Petition for Inter Partes Review of USPN 8,618,135
`
`
`Filed on behalf of Coalition for Affordable Drugs VIII, LLC
`By: Dr. Gregory Gonsalves
`Reg. No. 43,639
`2216 Beacon Lane
`Falls Church, Virginia 22043
`(571) 419-7252
`gonsalves@gonsalveslawfirm.com
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`COALITION FOR AFFORDABLE DRUGS VIII, LLC, Petitioner
`
`v.
`
`TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA,
`Patent Owner, based on Electronic Records of PTO
`U.S. Patent 8,618,135 to Rader
`Filing Date: March 11, 2011
`Issue Date: December 31, 2013
`TITLE: METHODS FOR TREATING DISORDERS OR DISEASES ASSOCIATED WITH
`HYPERLIPIDEMIA AND HYPERCHOLESTEROLEMIA WHILE MINIMIZING SIDE EFFECTS
`
`IPR Trial No. TBD
`
`Petition for Inter Partes Review of U.S. Patent No. 8,618,135
`
`
`
`
`
`
`
`
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
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`
`
`
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`TABLE OF CONTENTS
`
`I.
`
`MANDATORY NOTICES UNDER 37 C.F.R. § 42.8. .................................. 1
`
`A.
`
`Real Party-in-Interest (37 C.F.R. § 42.8(B)(1)). ................................... 1
`
`B.
`
`C.
`
`Related Matters (37 C.F.R. § 42.8(b)(2)). ............................................. 3
`
`Notice of Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)). .......... 3
`
`D.
`
`Service Information under 37 C.F.R. § 42.8(b)(4). ............................... 3
`
`E.
`
`Service on Patent Owner Under 37 C.F.R. §§ 42.106(a) and
`42.105(a). ............................................................................................... 3
`
`II.
`
`GROUNDS FOR STANDING UNDER 37 C.F.R. § 42.104(A). .................. 4
`
`III.
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(B)). ................. 4
`
`IV.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT. ............................. 5
`
`V.
`
`THE ‘135 PATENT PRIORITY DATE IS MARCH 7, 2005; THE
`‘915 PROVISIONAL DOES NOT SUPPORT THE ISSUED
`CLAIMS. ......................................................................................................... 8
`
`A. No Support for the Full Scope of the Claimed Dose Ranges. .............. 8
`
`B.
`
`In Addition, No Support for “the Piperidine N-oxide Thereof”. ........10
`
`VI. SCOPE AND CONTENT OF THE PRIOR ART. ........................................12
`
`Elevated Serum Cholesterol and Lipid Levels Were Recognized
`Risk Factors For Cardiovascular Disease. ..........................................12
`
`Known Drug Classes and Dosing Regimens Pre-March 2003. ..........12
`
`The Content of the MTP Inhibitor Art Pre-March 2004. ....................15
`
`1.
`
`2.
`
`Pink Sheet 2004 is Prior Art. ....................................................15
`
`Stein’s 2004 Presentation – Published Before March 5,
`2004 and Again by At Least April 15, 2004 – is Prior
`Art. ............................................................................................16
`
`i
`
`A.
`
`B.
`
`C.
`
`
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`3.
`
`The Prior Art Taught Step-Wise MTP Inhibitor Dosing
`Over Seven Levels; the Rationale; and Expected
`Efficacy. ....................................................................................22
`
`VII. U.S. PATENT NO. 8,618,135 AND ITS FILE HISTORY. .........................24
`
`A.
`
`B.
`
`C.
`
`The ‘135 Patent Repeats Information Already Known to
`Ordinarily-Skilled Artisans. ................................................................24
`
`The ‘135 Patent File History. ..............................................................26
`
`The European Opposition Proceedings. ..............................................28
`
`VIII. THE LEVEL OF ORDINARY SKILL IN THE ART. .................................28
`
`IX. CLAIM CONSTRUCTION STATEMENT (37 C.F.R.
`§ 42.104(B)(3)). .............................................................................................29
`
`X.
`
`EXPLANATION OF GROUNDS FOR UNPATENTABILITY. ................30
`
`A. Ground I: Obviousness Over Pink Sheet 2004 in View of
`Chang. ..................................................................................................31
`
`1.
`
`The Claimed Lomitapide Escalating-Dosing Approach
`was Already Taught for Implitapide. ........................................32
`
`2. Motivation to Combine Pink Sheet 2004 with Chang. .............39
`
`3.
`
`Reasonable Expectation of Success With Lomitapide. ............43
`
`B.
`
`Ground II: Obviousness Over Stein 2004 in View of Chang. ............46
`
`1.
`
`There Are No Non-Obvious Differences. .................................46
`
`2. Motivation to Combine Stein 2004 with Chang. ......................53
`
`3.
`
`Reasonable Expectation of Success With Lomitapide. ............55
`
`C.
`
`Secondary Considerations Presented During Prosecution Do
`Not Rebut the Prima Facie Case of Unpatentability. .........................56
`
`XI. CONCLUSION. .............................................................................................60
`
`
`
`
`ii
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`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`EXHIBIT LIST PURSUANT TO 37 C.F.R. § 42.63(e) AND
`TABLE OF ABBREVIATIONS
`
`
`
`iii
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`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`Ex. No.
`
`Description
`
`1001
`
`Certified U.S. Patent No. 8,618,135 to Rader.
`
`1002
`
`Declaration of Randall M. Zusman, M.D.
`
`1003
`
`Declaration of Michael Mayersohn, Ph.D.
`
`1004
`
`Affidavit of Christopher Butler, Office Manager, Internet Archive,
`authenticating Internet Archive URLs (June 16, 2015) (attaching as
`Ex. A:
`
`PPD News & IR Presentations (2004/04/15) (available at
`https://web.archive.org/web/20040415065142/http://ppdi.com/PPD_6
`_12.htm)).
`
`1005
`
`Affidavit of Christopher Butler, Office Manager, Internet Archive,
`authenticating Internet Archive URLs (June 12, 2015) (attaching as
`Ex. A:
`
`PPD News Releases(2004/02/13) (available at
`https://web.archive.org/web/20040213233245/http://www.ppdi.com/P
`PD_U6.htm?ID=126662);
`
`PPD News & IR Presentations(2003/12/12) (available at
`https://web.archive.org/web/20031212193444/http://ppdi.com/PPD_6
`_12.htm);
`
`PPD News & IR Presentations (2004/06/04) (available at
`https://web.archive.org/web/20040604203252/http://www.ppdi.com/P
`PD_6_12.htm)).
`
`1006
`
`Certified U.S. Provisional Patent Application No. 60/550,915.
`
`1007
`
`U.S. Patent No. 8,618,135 (highlighting dosing information not
`present in U.S. Provisional Patent Application No. 60/550,915).
`
`1008
`
`U.S. Patent Application No. 13/046,118.
`
`1009
`
`In re Application of: Rader, U.S. Patent Application No. 13/046,118,
`Amendment and Response to Oct. 2, 2012 Office Action (Mar. 4,
`2013).
`
`
`
`iv
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`In re Application of: Rader, U.S. Patent Application No. 13/046,118,
`Declaration of William Sasiela, Ph.D. (Apr. 8, 2010).
`
`In re Application of: Rader, U.S. Patent Application No. 13/046,118,
`Notice of Allowance (May 10, 2013).
`
`In re Application of: Rader, U.S. Patent Application No13/046,118,
`Notice of Allowance (Sept. 3, 2013).
`
`Bayer/PPD Implitapide Development Follows Zetia Model As Statin
`Add-On, 66 THE PINK SHEET 17 (Feb. 16, 2004).
`
`Evan Stein, CEO & President, MRL Int’l (Division of PPD),
`Presentation Given at PPD’s Analyst Day, Microsomal Triglygeride
`[sic] Transfer Protein (MTP) Inhibitor (implitapide) program (Feb. 5,
`2004).
`
`George Chang et al., Microsomal triglyceride transfer protein (MTP)
`inhibitors: Discovery of clinically active inhibitors using high-
`throughput screening and parallel synthesis paradigms, 5 CURRENT
`OPINION IN DRUG DISCOVERY & DEV. 562 (2002).
`
`Charles E. Chandler et al., CP-346086: an MTP inhibitor that lowers
`plasma cholesterol and triglycerides in experimental animals and in
`humans, 44 J. OF LIPID RES. 1887 (2003).
`
`FDA approves Zetia -- first new class to treat cholesterol since statins
`introduced, DRUGS.COM (Oct. 28, 2002),
`http://www.drugs.com/news/fda-approves-zetia-first-new-class-
`cholesterol-since-statins-introduced-3164.html (last visited July 22,
`2015).
`
`1018
`
`John R. Wetterau et al., An MTP Inhibitor That Normalizes
`Atherogenic Lipoprotein Levels in WHHL Rabbits, 282 SCI. 751
`(1998).
`
`1019
`
`U.S. Patent No. 5,712,279 to Biller et al.
`
`1020
`
`Evan Stein, OPPOSITION AGAINST EUROPEAN PATENT NO. 1 725 234
`B9 (filed Aug. 21, 2013).
`
`
`
`v
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`THOMPSON PDR, PHYSICIANS’ DESK REFERENCE 506-09, 1101-06,
`1813-21, 2036-41, 2126-31, 2547-51, 2729-31, 2865-68 (57th ed.
`2003) (excerpting product information for Tricor®, Pravachol®,
`Advicor®, Niaspan®, Mevacor®, Zocor®, Lipitor®, Colestid®, and
`Lescol®).
`
`THOMPSON PDR, PHYSICIANS’ DESK REFERENCE 2118-23, 3085-89
`(58th ed. 2004) (excerpting product information for Zetia®).
`
`U.S. FOOD & DRUG ASS’N, ESTIMATING THE MAXIMUM SAFE
`STARTING DOSE IN INITIAL CLINICAL TRIALS FOR THERAPEUTICS IN
`ADULT HEALTHY VOLUNTEERS: GUIDANCE FOR INDUSTRY (2005).
`
`Prices and coupons for 30 capsules of Juxtapid 5mg, 10mg, 20mg,
`30mg, 40mg and 60mg (brand), GOODRX.COM,
`http://www.goodrx.com/juxtapid (last visited July 16, 2015).
`
`Dan Mangan, ‘Fast Money’ faux pas: Firm draws FDA warning, DOJ
`subpoena, CNBC.COM (Jan. 13, 2014),
`http://www.cnbc.com/id/101327742 (last visited July 22, 2015).
`
`1026 Malcolm Rowland & Thomas N. Tozer, CLINICAL
`PHARMACOKINETICS: CONCEPTS AND APPLICATIONS 57 (3d ed. 1995).
`
`1027
`
`Curriculum Vitae of Randall M. Zusman, M.D.
`
`1028
`
`Documents considered by Randall M. Zusman, M.D.
`
`1029
`
`Curriculum Vitae of Michael Mayersohn, Ph.D.
`
`1030
`
`Documents considered by Michael Mayersohn, Ph.D.
`
`1031
`
`Third Report of the National Cholesterol Education Program (NCEP)
`Expert Panel on Detection, Evaluation and Treatment of High Blood
`Cholesterol in Adults (Adult Treatment Panel III) Final Report, 106
`CIRCULATION 3143 (2002).
`
`1032 Michael Mayersohn, Principles and Applications of
`Pharmacokinetics, in MEDICAL TOXICOLOGY 282 (Richard C. Dart
`ed., 3d ed. 2004).
`
`
`
`vi
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`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`1033 Masashi Shiomi & Takashi Ito, MTP inhibitor decreases plasma
`cholesterol levels in LDL receptor-deficient WHHL rabbits by
`lowering the VLDL secretion, 431 EUR. J. OF PHARMACOLOGY 127
`(2001).
`
`1034
`
`Declaration of Jeffery A. Marx.
`
`1035
`
`1036
`
`Press Release, Cigna Corp., Cigna Announces Appearance at CIBC
`Healthcare Conference (Nov. 7, 2003),
`http://newsroom.cigna.com/article_display.cfm?article_id=236.
`
`Press Release, Gilead Scis., Gilead Sciences to Present at the 7th
`Annual Lehman Brothers Global Healthcare Conference on Friday,
`March 5th; Webcast Available Through Gilead Corporate Website
`(Mar. 4, 2004),
`http://gilead.com/news/press-releases/2004/3/gilead-sciences-to-
`present-at-the-7th-annual-lehman-brothers-global-healthcare-
`conference-on-friday-march-5th-webcast-available-through-gilead-
`corporate-website?mode=print.
`
`1037
`
`Press Release, PR Newswire, Dot Hill to Present at Robert W. Baird
`2004 Growth Stock Conference (May 4, 2004),
`http://www.prnewswire.com/news-releases/dot-hill-to-present-at-
`robert-w-baird-2004-growth-stock-conference-73777807.html.
`
`1038 Margaret A. McDowell et al., Anthropometric Reference Data for
`Children and Adults: U.S. Population, 1999-2002, CDC ADVANCE
`DATA FROM VITAL & HEALTH STATS. NO. 361 (2005).
`
`1039
`
`1040
`
`1041
`
`
`
`In re Application of: Rader, U.S. Patent Application No. 13/046,118,
`Amendment (Sept. 25, 2013).
`
`In re Application of: Rader, U.S. Patent Application No. 13/046,118,
`Supplemental Information Disclosure Statement (Sept. 25, 2013).
`
`In re Application of: Rader, U.S. Patent Application No. 13/046,118,
`Notice of Allowance (Oct. 29, 2013).
`
`vii
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`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`TABLE OF ABBREVIATIONS
`
`Abbreviation
`
`‘915
`Provisional
`
`Definition
`
`U.S. Provisional Patent Application No. 60/550,915
`
`‘268 patent U.S. Patent No. 7,932,268
`
`‘923
`application
`
`U.S. Patent Application No. 10/591,923 (issued as ‘268 patent)
`
`‘135 patent U.S. Patent No. 8,618,135
`
`‘118
`application
`
`U.S. Patent Application No. 13/046,118 (issued as ‘135 patent)
`
`ApoB
`
`Apolipoprotein B
`
`CFAD
`
`Coalition For Affordable Drugs VIII, LLC
`
`Credes
`
`Hayman Credes Master Fund, L.P.
`
`HCM
`
`Hayman Capital Management, L.P.
`
`HCMF
`
`Hayman Capital Master Fund, L.P.
`
`HDL
`
`High density lipoprotein
`
`HeFH
`
`Heterozygous familial hypercholesterolemia
`
`HI
`
`Hayman Investments, L.L.C.
`
`HOF
`
`Hayman Orange Fund SPC – Portfolio A
`
`HoFH
`
`Homozygous familial hypercholesterolemia
`
`HOM
`
`Hayman Offshore Management, Inc.
`
`IDL
`
`Intermediate-density lipoprotein
`
`LDL
`
`Low density lipoprotein
`
`viii
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`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`Abbreviation
`
`Definition
`
`LDL-C
`
`Low density lipoprotein cholesterol
`
`Lp(a)
`
`Lipoprotein (a)
`
`Mayersohn
`
`Declaration of Michael Mayersohn, Ph.D. in Support of
`Coalition for Affordable Drug’s Petition for Inter Partes Review
`of U.S. Patent No. 8,618,135
`
`MTP
`
`Microsomal triglyceride transfer proteins
`
`TG
`
`Triglycerides
`
`Total-C
`
`Total cholesterol
`
`VLDL
`
`Very low density lipoprotein
`
`WHHL
`
`Watanabe-heritable hyperlipidemic
`
`Zusman
`
`Declaration of Randall M. Zusman, M.D. in Support of Coalition
`for Affordable Drug’s Petition for Inter Partes Review of U.S.
`Patent No. 8,618,135
`
`
`
`ix
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`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`TABLE OF AUTHORITIES
`
`
`
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`
`
` PAGES
`
`Federal Cases
`
`Allergan v. Sandoz,
`726 F.3d 1286 (Fed. Cir. 2013) ............................................................................56
`
`Alza Corp. v. Mylan Labs., Inc.,
`464 F.3d 1286 (Fed. Cir. 2006) ............................................................................44
`
`Bayer Healthcare Pharms. Inc. v. Watson Pharms. Inc.,
`713 F.3d 1369 (Fed. Cir. 2013) ......................................................... 39, 40, 41, 44
`
`Carnegie Mellon Univ. v. Hoffman-La Roche, Inc.,
`541 F.3d 1115 (Fed. Cir. 2008) ............................................................................10
`
`Ex parte Zeying Ma & Yubai Bi,
`Appeal 2013-001589, 2014 WL 1005343 (P.T.A.B. January 27, 2014) .............10
`
`Galderma Laboratories, L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ....................................................................... 38, 52
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) .............................................................................................5, 56
`
`Hoffman-LaRoche, Inc. v. Apotex, Inc.,
`748 F.3d 1326 (Fed. Cir. 2013) ............................................................................59
`
`In re Dillon,
`919 F.2d 688 (Fed Cir. 1990) ...............................................................................56
`
`In re Hall,
`781 F.2d 897 (Fed. Cir. 1986) ....................................................................... 20, 22
`
`In re Klopfenstein,
`380 F.3d 1345 (Fed. Cir. 2004) ..................................................................... 17, 18
`
`In re Vaeck,
`947 F.2d 488 (Fed. Cir. 1991) ..............................................................................10
`
`x
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`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 40, 41
`
`Lockwood v. Am. Airlines, Inc.,
`107 F.3d 1565 (Fed. Cir. 1997) .............................................................................. 8
`
`McNeil-PPC, Inc. v. L. Perrigo Co.,
`337 F.3d 1362 (Fed. Cir. 2003) ............................................................................44
`
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) ............................................................................43
`
`Merck & Co., Inc. v. Teva Pharms., USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005) ..................................................................... 42, 60
`
`Muniauction, Inc. v. Thomson Corp.,
`32 F.3d 1318 (Fed. Cir. 2008) ..............................................................................57
`
`Novozymes A/S v. Dupont Nutrition Biosciences APS,
`723 F.3d 1336 (Fed. Cir. 2013) ............................................................................11
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) ............................................................................57
`
`Orthopedic Equip. Co. v. United States,
`702 F.2d 1005 (Fed. Cir. 1983) ............................................................................60
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ............................................................................56
`
`Purdue Pharma, L.P. v. Faulding, Inc.,
`230 F.3d 1320 (Fed. Cir. 2000) ............................................................................10
`
`Santarus, Inc. v. Par Pharm., Inc.,
`694 F.3d 1344 (Fed. Cir. 2012) ............................................................................45
`
`Senju Pharm. Co. v. Lupin Ltd.,
`780 F.3d 1337 (Fed. Cir. 2015) ..................................................................... 42, 57
`
`Suffolk Techs., LLC v. AOL Inc.,
`752 F.3d 1358 (Fed. Cir. 2014) ............................................................................20
`
`xi
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`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`Trading Techs. Int’l Inc. v. eSpeed, Inc.,
`595 F.3d 1340 (Fed. Cir. 2010) ..........................................................................8, 9
`
`Tyco Healthcare Grp. LP v. Mut. Pharm. Co.,
`642 F.3d 1370 (Fed. Cir. 2011) ............................................................................32
`
`Voter Verified, Inc. v. Premier Election Solutions, Inc.,
`698 F.3d 1374 (Fed. Cir. 2012) ..................................................................... 17, 20
`
`Wyers v. Master Lock Co.,
`616 F.3d 1231 (Fed. Cir. 2010) ..................................................................... 56, 57
`
`Federal Statutes
`
`35 U.S.C. § 102 ........................................................................................................17
`
`35 U.S.C. § 102(a) ........................................................................................... passim
`
`35 U.S.C. § 102(b) ........................................................................................... passim
`
`35 U.S.C. § 312 .......................................................................................................... 1
`
`35 U.S.C. § 314(a) ...................................................................................................31
`
`Federal Regulations
`
`21 C.F.R. § 50.25 (2001) .........................................................................................59
`
`37 C.F.R. § 42.10(b) .................................................................................................. 1
`
`37 C.F.R. § 42.100(b) ..............................................................................................29
`
`37 C.F.R. § 42.108 ..................................................................................................... 1
`
`37 C.F.R. § 42.15(a) ................................................................................................... 1
`
`37 C.F.R. § 42.22(A).................................................................................................. 8
`
`37 C.F.R. § 42.63(e) ................................................................................................... 1
`
`37 C.F.R. § 42.8(a)(1) ................................................................................................ 1
`
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 1
`
`xii
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`Petition for Inter Partes Review of USPN 8,618,135
`
`
`45 C.F.R. § 46.116 (2001) .......................................................................................59
`
`xiii
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`Coalition For Affordable Drugs VIII LLC (“CFAD” or “Petitioner”) requests
`
`inter partes review (35 U.S.C. § 312 and 37 C.F.R. § 42.108) seeking cancellation
`
`of Claims 1-10 of U.S. Patent No. 8,618,135 (“the ‘135 patent”) (Exhibit (“CFAD
`
`Ex.”) 1001) issued December 31, 2013 to Daniel J. Rader. A Power of Attorney (37
`
`C.F.R. § 42.10(b)) and an Exhibit List (37 C.F.R. § 42.63(e)), are concurrently-filed.
`
`Please charge the required $23,000 fee (37 C.F.R. § 42.15(a)) to Deposit Acct. No.
`
`50-3626 (Customer ID No. 60024). The Office is authorized to charge any fee
`
`deficiencies and credit any overpayments to Deposit Acct. No. 50-3626 (Customer
`
`ID No. 60024).
`
`I. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8.
`
`Petitioner provides the following mandatory notices under 37 C.F.R.
`
`§§ 42.8(a)(1) and 42.8(b).
`
`A. Real Party-in-Interest (37 C.F.R. § 42.8(B)(1)).
`
`Pursuant to 37 C.F.R. § 42.8(b)(1), Petitioner certifies that Coalition For
`
`Affordable Drugs VIII LLC, Hayman Credes Master Fund, L.P. (“Credes”),
`
`Hayman Orange Fund SPC – Portfolio A (“HOF”), Hayman Capital Master Fund,
`
`L.P. (“HCMF”), Hayman Capital Management, L.P. (“HCM”), Hayman Offshore
`
`Management, Inc. (“HOM”), Hayman Investments, L.L.C. (“HI”), J. Kyle Bass, and
`
`Erich Spangenberg are the real parties in interest (collectively “RPI”). The RPI
`
`hereby certify the following information: CFAD VIII is a wholly owned subsidiary
`
`
`
`1
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`of Credes. Credes is a limited partnership. HOF is a segregated portfolio company.
`
`HCMF is a limited partnership. HCM is the general partner and investment manager
`
`of Credes and HCMF. HCM is the investment manager of HOF. HOM is the
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`administrative general partner of Credes and HCMF. HI is the general partner of
`
`HCM. J. Kyle Bass is the sole member of HI and the sole shareholder of HOM.
`
`CFAD VIII, Credes, HOF and HCMF act, directly or indirectly, through HCM as
`
`the general partner and/or investment manager of Credes, HOF and HCMF. nXnP
`
`is a paid consultant to HCM. Erich Spangenberg is the Manager and majority
`
`member of nXnP. IPNav is a paid consultant to nXnP. Erich Spangenberg is the
`
`Manager and majority member of IPNav. Other than J. Kyle Bass in his capacity of
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`the Chief Investment Officer of HCM, and nXnP and Erich Spangenberg in his
`
`capacity as the Manager/CEO of nXnP, no other person (including any investor,
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`limited partner, or member or any other person in any of CFAD VIII, Credes, HOF,
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`HCMF, HCM, HOM, HI, nXnP or IPNav) has authority to direct or control (i) the
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`timing of, filing of, content of, or any decisions or other activities relating to this
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`petition or (ii) any timing, future filings, content of, or any decisions or other
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`activities relating to the future proceedings related to this Petition. All of the costs
`
`associated with this petition will be borne by HCM, CFAD VIII, Credes, HOF and/or
`
`HCM.
`
`
`
`2
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`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2)).
`
`Petitioner is concurrently filing a Petition for Inter Partes Review of U.S.
`
`Patent No. 7,932,268, which is a member of the same family as the ‘135 patent.
`
`C. Notice of Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)).
`
` Lead Counsel
`Dr. Gregory Gonsalves
`Reg. No. 43,639
`2216 Beacon Lane
`Falls Church, Virginia 22043
`(571) 419-7252
`gonsalves@gonsalveslawfirm.com
`
` Back-Up Counsel
`Christopher Casieri
`Reg. No. 50,919
`MCNEELY, HARE & WAR, LLP
`12 Roszel Road, Suite C104
`Princeton, NJ 08540
`Phone: (609) 731-3668
`Fax: (202) 478-1813
`chris@miplaw.com
`
`
`
`D.
`
`Service Information under 37 C.F.R. § 42.8(b)(4).
`
`Please address all correspondence to the Lead Counsel at the above address.
`
`Petitioner
`
`consents
`
`to
`
`electronic
`
`service
`
`by
`
`email
`
`to:
`
`gonsalves@gonsalveslawfirm.com and chris@miplaw.com.
`
`E.
`
`Service on Patent Owner Under 37 C.F.R. §§ 42.106(a) and
`42.105(a).
`
`This petition is being served by Express Mail on The Trustees of the
`
`University of Pennsylvania, owners of the ‘135 patent, at their address of record
`
`according to the USPTO PAIR database: The Trustees of the University of
`
`Pennsylvania, 3160 Chestnut Street Suite 200, Center for Technology Transfer,
`
`Philadelphia, PA 19104-6283.
`
`
`
`3
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`II. GROUNDS FOR STANDING UNDER 37 C.F.R. § 42.104(A).
`
`Petitioner certifies that the ‘135 patent is available for inter partes review, and
`
`that Petitioner is not barred or estopped from requesting an inter partes review
`
`challenging the patent claims on the grounds identified in this Petition. No RPI has
`
`filed a civil action challenging the validity of the ‘135 patent, nor has any RPI been
`
`served with a complaint alleging infringement of the ‘135 patent more than one year
`
`prior to the filing of this Petition.
`
`The public interest requires ensuring monopoly privileges are not granted by
`
`an invalid patent, particularly because Juxtapid® sells for more than $900.00 per pill,
`
`and costs nearly $330,000 per patient per year. (See CFAD Ex. 1024; CFAD Ex.
`
`1025). Patentee and its licensee, Aegerion Pharmaceuticals, Inc., have secured such
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`pricing through FDA regulatory exclusivity and BMS’s lomitapide molecule
`
`patents, but cannot extend it with the obvious ‘135 patent.
`
`III.
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)).
`
`Petitioner respectfully requests inter partes review and cancellation of claims
`
`1-10 of the ‘135 patent based on the grounds set forth in the table below:
`
`Ground Challenged
`Claims
`1-10
`1-10
`
`1
`2
`
`Statutory
`Basis
`§ 103
`§ 103
`
`References
`
`Pink Sheet 2004 in view of Chang
`Stein 2004 in view of Chang
`
`Sections IV-X below explain how the ‘135 patent claims—properly
`
`construed—are unpatentable on the grounds listed above. See Graham v. John
`
`
`
`4
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`Deere Co., 383 U.S. 1, 17-18 (1966) (reciting four-factor obviousness test).
`
`In support of these grounds for unpatentability, Petitioner submits the expert
`
`declaration of Randall M. Zusman, M.D. to discuss the relevant field and art in
`
`general, and the factual and opinion bases for each of the Graham factors underlying
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`Petitioner’s Grounds 1 and 2. (CFAD Ex. 1002). Petitioner also submits the
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`declaration of pharmacokinetics expert Michael Mayersohn, Ph.D., on the specific
`
`dosing-related teachings. (CFAD Ex. 1003). Petitioner further relies on the Exhibits
`
`set forth on the concurrently filed Exhibit List, including the Pink Sheet 2004 (CFAD
`
`Ex. 1013), Stein 2004 (CFAD Ex. 1014), and Chang (CFAD Ex. 1015) references.
`
`Pink Sheet 2004 and Stein 2004 publications were not before the examiner during
`
`the substantive prosecution of the application leading to the ‘135 patent; patentee
`
`submitted those references in September 2013 only after receiving a second Notice
`
`of Allowance. Chang was cited but never substantively discussed.
`
`IV.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT.
`
`The ‘135 patent claims are invalid. They merely claim methods of using a
`
`known drug, to treat known medical conditions, for which the drug was known to be
`
`effective, with known dose-titration methods disclosed in the prior art.
`
`The ‘135 patent issued on December 31, 2013 from Application No.
`
`13/046,118 (the ‘118 Application) filed March 11, 2011, itself a continuation of
`
`
`
`5
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`Application No. 10/591,923 (the ‘923 Application) filed March 7, 2005.1 The patent
`
`recognizes hyperlipidemia and hypercholesterolemia are characterized by elevated
`
`serum levels of cholesterol (total and LDL-C) and lipids (e.g., triglycerides (TG)),
`
`which increase the risk of cardiovascular disease. (CFAD Ex. 1001, col. 1:24 – col.
`
`2:3). The ‘135 patent characterizes as inventive treating hyperlipidemia or
`
`hypercholesterolemia with drugs that inhibit microsomal triglyceride transfer
`
`proteins (“MTP”), i.e., MTP inhibitors, by applying step-wise escalating dosing
`
`regimens. (See id. at col. 7:11-24; col. 11:60 – col. 13:23).
`
`Administering anti-cholesterol drugs in step-wise escalating doses was
`
`standard practice with, e.g., statins, fibrates, and niacin. (CFAD Ex. 1002
`
`(“Zusman”) ¶¶ 37-38, 40, 43-47). Dr. Evan Stein specifically taught applying step-
`
`wise escalating dosing to the MTP inhibitor implitapide to treat hyperlipidemia and
`
`hypercholesterolemia—facts published before the relevant filing date. (See CFAD
`
`Ex. 1013; CFAD Ex. 1014). Dr. Stein also disclosed the rationales for this dosing
`
`approach: minimizing side effects, rendering MTP inhibitors marketable as adjunct
`
`therapy to statins; and treating patients not effectively treated by statins. (Zusman,
`
`¶¶ 69-70, 103-04; CFAD Ex. 1003 (“Mayersohn”) ¶¶ 57, 59-60).
`
`
`1 Patentee cannot claim priority to its March 5, 2004 provisional application given
`
`the elements of the issued claims of the ‘135 patent. (See Section V, below).
`
`
`
`6
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`The ‘135 patent’s named inventor, Dr. Rader, was a clinical investigator on
`
`the September 2003 implitapide studies Dr. Stein designed and led. (CFAD
`
`Ex. 1020:8). Dr. Rader filed his provisional application in March 2004. But before
`
`then, two February 2004 publications (one by Dr. Stein and another by The Pink
`
`Sheet) had already disclosed Dr. Stein’s implitapide step-wise escalating dosing.
`
`(See Section IX, below). Yet Dr. Rader initially claimed he invented step-wise
`
`dosing for all MTP inhibitors. (See CFAD Ex. 1008:28-31). As issued, the ‘135
`
`patent claims merely apply Dr. Stein’s step-wise escalating dosing approach to the
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`MTP inhibitor lomitapide. (See CFAD Ex. 1001, col. 19:42-67 (claim 1)).
`
`The ordinarily-skilled artisan required no great leap to apply Dr. Stein’s
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`implitapide dosing regimen to other MTP inhibitors such as lomitapide. (Zusman,
`
`¶ 33; Mayersohn, ¶ 27). Lomitapide was a known, potent MTP inhibitor. (See
`
`CFAD Ex. 1001, col. 5:47–col. 6:19; Zusman, ¶ 24). The prior art taught
`
`lomitapide’s efficacy in vitro, in animal models, and in humans, and also taught
`
`lomitapide had clinical effects similar to implitapide. (Zusman, ¶¶ 62-63, 96-99;
`
`Mayersohn, ¶¶ 18-19; see also CFAD Ex. 1015:563-66).
`
` As detailed below, the published prior art disclosures and the skilled artisan’s
`
`motivation to apply step-wise escalating dosing regimens to MTP inhibitors
`
`(including lomitapide) with a reasonable expectation of success render independent
`
`claims 1, 9, and 10, and dependent claims 6-8 of the ‘135 patent obvious at the time
`
`
`
`7
`
`

`

`Petition for Inter Partes Review of USPN 8,618,135
`
`
`of filing. The additional elements found in dependent claims 2-5 merely reflect uses,
`
`targets, and results already known or inherent in the dosing method itself. (Zusman,
`
`¶¶ 150-165; CFAD Ex. 1015:562, 565-66).
`
`For the reasons set forth herein, under 37 C.F.R. § 42.22(A), Petitioner
`
`requests Inter Partes Review and cancellation of claims 1-10. Petitioner’s detailed
`
`statement of the reasons for the relief requested appears in Sections V-X below.
`
`V. THE ‘135 PATENT PRIORITY DATE IS MARCH 7, 2005; THE ‘915
`PROVISIONAL DOES NOT SUPPORT THE ISSUED CLAIMS.
`
`The ‘135 patent claims receive the benefit of U.S. Provisional Patent
`
`Application 60/550,915 (“the ‘915 Provisional”) only if that application “describe[s]
`
`an invention, and . . . in sufficient detail that one skilled in the art can clearly
`
`conclude that [Dr. Rader] invented the claimed invention as of the filing date
`
`sought,” such that he was “in possession of” the invention. See Lockwood v. Am.
`
`Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997); Trading Techs. Int’l Inc. v.
`
`eSpeed, Inc., 595 F.3d 1340, 1359 (Fed. Cir. 2010). The ‘915 Provisional does not
`
`support the claimed dose ranges or the piperidine N-oxide derivatives.
`
`A. No Support for the Full Scope of the Claimed Dose Ranges.
`
`Independent claim 1 recites a step-wise escalating dose method where the first
`
`dose ranges from “about 2 to about 13 mg/day”; the second “from about 5 to about
`
`30 mg/day” and the third “from about 10 to about 50 mg/day,” with dose escalation
`
`at “about 1 to about 5 weeks.” (CFAD Ex. 1001, col. 19:40–67). Independent claims
`
`
`
`8
`
`

`

`Petition for In