Paper No. ______
`Filed: May 18, 2016
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________
`
`DR. REDDY’S LABORATORIES, LTD. and
`DR. REDDY’S LABORATORIES, INC.,
`Petitioner
`
`v.
`
`HELSINN HEALTHCARE S.A.,
`Patent Owner
`
`______________________
`
`Case PGR2016-00008
`Patent 9,173,942
`
`______________________
`
`Patent Owner’s Preliminary Response
`to Petition for Post-Grant Review
`of U.S. Patent No. 9,173,942
`
`

`
`
`
`TABLE OF CONTENTS
`
`Case PGR2016-00008
`
`I.
`II.
`
`B.
`
`C.
`
`Introduction ..................................................................................................... 1
`Background ..................................................................................................... 5
`A. Aloxi® Is a Breakthrough Drug Product
`for Patients Suffering from CINV ........................................................ 5
`The Development of Aloxi® ................................................................. 7
`1.
`Roche’s Early Palonosetron Work ............................................. 7
`Patent Owner Resumes Roche’s
`2.
`Abandoned Palonosetron Program ............................................ 8
`Patent Owner’s Partnership with MGI ..................................... 10
`3.
`The ’942 Patent Discloses Stable Palonosetron
`Formulations for Treating Emesis ...................................................... 12
`The ’942 Patent Discloses Palonosetron
`1.
`Formulations for Treating Emesis ........................................... 12
`The ’942 Patent Discloses Stable,
`Low-Concentration Palonosetron Formulations ...................... 14
`Prosecution History of the ’942 Patent and Its Family Members ...... 16
`Related Litigations ............................................................................. 16
`1.
`The ANDA Action ................................................................... 17
`2.
`The 505(b)(2) Action ............................................................... 19
`3.
`The Second 505(b)(2) Action .................................................. 20
`III. DRL Has Failed to Show That the ’942 Patent
`Claims Lack Written Description Support ................................................... 20
`A.
`The Specification Discloses the Claimed Formulations,
`Including That They Are Stable and Effective .................................. 21
`B. DRL’s Arguments Miscomprehend the Claimed Inventions ............. 25
`C.
`The Cases Relied upon By DRL Are Inapposite ............................... 27
`D.
`The Fausel Declaration Cannot Support DRL’s Written
`Description Arguments ...................................................................... 30
`
`2.
`
`D.
`E.
`
`
`
`
`
`i
`
`

`
`Case PGR2016-00008
`
`TABLE OF CONTENTS
`
`IV. The Claimed Inventions Are Not Invalid
`under the On-Sale Bar Based on the MGI Agreement ................................. 33
`A. Under the Correct Interpretation of AIA § 102, the MGI
`Agreement Cannot Invalidate the ’942 Patent Claims ....................... 33
`Any Allegedly Invalidating Sale or Offer for Sale
`1.
`Must Have Made the Claimed Inventions
`Available to the Public ............................................................. 34
`a.
`The Plain Language Supports Patent Owner’s
`Statutory Interpretation .................................................. 35
`The Legislative History Supports the Patent
`Owner’s Statutory Interpretation ................................... 39
`The Policy Behind the AIA Supports Patent
`Owner’s Statutory Interpretation ................................... 44
`Patent Owner’s Interpretation Is Consistent
`with the Patent Office’s Interpretation .......................... 46
`The MGI Agreement Did Not Make the Claimed
`Formulations “Available to the Public” ................................... 48
`The MGI Agreement Was Not a Commercial
`Offer for Sale of the Claimed Inventions ........................................... 51
`The Claimed Inventions Were Not Ready for Patenting ................... 55
`The Board Should Exercise Its Discretion under
`35 U.S.C. § 325(d) and Not Adopt This Ground ............................... 60
`V. DRL’s Claim Constructions Are
`Unnecessary or Incorrect .............................................................................. 61
`VI. Conclusion .................................................................................................... 63
`
`2.
`
`B.
`
`C.
`D.
`
`b.
`
`c.
`
`d.
`
`ii
`
`

`
`TABLE OF AUTHORITIES
`
`Case PGR2016-00008
`
`
`
`Page(s)
`
`Cases
`3D Sys., Inc. v. Aarotech Labs., Inc.,
`160 F.3d 1373 (Fed. Cir. 1998) .......................................................................... 44
`
`Abuelhawa v. United States,
`556 U.S. 816 (2009) ............................................................................................ 38
`
`Alcon Research Ltd. v. Barr Labs., Inc.,
`745 F.3d 1180 (Fed. Cir. 2014) .......................................................................... 21
`
`Allergan, Inc. v. Sandoz Inc.,
`796 F.3d 1293 (Fed. Cir. 2015) .......................................................... 4, 20, 21, 25
`
`Anascape, Ltd. v. Nintendo of Am., Inc.,
`601 F.3d 1333 (Fed. Cir. 2010) .......................................................................... 29
`
`Bettcher Indus., Inc. v. Bunzl USA, Inc.,
`661 F.3d 629 (Fed. Cir. 2011) ............................................................................ 35
`
`Coal. for Affordable Drugs XI LLC v. Insys Pharma, Inc.,
`IPR2015-01799, Paper 9 (Mar. 10, 2016) .......................................................... 31
`
`Cooper Cameron v. Kvaerner Oilfield Products., Inc.,
`291 F.3d 1317 (Fed. Cir. 2002) .......................................................................... 28
`
`Crandon v. United States,
`494 U.S. 152 (1990) ............................................................................................ 44
`
`Dey, L.P. v. Sunovion Pharms., Inc.,
`715 F.3d 1351 (Fed. Cir. 2013) .......................................................................... 49
`
`Duncan v. Walker,
`533 U.S. 167 (2001) ............................................................................................ 35
`
`EBC, Inc. v. Clark Bldg. Sys., Inc.,
`618 F.3d 253 (3d Cir. 2010) ............................................................................... 58
`
`Elan Corp. v. Andrx Pharms., Inc.,
`366 F.3d 1336 (Fed. Cir. 2004) .......................................................................... 53
`
`
`
`iii
`
`

`
`TABLE OF AUTHORITIES
`(continued)
`
`Envirotech Corp. v. Westech Eng’g Inc.,
`
`904 F.2d 1571 (Fed. Cir. 1990) .......................................................................... 53
`
`Page(s)
`
`Enzo Biochem, Inc. v. Gen-Probe, Inc.,
`424 F.3d 1276 (Fed. Cir. 2005) .................................................................... 52, 55
`
`Excelsior Med. Corp. v. Lake,
`IPR2013-00494, Paper 10 (Feb. 6, 2014) ........................................................... 60
`
`FCC v. Fox Television Stations, Inc.,
`556 U.S. 502 (2009) ............................................................................................ 37
`
`Fed. Energy Admin. v. Algonquin SNG, Inc.,
`426 U.S. 548 (1976) ............................................................................................ 43
`
`In re Fisher,
`427 F.2d 833 (C.C.P.A. 1970) ............................................................................ 56
`
`Garcia v. United States,
`469 U.S. 70 (1984) .............................................................................................. 40
`
`Gentry Gallery, Inc. v. Berkline Corp.,
`134 F.3d 1473 (Fed. Cir. 1988) .................................................................... 27, 28
`
`Gilead Scis., Inc. v. Natco Pharma Ltd.,
`753 F.3d 1208 (Fed. Cir. 2014) .......................................................................... 44
`
`Grp. One, Ltd. v. Hallmark Cards, Inc.,
`254 F.3d 1041 (Fed. Cir. 2001) .......................................................................... 53
`
`Holder v. Martinez Gutierrez,
`132 S. Ct. 2011 (2012) ........................................................................................ 38
`
`Hulu LLC v. Intertainer, Inc.,
`IPR2014-01456, Paper 8 (Mar. 6, 2015) ............................................................ 60
`
`ICU Med., Inc. v. Alaris Med. Sys.,
`558 F.3d 1368 (Fed. Cir. 2009) .......................................................................... 29
`
`iv
`
`

`
`TABLE OF AUTHORITIES
`(continued)
`
`Linear Tech. Corp. v. Micrel, Inc.,
`
`275 F.3d 1040 (Fed. Cir. 2001) .......................................................................... 53
`
`Page(s)
`
`Moleculon Research Corp. v. CBS Inc.,
`793 F.2d 1261 (Fed. Cir. 1986) .......................................................................... 28
`
`In re Omeprazole Patent Litigation,
`536 F.3d 1361 (Fed. Cir. 2008) .......................................................................... 57
`
`Paroline v. United States,
`134 S. Ct. 1710 (2014) .................................................................................. 34, 35
`
`Pfaff v. Wells Elecs., Inc.,
`525 U.S. 55 (1998) ......................................................................33, 39, 56, 57, 59
`
`PIN-NIP, Inc. v. Platte Chem. Co.,
`304 F.3d 1235 (Fed. Cir. 2002) .......................................................................... 29
`
`Prism Pharma Co. v. Choogwae Pharma Corp.,
`IPR2014-00315, Paper 14 (July 8, 2014) ........................................................... 60
`
`Reiffin v. Microsoft Corp.,
`214 F.3d 1342 (Fed. Cir. 2000) .......................................................................... 30
`
`Space Systems/Loral, Inc. v. Lockheed Martin Corp.,
`271 F.3d 1076 (Fed. Cir. 2001) .............................................................. 56, 57, 58
`
`Sparton Corp. v. United States,
`77 Fed. Cl. 1 (Fed. Cl. 2007) .............................................................................. 32
`
`Square, Inc. v. Unwired Planet, LLC,
`CBM2014-00156, Paper 40 (Dec. 22, 2015) ...................................................... 32
`
`In re Swanson,
`540 F.3d 1368 (Fed. Cir. 2008) .......................................................................... 40
`
`Symantec Corp. v. Finjan, Inc.,
`IPR2015-01548, Paper 9 (Jan. 14, 2016) ............................................................ 31
`
`v
`
`

`
`TABLE OF AUTHORITIES
`(continued)
`
`United States v. Alaska,
`
`521 U.S. 1 (1997) ................................................................................................ 38
`
`Page(s)
`
`United States v. Standard Brewery, Inc.,
`251 U.S. 210 (1920) ............................................................................................ 36
`
`Univ. of Rochester v. G.D. Searle & Co.,
`358 F.3d 916 (Fed. Cir. 2004) ............................................................................ 30
`
`In re Wright,
`999 F.2d 1557 (Fed. Cir. 1993) .......................................................................... 57
`
`In re Zletz,
`893 F.2d 319 (Fed. Cir. 1989) ............................................................................ 61
`
`Statutes
`
`35 U.S.C.
`§ 102(a)(1) .................................................................................... 4, 33, 34, 36, 46
`§ 102(b) ............................................................................................................... 38
`§ 321(a) ............................................................................................................... 45
`§ 325(d) ......................................................................................................... 60, 61
`§ 326(a)(5) .......................................................................................................... 45
`§ 326(a)(11) ........................................................................................................ 45
`
`Regulations
`
`37 C.F.R.
`§ 42.65 ........................................................................................................... 31, 32
`§ 42.200(b) .......................................................................................................... 61
`
`vi
`
`

`
`TABLE OF AUTHORITIES
`(continued)
`
`Page(s)
`
`Other Authorities
`
`157 Cong. Rec.
`H4429 (daily ed. June 22, 2011) ......................................................................... 43
`S1042 (daily ed. Mar. 1, 2011) ..................................................................... 36, 49
`S1208-09 (daily ed. Mar. 3, 2011) ...................................................................... 45
`S1370 (daily ed. Mar. 8, 2011) ........................................................................... 41
`S1371 (daily ed. March 8, 2011) .................................................................. 44, 45
`S1496 (daily ed. Mar. 8, 2011) ..................................................................... 36, 49
`S1496 (daily ed. March 9, 2011) ........................................................................ 42
`S5319 (daily ed. Sept. 6, 2011) ........................................................................... 43
`S5320 (daily ed. Sept. 6, 2011) ........................................................................... 43
`S5431 (daily ed. Sept. 8, 2011) ........................................................................... 43
`
`AIA Examination Guidelines,
`78 Fed. Reg. 11059 (Feb. 14, 2013) ....................................................... 36, 47, 49
`
`Office Patent Trial Practice Guide,
`77 Fed. Reg. 48756 (Aug. 14, 2012) .................................................................. 31
`
`MPEP § 2152.02(d).............................................................................................. 4, 46
`
`H.R. Rep. No. 112-98 (2011) ............................................................................. 39, 40
`
`S. Rep. No. 110-259 (2008) ..................................................................................... 40
`
`S. Rep. No. 111-18 (2009) ....................................................................................... 45
`
`
`
`vii
`
`

`
`Case PGR2016-00008
`
`LIST OF EXHIBITS
`
`Exhibit
`2001
`
`2002
`
`2003
`
`2004
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`2012
`
`Description
`Excerpts from Trial Tr. (Calderari), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 2, 2015).
`Excerpts from Trial Tr. (Calderari), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 3, 2015).
`Excerpts from Trial Tr. (Fruehauf), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 12-2867 (D.N.J. June 4, 2015)
`Excerpts from Trial Tr. (Kirsch), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 5, 2015)
`2005 RESERVED
`Excerpts from Trial Tr. (Marriott), Helsinn Healthcare, S.A. v. Dr.
`2006
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 9, 2015).
`Excerpts from Trial Tr. (Benhamza), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 9, 2015).
`Excerpts from Trial Tr. (Candiotti), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 10, 2015).
`Excerpts from Trial Tr. (Peck), Helsinn Healthcare, S.A. v. Dr. Reddy’s
`Labs., Ltd., No. 11-3962 (D.N.J. June 11, 2015).
`Excerpts from Trial Tr. (Saab), Helsinn Healthcare, S.A. v. Dr. Reddy’s
`Labs., Ltd., No. 11-3962 (D.N.J. June 12, 2015).
`Excerpts from Trial Tr. (Markman), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 15, 2015).
`Excerpts from Trial Tr. (Amidon), Helsinn Healthcare, S.A. v. Dr.
`Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. June 15, 2015)
`2013 RESERVED
`2014 RESERVED
`2015
`Excerpts of Defendants’ Contested Facts, from Final Pretrial Order,
`Helsinn Healthcare, S.A. v. Dr. Reddy’s Labs., No. 11-3962 (D.N.J.
`Apr. 17, 2015).
`2016 RESERVED
`Excerpts from Christopher Fausel Deposition Tr., Helsinn Healthcare,
`2017
`S.A. v. Dr. Reddy’s Labs., Ltd., No. 12-2867 (D.N.J. Apr. 15, 2016).
`Excerpts from Joanne Broadhead Deposition Tr., Helsinn Healthcare,
`S.A. v. Dr. Reddy’s Labs., Ltd., No. 12-2867 (D.N.J. Apr. 29, 2016).
`Excerpts from Bertram Spilker Deposition Tr., Helsinn Healthcare, S.A.
`v. Dr. Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. Jan.17, 2014).
`
`2018
`
`2019
`
`
`
`viii
`
`

`
`Case PGR2016-00008
`
`LIST OF EXHIBITS
`(continued)
`
`2020
`
`Excerpts from Bertram Spilker Deposition Tr., Helsinn Healthcare, S.A.
`v. Dr. Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. Jan.16, 2014).
`2021 RESERVED
`2022 RESERVED
`2023 RESERVED
`2024
`Excerpts from Rebuttal Expert Report of Tanios Bekaii-Saab, M.D.,
`Helsinn Healthcare, S.A. v. Dr. Reddy’s Labs., Ltd., No. 11-3962 (D.N.J.
`Oct. 25, 2013) (“Saab Initial ANDA Action Report”).
`2025 RESERVED
`2026 RESERVED
`Excerpts from Expert Report of Lee Kirsch, Ph.D., Helsinn Healthcare,
`2027
`S.A. v. Dr. Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. Sept. 9, 2013)
`(“Kirsch ANDA Action Report”) (as submitted in prosecution of U.S.
`Patent Application No. 13/901,830).
`2028 RESERVED
`Excerpts from Reply Expert Report of Patrick P. DeLuca, Ph.D., Helsinn
`2029
`Healthcare, S.A. v. Dr. Reddy’s Labs., Ltd., No. 11-3962 (D.N.J. Nov.
`21, 2013) (“DeLuca Reply ANDA Action Report”) (as submitted in
`prosecution of U.S. Patent Application No. 13/901,830).
`2030 RESERVED
`2031 RESERVED
`2032 RESERVED
`2033 RESERVED
`2034 RESERVED
`2035 RESERVED
`2036 RESERVED
`2037 RESERVED
`2038 RESERVED
`2039 Kelly B. Pendergrass, Options in the Treatment of Chemotherapy-
`Induced Emesis, 6 Cancer Prac. 276 (Sept.-Oct. 1998) (“Pendergrass
`1998”).
`2040 RESERVED
`2041 RESERVED
`2042 RESERVED
`2043 RESERVED
`2044 RESERVED
`
`ix
`
`

`
`Case PGR2016-00008
`
`LIST OF EXHIBITS
`(continued)
`
`2052
`
`2045 RESERVED
`Joe Matal, A Guide to the Legislative History of the America Invents
`2046
`Act: Part I of II, 21 Fed. Cir. B.J. 435 (2012)
`2047 Merriam-Webster’s Collegiate Dictionary 879 (11th ed. 2005).
`2048 RESERVED
`2049 RESERVED
`2050 RESERVED
`2051 A Dose-Ranging Efficacy, Safety, and Pharmacokinetic Study of Single
`Intravenous Doses of RS-25259 for Prevention of Nausea and Vomiting
`in Chemotherapy-Naive Cancer Patients Receiving Highly Emetogenic
`Chemotherapy, Study No. 25259S2330 (“Study 2330 Report”).
`PALO-99-03 Clinical Study Report, dated July 19, 2002 (“PALO-99-03
`Report”).
`2053 Helsinn’s NDA 21-372 Submission Letter dated Sept. 26, 2002.
`2054 Highlights of Prescribing Information, ALOXI® (palonosetron HCl)
`Injection for Intravenous Use, revised Feb. 2008.
`2055 Approval letter from FDA to Helsinn for New Drug Application No. 21-
`372 (ALOXI®) (July 25, 2003).
`2056 RESERVED
`2057 RESERVED
`2058 RESERVED
`2059 RESERVED
`2060 RESERVED
`2061 RESERVED
`2062 RESERVED
`2063 RESERVED
`2064 RESERVED
`2065 RESERVED
`2066 RESERVED
`2067 RESERVED
`2068 RESERVED
`2069
`Information Disclosure Sheet, filed Mar. 5, 2015, in U.S. Patent
`Application No. 13/901,830 (Signed July 27, 2015).
`2070 RESERVED
`2071 RESERVED
`2072 Declaration of Daniele Bonadeo, signed Feb. 9, 2009, in U.S. Patent
`
`x
`
`

`
`Case PGR2016-00008
`
`LIST OF EXHIBITS
`(continued)
`
`2073
`
`Application No. 11/186,311 (“2/9/09 Bonadeo Decl.”).
`Summary of Interview, conducted June 13, 2013, submitted June 17,
`2013 in U.S. Patent Application No. 13/901,830.
`2074 RESERVED
`Petition, Dr. Reddy’s Labs. v. Helsinn Healthcare, S.A., PGR2016-
`2075
`00007, Paper 1 (P.T.A.B. Feb. 5, 2016) (“DRL PGR1”).
`2076 RESERVED
`2077 Declaration of Christopher Fausel, signed Feb. 5, 2016, submitted in
`DRL PGR1 as Ex 1026 (“Fausel Decl. (DRL PGR1)”).
`2078 RESERVED
`2079 RESERVED
`2080 RESERVED
`2081 Helsinn Healthcare S.A., v. Dr. Reddy’s Labs., Ltd., No. 11-3962, 2016
`WL 832089 (D.N.J. Mar. 3, 2016) (the “Supplemental ANDA
`Opinion”).
`2082 Complaint, Helsinn Healthcare S.A., v. Dr. Reddy’s Labs., Ltd., No. 12-
`2867 (D.N.J. May 11, 2012).
`2083 Complaint, Helsinn Healthcare S.A., v. Dr. Reddy’s Labs., Ltd., No. 14-
`4274 (D.N.J. July 7, 2014).
`2084 Amended Complaint, Helsinn Healthcare S.A., v. Dr. Reddy’s Labs.,
`Ltd., No. 14-4274 (D.N.J. Sep. 2, 2015).
`2085 Corrected Brief for Defendants-Appellants Teva Pharmaceuticals USA,
`Inc., Teva Pharmaceutical Industries, Ltd., No. 2016-1284 (Fed. Cir.
`filed Mar. 8, 2016)
`2086 Brief for the United States as Amicus Curiae in Support of Appellees,
`Helsinn Healthcare S.A. v. Teva Pharms. USA, Inc., No. 2016-1284
`(Fed. Cir. filed May 2, 1016) (“U.S. Helsinn Brief”).
`En Banc Brief for the United States as Amicus Curiae in Support of
`Appellant, Medicines Co. v. Hospira, Inc., Nos. 2014-1469, 2014-1504
`(Fed. Cir. filed Mar. 2, 2016) (“U.S. Medicines Brief”).
`2088 Brief of Amicus Curiae Congressman Lamar Smith in Support of
`Appellees, Helsinn Healthcare S.A. v. Teva Pharms. USA, Inc., No.
`2016-1284 (Fed. Cir. filed Apr. 21, 2016).
`2089 Brief for Amicus Curiae Pharmaceutical Research and Manufacturers of
`America and Biotechnology Innovation Organization in Support of
`Plaintiffs-Appellees, Helsinn Healthcare S.A. v. Teva Pharms. USA,
`Inc., Nos. 2016-1284, -1797 (Fed. Cir. filed May 2, 2016).
`
`2087
`
`xi
`
`

`
`Case PGR2016-00008
`
`LIST OF EXHIBITS
`(continued)
`
`2090 Brief of Amicus Curiae American Intellectual Property Law Association
`in Support of Plaintiffs-Appellees, Helsinn Healthcare S.A. v. Teva
`Pharms. USA, Inc., Nos. 2016-1284, -1797 (Fed. Cir. filed May 2,
`2016).
`2091 Brief of Amicus Curiae The Naples Roundtable, Inc. in Support of
`Plaintiffs-Appellees, Helsinn Healthcare S.A. v. Teva Pharms. USA,
`Inc., No. 2016-1284 (Fed. Cir. filed Apr. 27, 2016).
`
`
`
`xii
`
`

`
`
`
`I.
`
`Introduction
`
`
`
`Case PGR2016-00008
`
`Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc.
`
`(collectively, “DRL” or Petitioner) allege that claims 1-19 of U.S. Patent No.
`
`9,173,942 (“the ’942 patent”) are invalid (1) for lack of written description and
`
`(2) under the on-sale bar. (Pet. at 6.) DRL’s arguments apply the wrong legal
`
`standards and should be rejected. A person of ordinary skill in the art (“POSA”)1
`
`would readily understand that the full scope of the ’942 patent claims, which
`
`require the same ingredients in the same amounts disclosed in preferred
`
`embodiments of the invention, is supported by the written description. Those
`
`claims, which are subject to the Leahy-Smith America Invents Act (“AIA”), are
`
`also not invalid under the on-sale bar because: (1) there was no commercial offer
`
`for sale of the claimed inventions; (2) there was no offer for sale that made the
`
`claimed inventions “available to the public”; and (3) the claimed inventions were
`
`not ready for patenting before the critical date. DRL’s Petition should be denied
`
`because it cannot establish that it is more likely than not that at least one of the
`
`’942 patent claims is unpatentable.
`
`
`1 DRL does not define a POSA in its Petition. Patent Owner, however, agrees with
`
`DRL’s position in the simultaneously filed PGR that the definition of a POSA used
`
`in the ANDA action should be used in this PGR. (Ex. 2075, DRL PGR1 at 27-28.)
`
`1
`
`

`
`
`
`
`
`Case PGR2016-00008
`
`The ’942 patent is one of several related patents with claims covering
`
`Aloxi®, Patent Owner’s highly successful — and extensively copied — drug
`
`product indicated to prevent nausea and vomiting, or “emesis” (see, e.g., Ex. 1001,
`
`col. 1:25-28), in patients receiving cancer chemotherapy. While several 5-HT3s,2
`
`including Aloxi®, have been FDA-approved to prevent “acute” chemotherapy-
`
`induced nausea and vomiting (“CINV”), Aloxi® is the only one approved to
`
`prevent “delayed” CINV.3 With over $3.6 billion in U.S. sales, Aloxi® has helped
`
`countless people cope with the rigors of chemotherapy. (Ex. 2006, 6/9/15
`
`(Marriott) Trial Tr. at 158:24-159:4.4) Indeed, Aloxi® is hailed by DRL’s own
`
`experts as “a wonderful product” (Ex. 2011, 6/10/15 (Markman) Trial Tr. at 8:2)
`
`that is “used most of the time” despite the availability of lower-priced, generic 5-
`
`2 The term “5-HT3s” refers to a class of compounds that block 5-HT3 receptors and
`
`disrupt the serotonin pathway, which is implicated in emesis. (Ex. 2039 at 277.)
`
`3 Emesis occurring within 24 hours after the administration of chemotherapy is
`
`commonly referred to as “acute CINV,” while emesis occurring more than 24
`
`hours after the administration of chemotherapy is referred to as “delayed CINV.”
`
`(Ex. 2010, 6/12/15 (Saab) Trial Tr. at 18:16-19:5.)
`
`4 Certain exhibits submitted herewith have been excerpted to exclude confidential
`
`information.
`
`2
`
`

`
`
`
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`HT3s (Ex. 2017, 4/15/16 (Fausel) Dep. Tr. at 279:8-280:1).
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`To be sure, DRL has already tried unsuccessfully to invalidate claims of
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`patents related to the ’942 patent. In Civil Action No. 11-3962 in the District of
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`New Jersey (“the ANDA action”), the court rejected DRL’s arguments that similar
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`claims from related patents were invalid for obviousness, lack of written
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`description, or under the on-sale bar. (Ex. 1041, Memorandum Opinion at 4-5.)
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`While settling out of the case shortly before the court issued its decision, DRL
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`fully participated in the ANDA action trial, including and through closing
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`arguments. This Petition and the other concurrently filed petition appear to have
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`been submitted in an attempt to circumvent the outcome of the ANDA action.
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`DRL’s arguments, however, should be rejected.
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`In Ground 1, DRL asserts that the ’942 patent claims are invalid for lack of
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`written description because they allegedly could include unstable palonosetron
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`formulations. (Pet. at 24-30.) In making this argument, DRL miscomprehends the
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`claimed inventions. The written description discloses that “palonosetron
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`concentration is a critical factor in chemical stability with greatest stability seen at
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`the lowest palonosetron concentrations” (Ex. 1001, col. 7:33-43), and that a 0.05
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`mg/mL palonosetron concentration is the “most optimal[]” in this regard (id. at
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`col. 5:1-15). Thus, the ’942 patent claims — all of which require a 0.05 mg/mL
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`palonosetron concentration, as well as stabilizing ingredients in preferred
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`concentrations and/or the optimal pH of 4-6 — are perfectly consistent with, and
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`fully supported by, the written description. (See § III.A, infra.) Based on this
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`disclosure, a POSA “would immediately discern the claimed formulation[s] in that
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`disclosure,” Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1308-09 (Fed. Cir. 2015)
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`(citation omitted), which is sufficient to satisfy the written description requirement.
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`DRL’s cited case law, all of which relates to structure or method steps that were
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`not included in the claims, has no relevance where, as here, the allegedly missing
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`limitation is an inherent property of the claimed formulations, which Reddy
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`admitted in the ANDA action. (See § III.B-C, infra.)
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`In Ground 2, DRL contends that the ’942 patent claims are invalid under the
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`on-sale bar. (Pet. at 30-61.) Under its plain meaning, legislative history, and
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`underlying policy, AIA 35 U.S.C. § 102(a)(1) requires an alleged offer for sale to
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`have made the claimed invention “available to the public.” (See § IV.A.1, infra.)
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`This statutory construction is consistent with the Patent Office’s own
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`interpretation, which was recently confirmed by an amicus brief filed by the United
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`States in the ANDA action appeal. See, e.g., MPEP § 2152.02(d). (See also Ex.
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`2086, U.S. Helsinn Br. at 4-6.) Under the correct statutory interpretation, there
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`was no on-sale bar because Patent Owner’s agreement with MGI Pharma, Inc. did
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`not make the claimed formulation “available to the public.” (See § IV.A.2, infra.)
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`In any event, under either party’s statutory interpretation, the claims are not
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`unpatentable under an on-sale bar because Patent Owner’s agreement with MGI
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`was not an offer for sale of the claimed invention (see § IV.B, infra) and the
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`claimed invention was not ready for patenting before the critical date (see § IV.C,
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`infra).
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`In sum, DRL has not shown that it is more likely than not that at least one of
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`the claims challenged in the Petition is unpatentable. Patent Owner therefore
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`respectfully submits that the Board should decline to institute a trial.
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`II. Background
`A. Aloxi® Is a Breakthrough Drug
`Product for Patients Suffering from CINV
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`Nausea and vomiting are the body’s natural responses to noxious stimuli,
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`and serve the critical function of expelling harmful substances from the body. (Ex.
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`2024, Saab Initial ANDA Action Report at ¶ 16.) Medications, such as
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`chemotherapy, can also stimulate these same physiologic pathways. (Id. at ¶ 17.)
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`The trauma to patients from CINV can be severe. As Patent Owner’s expert,
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`Dr. Tanios Bekaii-Saab, testified in the ANDA action, CINV has long been
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`recognized as one of its most dreaded side effects. (Ex. 2010, 6/12/15 (Saab) Trial
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`Tr. at 14:23-15:25.) In fact, the CINV symptoms were so severe for some patients
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`that they refused to continue chemotherapy. (Id.) And to the extent cancer that
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`was previously in remission returned, some patients were reluctant to restart
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`chemotherapy based on their past experiences. (Id.)
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`By 1991, a new form of treatment had been approved for patients suffering
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`from acute (i.e., within the first 24 hours following chemotherapy) CINV: 5-HT3s.
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`(Id. at 18:3-15.) According to Dr. Saab, the FDA-approved 5-HT3s “were effective
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`in helping with the acute episodes” of CINV and “a very welcome addition before
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`2003.” (Ex. 2010, 6/12/15 (Saab) Trial Tr. at 18:7-15.)
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`These 5-HT3s, however, did not effectively treat delayed CINV occurring
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`after 24 hours. Delayed CINV is a particularly debilitating condition given that the
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`patient has likely left the care of medical professionals when the symptoms first
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`arrive, and “will present with severe episodes of nausea and vomiting up to 20, 30
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`times.” (Id. at 19:12-17.) Because there is no cure for delayed emesis once
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`symptoms start, patients were kept in hospitals and supported with intravenous
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`fluids for up to a week until the symptoms subsided on their own. (Id.) As Dr.
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`Saab testified, before Aloxi®, “we didn’t have real good strategies at the time to
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`actually prevent or treat delayed emesis.” (Id. at 20:2-20:7.)
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`In July 2003, more than ten years after the first 5-HT3 was approved, the
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`FDA approved Aloxi® for use in preventing acute and delayed nausea and
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`vomiting following chemotherapy. (Id. at 65:11-67:7.) To this day, Aloxi® is the
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`only 5-HT3 approved for prevention of delayed CINV. (Id. at 43:7-9, 67:1-7.)
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`Major cancer-related professional society guidelines identify Aloxi® as a preferred
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`treatment for the management of moderately emetogenic CINV. (Id. at 79:25-
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`80:11.) With over $3.6 billion in U.S. sales, Aloxi® has helped countless people
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`cope with the side effects of chemotherapy. (Ex. 2006, 6/9/15 (Marriott) Trial Tr.
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`at 158:24-159:4.) Indeed, Aloxi® was hailed as “a wonderful product” that was
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`effective for delayed CINV where other setrons were not by DRL’s own expert in
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`the ANDA action. (Ex. 2011, 6/10/15 (Markman) Trial Tr. at 7:14-8:19, 9:20-
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`10:6.) One of DRL’s PGR declarants, Dr. Fausel, similarly testified in a related
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`action that Aloxi® is his “workhorse” 5-HT3 antiemetic, i.e., the 5-HT3 antiemetic
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`that his group “use[s] most of the time,” despite the availability of less-expensive
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`generic 5-HT3s. (Ex. 2017, 4/15/16 (Fausel) Dep. Tr. at 279:8-280:3.)
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`B.
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`The Development of Aloxi®
`Roche’s Early Palonosetron Work
`1.
`The active pharmaceutical ingredient in Aloxi®, palonosetron, was
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`discovered in the early 1990s by scientists at Syntex (USA) Inc. (which was later
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`acquired by Roche Palo Alto LLC). (Ex. 2001, 6/2/15 (Calderari) Trial Tr. at
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`114:5-11, 127:2-7.) Roche conducted Phase II clinical trials with palonosetron
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`dissolved in simple phosphate-buffered saline solutions, i.e., not the claimed
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`formulations. (Ex. 2002, 6/3/15 (Calderari) Trial Tr. at 10:9-16.) In these studies,
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`Roche investigated the potential therapeutic effect (if any) of ascending
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`palonosetron doses on CINV. (Ex. 2009, 6/11/15 (Peck) Trial Tr. at 39:8-24.)
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`One such Phase II trial, Study 2330, involved the administration of five
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`palonosetron doses ranging from 1-90 μg/kg (equating to roughly 0.1 mg-6 mg) to
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`161 cancer patients on cis