Application
`Serial No. 12/666,460.
`''Jul 2012 NOA"
`Dr. Timothy D. Brewerton's Declaration. ("Brewerton
`Dec."
`American Psychiatric Association, Diagnostic and
`Statistical Manual of Mental Disorders, Fourth Edition,
`Text Revision. Washington, DC: American Psychiatric
`2000;
`
`al., Dopamine Transporter Genotype as a
`LH,
`for Obesity
`Risk
`Obes. Res. 2002; 10(1
`Samanin R,
`al., Neurochemical
`Anorectic Drugs. Pharmacol. Toxicol. 1993
`
`v
`
`
`
`Exhibit Number
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`Exhibit Name
`Blundell JE, et al., Serotonin and Appetite Regulation:
`Implications for the Pharmacological Treatment of
`Obesi
`. CNS Dru s. 1998; 9(6 : 473-495. ("Blundell"
`Drimmer EJ, Stimulant Treatment of Bulimia Nervosa
`With and Without Attention-Deficit Disorder: Three Case
`Re orts. Nutrition. 2003; 19 1 : 76-77. ("Drimmer"
`Ong YL, Suppression of Bulimic Symptoms with
`Methylamphetamine. Brit. J Psychiatry. 1983; 143: 288-
`293. "On "
`Sokol MS, et al., Methylphenidate Treatment for Bulimia
`Nervosa Associated with a Cluster B Personality Disorder.
`Disord. 1999; 25 2 : 233-237. "Sokol"
`Int
`Dukarm CP, Bulimia Nervosa and Attention Deficit
`Hyperactivity Disorder: A Possible Role for Stimulant
`Medication. J Womens Health. 2005; 14(4): 345-350.
`"Dukarm"
`Appolinario JC, et al., Pharmacological Approaches in the
`Treatment of Binge Eating Disorder. Curr. Drug Targets.
`2004; 5(3 ): 301-307. ("A olinario")
`Appolinario JC, et al., An Open-Label Trial of Sibutramine
`in Obese Patients with Binge-Eating Disorder. J Clin.
`chiatr . 2002; 63 1 : 28-30.
`olinario 2002"
`Milano W, et al., Use of Sibutramine, an Inhibitor of the
`Reuptake of Serotonin and Noradrenaline, in the Treatment
`Eating Disorder: A Placebo-Controlled Study.
`Adv. Ther. 2005; 22 1 :
`1. ("Milano"
`
`and
`nvri'DVC' Fourth Edition.
`
`
`
`Exhibit Name
`Fairburn CG, et al., The Natural Course of Bulimia
`Nervosa and Binge Eating Disorder in Young Women.
`Arch. Gen. Psychiatry. 2000; 57(7): 659-665. (''Fairburn
`2000"
`Fairburn CG, et al., Cognitive Behaviour Therapy for
`Eating Disorders: a "Transdiagnostic" Theory and
`Treatment. Behav. Res. Ther. 2003; 41: 509-528.
`("Fairburn 2003")
`Grilo CM, et al., Efficacy of Cognitive Behavioral Therapy
`and Fluoxetine for the Treatment of Binge Eating Disorder:
`A Randomized Double-Blind Placebo-Controlled
`Comparison. Biol. Psychiatry. 2005; 57(3): 301-309.
`"Grilo 2005"
`Arnold LM, et al., A Placebo-Controlled, Randomized
`Trial ofFluoxetine in the Treatment of Binge-Eating
`Disorder. J Clin. Psychiatry. 2002; 63(11): 1028-1033.
`"Arnold"
`American Psychiatric Association, Practice Guideline for
`the Treatment of Patients with Eating Disorders, Third
`2006. /"Practice
`National Institute for Clinical Excellence, Eating
`Disorders: Core Interventions in the Treatment and
`
`hibit Number
`
`1027
`
`1028
`
`1029
`
`1030
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`
`
`Exhibit Number
`
`1038
`
`1039
`
`1040
`
`1041
`
`Exhibit Name
`American Psychiatric Association, Diagnostic and
`Statistical Manual of Mental Disorders, Third Edition(cid:173)
`Revised. Washington, DC: American Psychiatric
`Association: 1987; 65-71. "DSM-III-R"
`Russell G, Bulimia Nervosa: An Ominous Variant of
`Anorexia Nervosa. Psycho/. Med. 1979; 9(3): 429-448.
`"Russell"
`Stunkard A, Eating Patterns and Obesity, The Psychiatry
`uarterl . 1959; 33 1 : 284-295. "Stunkard 1959"
`Messner E, Methylphenidate Treatment of Bulimia
`Nervosa After Surgery. Can. J Psychiatry. 1989; 34(8):
`824-826. "Messner"
`Schweickert LA, et al., Efficacy of Methylphenidate in
`Bulimia Nervosa Comorbid with Attention-Deficit
`Hyperactivity Disorder: A Case Report. Int. J Eat. Disord.
`i----------+--19_9_7~; 2_1 3 : 299-301. "Schweickert"
`Hudson JI, et al., The Prevalence and Correlates of Eating
`Disorders in the National Comorbidity Survey Replication.
`Biol. Ps chiatry. 2007; 61(3): 348-358. ("Hudson")
`Stunkard A, et aL, d-Fenfluramine Treatment of Binge
`Eating Disorder. Am. J Psychiatry. 1996; 153(11): 1455-
`"Stunkard 1996" .
`the
`Sibutramine
`Wilfley
`et al., Efficacy
`..-o.-.Trv...c.-.-.,,.. of
`Disorder: A Randomized
`Study.Am.
`("Wilfle "
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1048
`
`Bulimia Nervosa With Desipramine:
`Placebo-Controlled Study. Am. Psychiatry. 1990;
`147 11: 1509-1513
`
`
`
`Exhibit Number
`
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`1057
`
`Exhibit Name
`Malhotra S, et al., Venlafaxine Treatment of Binge-Eating
`Disorder Associated With Obesity: A Series of 35 Patients.
`J. Clin. Psychiatry. 2002; 63(9): 802-806. (''Malhotra")
`Schepers RJF, et al., Methamphetamine and Amphetamine
`Pharmacokinetics in Oral Fluid and Plasma after
`Controlled Oral Methamphetamine Administration to
`Human Volunteers. Clin. Chem. 2003; 49(1): 121-132.
`("Schepers")
`Sulzer, D. Mechanisms of Neurotransmitter Release by
`Amphetamines: A Review. Prog. Neurobiol. 2005; 75(6):
`406-433. ("Sulzer")
`Fleckenstein
`New Insights into the Mechanism of
`Action of Amphetamines. Annu. Rev. Pharmacol. Toxicol.
`2007; 4 7: 681-698. ("Fleckenstein")
`June 10, 2011 Response to Office Action for U.S.
`Application Serial No. 12/666,460. ("June 2011 Resp.")
`Carter WP, et al., Pharmacologic Treatment of Binge
`Eating Disorder. Int. J Eat. Disord. 2003; 34 Suppl: S74-
`S88. ("Carter")
`Cortese S, et aL, Attention-Deficit/Hyperactivity Disorder
`(ADHD) and Binge Eating. Nutr. Rev. 2007;65(9):404-
`411. ("Cortese")
`Corstorphine E, et al., Trauma and Multi-impulsivity
`Eating Disorders. Eat. Behav. 2007; 8: 23-30.
`("Corstorphine")
`Nasser JA, et al., Impulsivity and Test Meal Intake in
`Obese Binge Eating Women. Appetite. 2004; 43(3): 303-
`307. ("Nasser")
`
`the
`
`lX
`
`
`
`Shire Development LLC ("Petitioner") petitions the United States Patent and
`
`Trademark Office ("USPTO") for Inter Partes Review ("IPR") under 35 U.S.C.
`
`§ 311 et seq. and 37 C.F.R. § 42.1 et seq. of claims 1-13 of U.S. Patent No.
`
`8,318,813 ("the '813 patent") (Ex.1001 ). As explained below, there is a reasonable
`
`likelihood that Petitioner will prevail with respect to at least one of the claims
`
`challenged in this Petition.
`
`I.
`
`MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(a)(l)
`
`A.
`
`Real Party-In-Interest Under 37 C.F.R. § 42.8(b)(l)
`
`Petitioner, Shire Development LLC, is the real party-in-interest.
`
`B.
`
`Related Matters Under 37 C.F.R. § 42 .. 8(b)(2)
`
`Petitioner is
`
`aware of any other judicial or administrative -"""'"""'""""'"" ...
`
`would affect, or be affected by, a decision
`
`this proceeding.
`
`and Back-Up Counsel Under 37 C.F .. R. § 42.8(b)(3)
`
`Petitioner provides the following designation of counsel.
`
`Edgar H. Haug (Reg. No. 29,309)
`
`Backup Counsel: Sandra
`
`(Reg. No. 46, 11
`
`Russell A. Garman (Reg. No. 62,419);
`
`No. 68,151).
`
`Fifth
`
`10151.
`
`1 588-0800.
`
`l
`
`1
`
`
`
`D.
`
`Service Information
`
`Please address all correspondence and service to counsel at the address
`
`provided in Section LC. Petitioner also consents to electronic service by email at
`
`shire.ipr.813@flhlaw.com.
`
`II.
`
`PAYMENT OF FEES UNDER 37 C.F.R. § 42.103
`
`Petitioner provides herewith payment of the required fees in accordance with
`
`37 C.F.R. §§ 42.103 and 42.15(a). If any additional fees are required, the USPTO
`
`is authorized to charge such fees to Deposit Account No. 50-0320.
`
`III. GROUNDS FOR STANDING UNDER 37 C.F.R. § 42.104(a)
`
`Petitioner certifies that the '813 patent is eligible for IPR and that Petitioner
`
`is not barred or estopped from requesting IPR.
`
`CHALLENGE UNDER 37
`AND RELIEF REQUESTED
`
`§ 42.104(b)
`
`requests
`
`of claims 1-13
`
`'813 patent on the grounds set
`
`forth in the table below and requests cancellation of the claims as unpatentable.
`
`An explanation of how claims 1-13 are unpatentable under the statutory
`
`grounds identified below, including the identification of where each element can
`
`be found
`
`the
`
`prior art and relevance of that prior art, is provided in the
`
`form of text and detailed claim charts.
`
`
`
`Grounds
`
`Claims
`
`I
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`I-5, 8-IO, I2, and I3
`
`6 and 7
`
`II
`
`6 and 7
`
`11
`
`Appolinario
`Mickle
`Appolinario
`Mickle
`Marrazzi
`Appolinario
`Mickle
`Grilo
`Ong
`1-5, 8-10, 12, and 13 Mickle
`DSM-IV-TR
`Ong
`Mickle
`DSM-IV-TR
`Marrazzi
`Ong
`Mickle
`DSM-IV-TR
`Grilo
`Dukarm
`8-10, 12, and 13 Mickle
`DSM-IV-TR
`Duk arm
`Mickle
`DSM-IV-TR
`Marrazzi
`Dukarm
`Mickle
`
`1
`
`6 and 7
`
`11
`
`Prior Art
`(Ex. I 020) in view of
`(Ex I023)
`(Ex. I 020) in view of
`(Ex. I 023) in view of
`(Ex.I024)
`(Ex. I 020) in view of
`(Ex. I 023) in view of
`(Ex.1025)
`(Ex. I 0 I 7) in view of
`(Ex.1023) in view of
`(Ex.1010)
`(Ex.1017) in view of
`(Ex.1023) in view of
`(Ex.1010) in view of
`(Ex.I024)
`(Ex.1017) in view of
`(Ex.1023) in view of
`(Ex.1010) in view of
`(Ex.1025)
`(Ex.1019)
`(Ex.1023)
`(Ex.1010)
`(Ex.1019) in view of
`(Ex.1023) in view of
`(Ex. I 010) in view of
`(Ex 1024)
`view of
`(Ex.1019)
`(Ex.1023) in view of
`(Ex.1010) in view of
`(Ex.1025)
`
`view
`view of
`
`V.
`
`SUMMARY OF
`
`'813 PATENT
`
`Description
`
`The
`
`81
`
`3
`
`
`
`The '813 patent further claims methods in which the LDX dimesylate is combined
`
`with another active agent. The '813 patent discloses examples of six patients who
`
`were administered LDX dimesylate for treatment of BED and/or other disorders.
`
`(Ex.1001, '813 patent, col.19, 1.5-col.25, 1.30). The examples report that the
`
`patients who suffered from BED experienced a reduction in the number of binging
`
`episodes and/or the number of days in which binging occurred. (Id.).
`
`B.
`
`Summary of the Prosecution History of the '813 Patent
`
`The '813 patent issued on Nov. 27, 2012, from U.S. application Serial No.
`
`12/666,460, which claims priority to U.S. provisional application Serial No.
`
`60/972,046 filed on Sept. 13, 2007. (Id. at col. I, 11.4-7).
`
`In a N onfinal Office Action the claims, which were directed to a method of
`
`treating binge eating disorder with amphetamine prodrugs, were generally rejected
`
`under 35 U.S.C. § 103(a) as unpatentable over Dukarm as evidenced by The
`
`American Heritage Medical Dictionary in view of U.S. Publication No.
`
`2005/0038121
`
`2005"). (See
`
`1003, July 2011 OA, p.5). According to
`
`the Examiner, "Dukarm teaches a method of treating binge eating in patients with
`
`bulimia nervosa" by administering dextroamphetamine ...,,_ .. ;u ....... ..,
`
`(Id.) Although
`
`Duk arm
`
`was
`
`of bulimia nervosa ("BN"),
`
`it
`
`two reasons: ( 1 )
`
`(2) a
`
`4
`
`
`
`("POSA") would extend to BED the teachings of Dukarm regarding stimulant
`
`medication and decreased desire to binge. (See id. at 5-6). The Examiner relied on
`
`Mickle 2005 for the disclosure of abuse-resistant amphetamine prodrugs. (See id.
`
`at 6-7). Applicant responded by amending the claims to limit them to BED, and to
`
`recite the specific amphetamine prodrug, LDX dimesylate. (Ex.1004, Jan. 2012
`
`Resp., pp.2-5). Applicant argued that there was no motivation to apply the
`
`teachings ofDukarm to the treatment of BED, and no reasonable expectation of
`
`success that the teachings ofDukarm were applicable to BED. (See id. at 8-12).
`
`In a Final Office Action the Examiner withdrew the previous 35 U.S.C.
`
`§ 103(a) rejections "in view of Applicant's amendments" and introduced new
`
`rejection under 35
`
`§ 103( a). (See
`
`1005, Apr. 2012
`
`8). Applicant's response included arguments that LDX dimesylate shows
`
`unexpected efficacy
`
`treating
`
`and that
`
`has
`
`a long-felt and ~.L., ...... ..,..,
`
`need for a
`
`treatment. (Ex.1006, June 2012 Resp., pp.8-14). This evidence of
`
`secondary considerations was found persuasive and the application was then
`
`allowed (see
`
`1007, June 2012 Int. Sum.; Ex.1008, July 2012 NOA).
`
`VI.
`
`are
`
`clinicians have identified,
`
`and treated
`
`l
`
`as a
`
`5
`
`
`
`recurrent episodes
`
`binge eating. (See id. if 36). According to The Diagnostic
`
`and Statistical Manual of Mental Disorders (DSM)-psychiatry's preeminent
`
`diagnostic manual of mental disorders (see id. ilil 30, 120)-a recurrent episode of
`
`binge eating is the same in both BN and BED, namely an uncontrolled
`
`consumption of a definitely large amount of food in a short period of time
`
`associated with a feeling of loss of control. (Compare Ex. l 010, DSM-IV-TR, p.14
`
`with id. at 18; see also Ex.1009, Brewerton Dec. ilil 37, 99).
`
`Extensive research has mapped out a neurobiochemical explanation for the
`
`etiology of binge eating. (See Ex.1009, Brewerton Dec. ilil 51-53 ). Dysfunction of
`
`the serotonin (5-HT), dopamine (DA), and norepinephrine (NE) neurotransmitter
`
`systems
`
`the brain have been implicated in the underlying cause of eating
`
`disorders. (See
`
`1011, Ioannides-Demos, p.5). Specifically, decreased levels of
`
`these NTs play a central role in the binge eating cycle. (Ex.1012, Jimerson, p.5).
`
`This is not surprising since DA is fundamental to the regulation of food uptake (see
`
`1013, Epstein, p. l ), and stimulation of certain of these NT receptors leads to
`
`suppression of eating (see Ex. I 014, Samanin, p.4;
`
`101 Blundell, p.13). The
`
`_._ .. _ .. _._ ... _ ... ,,..., that patients diagnosed with
`
`levels of NTs and
`
`ofNTs in
`
`101
`
`101
`
`6
`
`
`
`At least since the 1980s, psychostimulants (also referred to as stimulants)
`
`have been shown over and over again to be effective in treating the symptom of
`
`binge eating in patients with BN. (See, e.g., Ex.1009, Brewerton Dec. iii! 39-45,
`
`160). The efficacy was not limited to a particular agent, but rather was associated
`
`with stimulants as a class, given the positive results obtained with
`
`methylamphetamine (see, e.g., Ex.1017, Ong, pp.3-6), methylphenidate (see, e.g.,
`
`Ex. l 018, Sokol, pp.4-6), mixed amphetamine salts (see, e.g., Ex.1016, Drimmer,
`
`pp.2-3), and d-amphetamine (see, e.g., Ex.l 019, Dukarm, pp.3-6). Such stimulants
`
`have been shown to increase NE levels and block DA reuptake (see Ex. l 011,
`
`Ioannides-Demos, p.6; see also Ex.1009, Brewerton Dec. ii 56). Stimulants
`
`therefore address low
`
`levels
`
`the brain, which is a central cause of
`
`eating. (See also
`
`1009, Brewerton Dec. ii 51).
`
`Anti-obesity agents have been shown to be effective
`
`the treatment
`
`BED, two of which are the centrally acting compounds d-fenfluramine and
`
`sibutramine. (See
`
`1020, Appolinario, p.3; see also Ex. l 009, Brewerton
`
`iii! 46-48).
`
`anti-obesity agents modulate NT levels, and therefore address the
`
`...,LL.~ .. ~ ..... NTlevels
`
`with
`
`(See
`
`1009,
`
`ilil57-
`
`1 1
`
`see
`
`Milano,
`
`7
`
`
`
`Despite the success in suppressing binge eating in BN with stimulants and in
`
`BED with centrally acting obesity agents, their use was not ideal. Although
`
`stimulants (e.g., d-amphetamine) were highly efficacious (see, e.g., Ex. I 0 I 9,
`
`Dukarm, p.2, Abstract), the risk of abuse in a patient population already
`
`susceptible to substance abuse remained a concern (see, e.g., id., p.6; see also
`
`Ex.I009, Brewerton Dec. ii I25). As for anti-obesity agents (e.g., d-fenfluramine,
`
`sibutramine ), the desired balance between safety and efficacy had not yet been
`
`struck. (See Ex. I 020, Appolinario, p.3; Ex. I 009, Brewerton Dec. iii! 79-8 I).
`
`Mickle describes LDX dimesylate, a new drug that demonstrates properties
`
`ideal for the treatment of binge eating, including BED. (See, e.g., Ex.I009,
`
`Brewerton
`
`iii! 83, I 02- I 04, I
`
`1
`
`I69-172).
`
`dimesy late is an amino
`
`acid prodrug of d-amphetamine. (See, e.g., Ex. I 023, Mickle iii! [0085], [0098],
`
`[O I23]). Upon
`
`administration this prodrug releases the standard, naturally
`
`occurring amino acid L-lysine and the stimulant d-amphetamine (See id. iii! [O 107],
`
`[0123]). A preferred indication for LDX dimesylate is as an anti-obesity agent.
`
`(See id. ii [OI24]). Significantly, clinical studies have shown LDX dimesylate to
`
`have reduced abuse potential compared to d-amphetamine. (See, e.g., id. iii! [0355](cid:173)
`
`[0360]).
`
`8
`
`
`
`VII. PERSON OF ORDINARY SKILL IN THE ART
`
`An underlying factual inquiry in an obviousness analysis includes the level
`
`of ordinary skill in the art. A POSA is "a hypothetical person who is presumed to
`
`have known the relevant art at the time of the invention." In re GP AC Inc.,
`
`57 F.3d 1573, 1579 (Fed. Cir. 1995). Several key factors may be considered in
`
`determining the level of ordinary skill in the art: "( 1) the educational level of the
`
`inventor; (2) type of problems encountered in the art; (3) prior art solutions to
`
`those problems; ( 4) rapidity with which innovations are made; ( 5) sophistication of
`
`the technology; and ( 6) educational level of active workers in the field." Daiichi
`
`Sankyo Co. v. Apotex, Inc., 501F.3d1254, 1256 (Fed. Cir. 2007). The USPTO
`
`applies
`
`analysis when making determinations of a
`
`SeeMPEP
`
`§ 214 l(II)(C).
`
`that a POSA with respect to the '813 patent would be a
`
`medical doctor (M.D.) specializing in psychiatry. This POSA would have clinical
`
`experience
`
`the diagnosis and psychopharmacology of eating disorders,
`
`specifically
`
`(See Ex.1009, Brewerton Dec.,~~ 26-28).
`
`VIII. CLAIM CONSTRUCTION
`
`In an
`
`a claim
`
`IS
`
`its "broadest
`
`light
`
`of
`
`of
`
`it appears. 37
`
`9
`
`
`
`"therapeutically effective amount." At this time, the other claim limitations should
`
`be given their plain and ordinary meanings.
`
`The term ''therapeutically effective amount" appears in independent claims
`
`1, 8, and 13. This term is properly construed as "an amount effective to decrease
`
`the symptoms of BED or an amount sufficient to significantly reduce the frequency
`
`and severity of binge eating behavior." (See Ex.1009, Brewerton Dec., ii 71). This
`
`interpretation is consistent with the specification of the '813 patent, which provides
`
`a definition of the term:
`
`The
`
`term
`
`'therapeutically effective amount' or
`
`'effective amount' means an amount effective, when
`
`administered to a human or non-human patient, to
`
`provide any therapeutic
`
`A therapeutic benefit
`
`may be an amelioration of symptoms, e.g., an amount
`
`effective
`
`the symptoms
`
`disorder or a major depressive disorder.
`
`certain
`
`circumstances a patient may not present symptoms of a
`
`condition for which the patient is being treated. Thus a
`
`therapeutically effective amount of a compound is also
`
`an amount
`
`to provide a significant positive
`
`on
`
`or
`
`eating
`
`or
`
`10
`
`
`
`(Ex. 1001, '813 patent, col.8 ll.48-61) (emphasis added). This quotation
`
`provides a definition of "therapeutically effective amount" with respect to
`
`the treatment of both BED and major depressive disorder. Because the
`
`claims of the '813 patent are directed to the treatment of BED, the bolded
`
`portions of the quotation, which relate specifically to BED, should be used
`
`for the interpretation of this claim term.
`
`The prosecution history of the '813 patent confirms this interpretation of
`
`"therapeutically effective amount." The term was added to claim 1 during
`
`prosecution, and Applicant asserted that support for the amendment could be found
`
`in the above-quoted paragraph. (See Ex.1004, Jan. 20 Resp., p.2, 6).
`
`CITED PRIOR ART
`EVERY CLAIM FOR WHICH IPK IS REQUESTEU
`
`this Section, Petitioner proposes various grounds for canceling claims 1-
`
`13, and thus explains the justification for IPR. Petitioner presents the following
`
`arguments and claim charts demonstrating that the claims are unpatentable under
`
`Section IV above.
`
`The
`
`references relied on in the statutory grounds all qualify as prior art as
`
`laid out below.
`
`11
`
`
`
`1.
`
`Appolinario (Ex.1020)
`
`Appolinario was publicly available in 2004 and thus qualifies as prior art to
`
`the '813 patent under 35 U.S.C. § 102(b ). It does not appear to have been
`
`considered during prosecution of the '813 patent.
`
`2. Mickle (Ex.1023)
`
`Mickle was filed on April 10, 2006 and published on February 22, 2007.
`
`The application as filed qualifies as prior art to the '813 patent under 35 U.S.C.
`
`§ 102(e) and the publication qualifies as prior art under both§§ 102(a) and (e).
`
`Mickle does not appear to have been considered during prosecution of the '813
`
`patent. However, during prosecution the Examiner relied on Mickle 2005 and U.S.
`
`7 ,678, 770, which both claim priority to a common provisional
`
`application as Mickle.
`
`Marrazzi (Ex .. 1024)
`
`Marrazzi was publicly available in 1995 and thus qualifies as prior art to the
`
`'813 patent
`
`§ 102(b ). Marrazzi does not appear to
`
`been
`
`considered during prosecution of the '813 patent.
`
`Grilo (Ex .. 1025)
`
`Grilo was publicly
`
`qualifies as
`
`art
`
`to the 813 patent under 3 5
`
`does not appear to have
`
`1
`
`
`
`5.
`
`Ong (Ex.1017)
`
`Ong was published in 1983 and thus qualifies as prior art to the '813 patent
`
`under 35 U.S.C. § 102(b). Ong was before the USPTO during prosecution of the
`
`'813 patent but was not relied on for a rejection.
`
`6.
`
`DSM-IV-TR (Ex.1010)
`
`DSM-IV-TR was published in 2000 and thus qualifies as prior art to the '813
`
`patent under 35 U.S.C. § 102(b). DSM-IV-TR was before the USPTO during
`
`prosecution of the '813 patent but was not relied on for a rejection.
`
`7.
`
`Dukarm (Ex.1019)
`
`Dukarm was publically available in 2005 and thus qualifies as prior art to the
`
`'813 patent under 35 U.S.C. § 102(b). Dukarm was relied on
`
`a rejection during
`
`prosecution of the '813 patent, after which Applicant amended the claims and set
`
`forth counterarguments. (See supra Section V.B). The Examiner then withdrew
`
`the rejection.
`
`details of the relevant positions of Applicant and the Examiner
`
`with respect to Dukarm are discussed and analyzed below. (See infra Section X).
`
`Unpatentable
`Ground l.. Claims 1
`Under
`§ 103(a) over Appolinario in View of Mickle
`
`L
`
`Appolinario Teaches that Centrally Acting Anti-Obesity
`Agents Can
`to Treat BED
`According to
`DSM-IV-TR
`
`as
`
`of
`
`1 ).
`
`13
`
`
`
`according to such criteria. (Id. at 4 ). Although claim 1 of the '813 patent refers to
`
`DSM-IV-TR, which is a text revision of DSM-IV, the diagnostic features and
`
`research criteria for BED are the same in both. (Compare Ex.1026, DSM-IV,
`
`pp.9-11 with Ex.1010, DSM-IV-TR, pp.16-18; see also Ex.1009, Brewerton Dec.,
`
`ii 35). Thus, a POSA would have understood that Appolinario discloses
`
`diagnosing BED as defined in DSM-IV-TR. (See Ex.1009, Brewerton Dec. ii 78,
`
`n.1).
`
`Appolinario also describes three classes of drugs that have been studied in
`
`humans for the treatment of BED, one such class being anti-obesity agents. (See
`
`Ex.1020, Appolinario, p.1, Abstract). In particular, two anti-obesity agents that
`
`were successfully used
`
`the treatment of BED were identified:
`
`and sibutramine. (Id. at 3). Regarding d-fenfluramine, it "was found to promote
`
`binge eating suppression in
`
`patients
`
`and obesity," which
`
`high rate of remission (i.e., 80%) of binge eating. (Id.). For sibutramine, in a
`
`randomized controlled trial (RCT) sibutramine was found to improve binge eating
`
`frequency, reduce body weight, and decrease depressive symptoms. (Id.).
`
`52%
`
`rate of remission
`
`was reported. (See id. at 5).
`
`After
`
`would have "r<JP<HT11'"1'
`
`to ,,,,,,...,...,-,.,.,,,.., ......
`
`act on
`
`nervous
`
`by impacting
`
`14
`
`
`
`hunger and satiety (see supra Section VI; see also Ex.1009, Brewerton Dec. ilil 57-
`
`58), a POSA would have reasonably expected other centrally acting anti-obesity
`
`agents to be useful in the treatment of BED. (See Ex.1009, Brewerton Dec. il 80).
`
`Therefore, from Appolinario, a POSA would have learned to diagnose a patient
`
`with BED as defined in DSM-IV-TR and administer a centrally acting anti-obesity
`
`agent to the patient to treat BED. (See id.).
`
`Notwithstanding the positive results of d-fenfluramine and sibutramine, a
`
`POSA also would have been aware of their limitations. As noted in Appolinario,
`
`d-fenfluramine was withdrawn from the market due to cardiopulmonary risks.
`
`(Ex.1020, Appolinario, p.3). In the sibutramine RCT, while the sibutramine cohort
`
`had a 52% remission from binge eating, the placebo group had a 32% remission.
`
`(Id. at 5). Therefore, the net difference in the percentage of patients with remission
`
`from binge eating at the end of the trial was only 20%. (Id.; see also
`
`1009,
`
`Brewerton Dec. il 81 ).
`
`a
`
`would have been motivated to identify another centrally
`
`acting anti-obesity agent with positive properties for the treatment of BED.
`
`1009, Brewerton
`
`il 82).
`
`Acting
`
`the .,....,.a..-a.,., .. art
`
`Mickle,
`
`15
`
`
`
`[0098]). Following oral administration ofLDX dimesylate, d-amphetamine-a
`
`central nervous system stimulant-is released. (See e.g., id. ilil [0003], [0085],
`
`[0096], [0358]). Mickle also teaches methods for treating a patient by
`
`administering a therapeutically effective amount of an amphetamine prodrug, e.g.,
`
`LDX dimesylate, that is sufficient to prevent, ameliorate, and/or eliminate the
`
`symptoms of a disease. (See id. il [0124]). In particular, Mickle lists obesity as a
`
`preferred indication for treatment with the am
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