Case IPR2015-01553
`Patent No. 8,729,094
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`
`Patent No. 8,729,094
`Issue Date: May 20, 2014
`Title: LIQUID PHARMACEUTICAL FORMULATIONS OF PALONOSETRON
`____________________________
`
`Inter Partes Review No. IPR2015-01553
`
`__________________________________________________________________
`
`CORRECTED PETITION FOR INTER PARTES REVIEW OF
`CLAIMS 22-27 AND 30 OF U.S. PATENT NO. 8,729,094
`AND MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________________________
`
`DR. REDDY’S LABORATORIES, LTD. and
`DR. REDDY’S LABORATORIES, INC.
`Requestors
`
`v.
`
`HELSINN HEALTHCARE S.A. and ROCHE PALO ALTO LLC
`Patent Owner
`
`
`
`

`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`TABLE OF CONTENTS
`
`Page
`
`TABLE OF AUTHORITIES ................................................................................... iii
`
`EXHIBIT LIST ........................................................................................................ iv
`
`STATEMENT OF REASONS FOR RELIEF REQUESTED ................................... 5 
`
`I. 
`
`II. 
`
`INTRODUCTION AND SUMMARY OF ARGUMENT .............................. 5 
`
`THE CLAIMS UNDER CONSIDERATION ................................................. 7 
`
`III.  THE SPECIFICATION AND PROSECUTION HISTORY OF THE
`‘094 PATENT .................................................................................................. 8 
`
`A.  The Specification Of The ‘094 Patent ...................................................... 8 
`
`B.  The Prosecution History Of The ‘094 Patent ......................................... 10 
`
`IV.  CLAIM CONSTRUCTION .......................................................................... 14 
`
`A.  Optionally ............................................................................................... 14 
`
`B.  Acute And Delayed ................................................................................. 15 
`
`C.  Chelating Agent ...................................................................................... 16 
`
`V. 
`
`CLAIMS 22-27 AND 30 OF THE ‘094 PATENT WOULD HAVE BEEN
`OBVIOUS OVER EGLEN (EXH.1011) WHEN TAKEN IN VIEW OF
`CHELLY (EXH.1012), GIBSON (EXH.1014), AND THE 2001
`PHYSICIANS’ DESK REFERENCE (EXHS. 1015-1017) ............................ 16 
`
`A.  The Level Of Ordinary Skill In The Art ................................................. 18 
`
`B.  Scope And Content Of The Prior Art ..................................................... 21 
`
`1.  The “Treatment” Limitations Of Claim 22 ...................................... 21 
`
`a. 
`
`b. 
`
`Background ............................................................................ 21 
`
`Eglen ...................................................................................... 23 
`
`
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`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`c. 
`
`Chelly ..................................................................................... 26 
`
`d. 
`
`Eglen And Chelly Combined ................................................. 27 
`
`2.  Dose Adjustments ............................................................................ 30 
`
`3.  A POSA’s Use Of Data To Select A Dose ...................................... 32 
`
`4.  Tang (Exh.1019) .............................................................................. 34 
`
`5.  The Product Recitations Of The Claims .......................................... 35 
`
`C.  Differences Between The Claims And The Prior Art ............................. 42 
`
`D.  Dependent Claims ................................................................................... 49 
`
`1.  Claim 23 ........................................................................................... 49 
`
`2.  Claim 24 ........................................................................................... 50 
`
`3.  Claim 25 ........................................................................................... 50 
`
`4.  Claim 26 ........................................................................................... 52 
`
`5.  Claim 27 ........................................................................................... 52 
`
`6.  Claim 30 ........................................................................................... 53 
`
`E.  Claim Chart ............................................................................................. 53 
`
`VI.  CONCLUSION .............................................................................................. 57 
`
`
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`ii
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`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`TABLE OF AUTHORITIES
`
`
`CASES
`
`Page(s)
`
`3M v. Chemque, Inc.,
`303 F.3d 1294 (Fed. Cir. 2002) .......................................................................... 18
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ...................................................................... 45, 46
`
`Asyst Techs. Inc. v. Emtrak, Inc.,
`544 F.3d 1310 (Fed. Cir. 2008) .......................................................................... 44
`
`Atlas Powder Co. v. E. I. Du Pont de Nemours & Co.,
`750 F.2d 1569 (Fed. Cir. 1984) .......................................................................... 32
`
`In re Baxter Travenol Labs.,
`952 F.2d 388 (Fed. Cir. 1991) ............................................................................ 44
`
`In re Cuozzo Speed Techs., LLC,
`No. 2014-1301, Slip. Op. (Fed. Cir. Feb. 4, 2015) ............................................. 14
`
`Ericsson Inc. v. Intellectual Ventures II, LLC,
`IPR 2014-01412 (PTAB Mar. 18, 2015) ............................................................ 15
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ...................................................................... 18, 43
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................ 17
`
`KSR Int'l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................................ 17
`
`In re Merck & Co.,
`800 F.2d 1091 (Fed. Cir. 1986) .......................................................................... 32
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1373 (Fed. Cir. 2012) ......................................................................... 18
`
`
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`iii
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`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`Oracle Corp. v. Thought, Inc.,
`IPR 2014-00118 (PTAB Apr. 25, 2014) ............................................................ 15
`
`Par Pharm. Inc. v. TWI Pharms., Inc.,
`773 F.3d 1186, No. 2014-1391, 2014 U.S. App.
` LEXIS 22737 (Fed. Cir. Dec. 3, 2014) .............................................................. 17
`
`Univ. of Rochester v. G.D. Searle & Co.,
`249 F. Supp. 2d 216 (W.D.N.Y. 2033) ............................................................... 20
`
`Takeda Pharm. Co. v. Mylan Inc.,
`Case No. 13-4001, 2014 U.S. Dist. LEXIS 159527
` (N.D. Cal. Nov. 11, 2014) .................................................................................. 20
`
` Warner Chilcott Co., LLC v. Lupin Ltd,
`Civ. Action Nos. 11-5048, 12-2928,
`2014 U.S. Dist. LEXIS 6228 (D.N.J. Jan. 17, 2014) .......................................... 19
`
`STATUTES, RULES & OTHER AUTHORITIES
`
`35 U.S.C. § 102 .................................................................................................passim
`
`35 U.S.C. § 103 .............................................................................................. 4, 11, 17
`
`37 C.F.R. § 42.100(b) .............................................................................................. 14
`
`
`
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`iv
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`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`EXHIBIT LIST
`
`Exhibit # Reference
`1001
`U.S. Patent No. 8,729,094
`1002
`U.S. Patent No. 7,947,724
`1003
`U.S. Patent No. 7,947,725
`1004
`U.S. Patent No. 7,960,424
`1005
`U.S. Patent No. 8,598,219
`1006
`Complaint for Patent Infringement, Helsinn Healthcare S.A. and
`Roche Palo Alto LLC v. Dr. Reddy’s Laboratories, Ltd. and
`Dr. Reddy’s Laboratories, Inc., U.S.D.C.N.J. Civil Action
`No. 3:14-cv-04274-MLC-DEA
`Complaints for Patent Infringement, Helsinn Healthcare S.A. and
`Roche Palo Alto LLC v. Dr. Reddy’s Laboratories, Ltd. and
`Dr. Reddy’s Laboratories, Inc., et al. U.S.D.C.N.J. Civil Action
`No. 3:11-cv-03962-MLC-TJB filed 7/8/2011; Helsinn Healthcare
`S.A. and Roche Palo Alto LLC v. Dr. Reddy’s Laboratories, Ltd.,
`Dr. Reddy’s Laboratories, Inc., et al., U.S.D.C.N.J. Civil Action
`Nos. 3:11-cv-05579-MLC-DEA filed 9/23/2011; Helsinn
`Healthcare S.A. and Roche Palo Alto LLC v. Dr. Reddy’s
`Laboratories, Ltd., Dr. Reddy’s Laboratories, Inc., et al.,
`3:13-cv-05815-MLC-DEA filed 12/27/2013; and Helsinn
`Healthcare S.A. and Roche Palo Alto LLC v. Dr. Reddy’s
`Laboratories, Ltd. & Dr. Reddy’s Laboratories, Inc., U.S.D.C.N.J.
`Civil Action No. 3:12-cv-02867-MLC-DEA filed 5/12/2012
`Serial No. 13/902,132 Final Rejection, Dec. 6, 2013
`Serial No. 13/902,132, Amendment After Final, Feb. 21, 2014
`U.S. Patent No. 5,202,333 (“Berger”)
`Eglen et al., Pharmacological characterization of RS 25259-197, a
`novel and selective 5-HT3 receptor antagonist, in vivo, 114 British
`J. Pharmacol. 860-66 (1985) (“Eglen”)
`Chelly et al., Oral RS-25259 Prevents Postoperative Nausea and
`Vomiting Following Laparoscopic Surgery, Abstracts of Scientific
`Papers 1996 Annual Meeting, 85 Anesthesiology, No. 34, A21
`(Sept. 1996) (“Chelly”)
`
`1007
`
`1008
`1009
`1010
`1011
`
`1012
`
`
`
`v
`
`

`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
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`Exhibit # Reference
`1013
`Gralla et al., Recommendations for the Use of Antiemetics:
`Evidence-Based, Clinical Practice Guidelines, 17 J. Clin.
`Oncology, No. 9, 2971-94 (Sept. 1999)
`Gibson, Parenteral Dosage Forms, Pharmaceutical Preformulation
`and Formulation, A Practical Guide from Candidate Drug Selection
`to Commercial Dosage Form 175-237, 295-354 (2001)
`ZOFRAN (2001). In Physician’s Desk Reference 1503-07 (55th
`ed.) Montvale, NJ: PDR Network
`KYTRIL (2001). In Physician’s Desk Reference 3104-06 (55th ed.)
`Montvale, NJ: PDR Network
`ANZEMET (2001). In Physician’s Desk Reference 680-83 (55th
`ed.) Montvale, NJ: PDR Network
`Gaia Piraccini et al., An Interesting 5-HT3 Receptor Antagonist
`Antiemetic for Patients Undergoing Chemotherapy-Based
`Conditioning Regimens, Abstract 5169, 98(11) J. of the American
`Society of Hematology 350b (Nov. 16, 2001)
`Tang et al., The Efficacy of RS-25259, a Long-Acting Selective
`5-HT3 Receptor Antagonist, for Preventing Postoperative Nausea
`and Vomiting After Hysterectomy Procedures, 87 Anesth. Analg.,
`462-7 (1998) (“Tang”)
`Lauri P. Cohen, Many Medicines Are Potent Years Past Expiration
`Dates, Wall St. J., March 28, 2000.
`1021
`Declaration of William McGuire, M.D.
`1022 William McGuire, M.D. curriculum vitae
`1023
`Declaration of David G. Frame, Pharm.D.
`1024
`David G. Frame, Pharm.D. curriculum vitae
`1025
`Tr. transcript Dr. Kirsch 19:12-20:23, June 5, 2015 (what is a
`POSA)
`Tr. transcript Dr. Candiotti 18:19-20:4, June 10, 2015 (what is a
`POSA)
`Gandara et al., Consensus Proposal for 5-HT3 Antagonists in the
`Prevention of Acute Emesis Related to Highly Emetogenic
`Chemotherapy, Support Care Cancer (1998) 6:237-243
`(“Gandara”)
`
`1026
`
`1027
`
`
`
`vi
`
`

`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`1034
`1035
`1036
`
`1037
`1038
`1039
`
`1040
`1041
`1042
`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
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`Exhibit # Reference
`1028
`Tr. transcript Dr. Frame direct 109:2-110:15, 121:18-123:3,
`124:20-128:4, June 8, 2015 (PONV to CINV)
`Tr. transcript Dr. Candiotti direct 82:12-83:15, June 10, 2015
`(PONV to CINV)
`Tr. Transcript Dr. Frame direct 107:14-108:25, June 8, 2015 (oral
`to IV)
`U.S. Food and Drug Administration. Estimating the safe starting
`dose in clinical trials for therapeutics in adult healthy volunteers
`(Draft Guidance Document) Center for Drug Evaluation and
`Research and Center for Biologics Evaluation and Research (Dec.
`2002)
`Tr. transcript Dr. Candiotti direct 108:21-109:20, June 10, 2015 (5
`ml volume)
`January 16, 2002 Helsinn Press Release
`October 3, 2001 Helsinn Press Release
`April 10, 2001 Helsinn Press Release
`Kibbe, Handbook of Pharmaceutical Excipients, Citric Acid
`191-94 (3rd ed. 2000)
`U.S. Patent No. 9,066,980
`Serial No. 13/902,132 Official Action, Aug. 8, 2013
`Serial No. 13/902,182 Applicants’ Amendment and Response to
`Office Action, Oct. 9, 2013
`Declaration of Dr. Patrick P. DeLuca
`Dr. Patrick P. DeLuca curriculum vitae
`Patrick P. DeLuca and James C. Boylan, 5 Formulation of Small
`Volume Parenterals, 1 Pharmaceutical Dosage Forms:Parenteral
`Medications, 173(2nd ed. rev. expanded Marcel Dekker, Inc. 1992)
`Tr. transcript Dr. Amidon direct156:15-165:9, June 15, 2015
`(K.I.S.S. 5ml, Golden Rule, Ex.13 commercially viable)
`Brown et al., The Effectiveness of a Single Intravenous Dose of
`Ondansetron, Oncology 1992;49:273-278
`Helsinn Healthcare S.A. et al. v. Dr. Reddy’s Laboratories,
`Ltd. et al., Civil Action No. 12-2867-MLC (D.N.J. Feb. 19, 2015)
`Markman Order (Dkt.91), Feb. 19, 2015
`
`1043
`
`1044
`
`1045
`
`
`
`vii
`
`

`
`1047
`
`1048
`
`1049
`
`1050
`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`Exhibit # Reference
`1046
`Tr. transcript Dr. Amidon direct 106:2-107:18, June 16, 2015
`(EDTA citric acid)
`Tr. transcript Dr. Candiotti cross-examination 141:15-143:25,
`June 10, 2015 (human dose based on animals)
`Prosecution History of U.S. Patent No. 7,947,724 (U.S. Ser.
`No. 11/186311), Amend. Resp., Apr. 6, 2009
`Mikawa et al., Optimal Dose of Granisetron for Prophylaxis
`Against Postoperative Emesis After Gynecological Surgery, 85
`Anesth. Analg., 652-6 (1997) 
`Avis et al., 2 Parental Drug Administration: Routes, Precautions,
`Problems, Complications, and Drug Delivery Systems, 1
`Pharmaceutical Dosage Forms:Parenteral Medications 173(2nd ed.
`rev. expanded Marcel Dekker, Inc. 1992)
`Reproduction of Figure 5 of Eglen Exh.1011, at 863
`Reproduction of Figure 6a of Eglen Exh.1011, at 863
`Dose response curves for Chelly (Exh.1012) and Tang (Exh.1019)
`Approved KYTRIL Label, Aug. 16, 2002
`R.E. Leak and J.D. Woodford, Pharmaceutical Development of
`Ondansetron Injection, 25 (Suppl. 1) Eur. J. Cancer Clin.
`Oncol. 567-69 (1989)
`
`
`1051
`1052
`1053
`1054
`1055
`
`
`
`viii
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`

`
`
`
`Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc. request
`
`inter partes review of claims 22-27 and 30 of U.S. Patent No. 8,729,094 (“the
`
`‘094 Patent”) (Exh.1001).
`
`NOTICE OF LEAD AND BACKUP COUNSEL
`
`Backup Counsel:
`William L. Mentlik
`(Reg. No. 27,108)
`WMentlik.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6305
`Fax: 908.654.7866
`
`Thomas M. Palisi
`(Reg. No. 36,629)
`TPalisi.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6366
`Fax: 908.654.7866
`
`Maegan A. Fuller (Reg. No. 71,596)
`MFuller.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6324
`Fax: 908.654.7866
`
`
`Lead Counsel:
`Michael H. Teschner
`(Reg. No. 32,862)
`MTeschner.ipr@ldlkm.com
`Postal and Hand-Delivery Address
`600 South Avenue West
`Westfield, NJ 07090
`Telephone: 908.518.6313
`Fax: 908.654.7866
`
`
`
`
`
`
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`

`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`NOTICE OF EACH REAL-PARTY-IN-INTEREST
`The Real-Parties-In-Interest for this Petition are Requestor, Dr. Reddy’s
`
`Laboratories, Ltd. (“DRL LTD”) an Indian company, and Dr. Reddy’s
`
`Laboratories, Inc. (“DRL Inc.”) a U.S. company, and wholly owned subsidiary of
`
`DRL LTD. (collectively referred
`
`to herein as “DRL,” “Petitioner,” or
`
`“Requestor”).
`
`NOTICE OF RELATED MATTERS
`Patent Owner asserted the ‘094 Patent in a civil action filed in the United
`
`States District Court for the District of New Jersey (Civ. Action No. 14- 4274), on
`
`July 7, 2014 (“the Litigation”). (Exh.1006.) Patent Owner has also filed lawsuits
`
`against Petitioner involving other members of the ‘094 Patent’s immediate family.
`
`These include: Civ. Action No. 11-3962, filed July 8, 2011, alleging infringement
`
`of U.S. Patent Nos. 7,947,724 and 7,947,725 (Exhs.1002, 1003, respectively); Civ.
`
`Action No. 11-5579, filed September 23, 2011, alleging infringement of U.S. Pat.
`
`No. 7,960,424 (Exh.1004); Civ. Action No. 13-5815, filed December 27, 2013,
`
`alleging infringement of U.S. Patent Nos. 8,518,981; 8,598,218; and 8,598,219
`
`(Exh.1005); Civ. Action No. 12- 2867 filed May 11, 2012, alleging infringement of
`
`U.S. Pat. No. 7,947,724 (Exh.1002.) All of these cases are before The Honorable
`
`Judge Cooper in the U.S. District Court for the District of New Jersey.
`
`2
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`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`It is the undersigned’s understanding that the assertions of infringement of
`
`the ‘981 and ‘218 Patents were dismissed, and that some of the issues pled in the
`
`various complaints have been reorganized and in some cases consolidated. A trial
`
`was held before Judge Cooper on June 2-16, 2015, in Civ. Action No. 11-3962
`
`(“the Trial”) involving infringement and invalidity allegations for the ‘724, ‘725,
`
`‘424, and ‘219 Patents. (Exhs.1002-1005.) The undersigned is not a record counsel
`
`in any of these civil actions.
`
`Petitioner has filed three other IPR petitions concurrently on the same claims
`
`of
`
`the
`
`same patent under distinct
`
`theories bearing attorney docket
`
`nos. REDDY 7.1R-011, REDDY 7.1R-012, and REDDY 7.1R-013.
`
`NOTICE OF SERVICE INFORMATION
`Please address all correspondence to the lead and backup counsel at the
`
`address
`
`shown above. Petitioner also consents
`
`to electronic
`
`service
`
`by
`
`e-mail
`
`at: MTeschner.ipr@ldlkm.com, WMentlik.ipr@ldlkm.com,
`
`TPalisi.ipr@ldlkm.com, and MFuller.ipr@ldlkm.com.
`
`GROUNDS FOR STANDING
`Petitioner certifies that the patent for which review is sought is available for
`
`inter partes review, and that Petitioner is not barred or estopped from requesting an
`
`inter partes review on the grounds identified in the petition. This petition is being
`
`filed within one year of the filing of the Complaint in the Litigation, which
`
`3
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`

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`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`occurred on July 7, 2014. (Exh.1006.) The petition is thus timely under 35 U.S.C.
`
`§ 315(b). The fee for this petition has been paid. However, the U.S. Patent and
`
`Trademark Office is hereby authorized to charge Deposit Account No. 12-1095 for
`
`any fees that may be due and owing in connection with this petition.
`
`STATEMENT OF PRECISE RELIEF REQUESTED
`Petitioner requests that claims 22-27 and 30 of the ‘094 Patent be held
`
`unpatentable based on the following ground: obviousness over Eglen (Exh.1011)
`
`when taken in view of Chelly (Exh.1012), Gibson (Exh.1014), and the 2001
`
`Physicians’ Desk Reference (“PDR”) (Exhs.1015-1017). See 35 U.S.C. § 103.1
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`The Petition meets that threshold requirement of 35 U.S.C. § 314(a). All of
`
`the elements of claims 22-27 and 30 of the ‘094 Patent are taught, either expressly
`
`or inherently, in the prior art, or are obvious in view of the prior art, as explained
`
`below in the grounds of unpatentability. The reasons to combine the cited
`
`references, where applicable, are established under 35 U.S.C. § 103(a).
`
`
`1 Despite being based on a provisional application filed January 30, 2003, the
`
`‘094 Patent is governed by the changes to 35 U.S.C. §§ 102 and 103, as amended
`
`by the AIA for prior art purposes. (See Exh.1009, at 17-19.)
`
`4
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`
`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
`
`
`I.
`
`STATEMENT OF REASONS FOR RELIEF REQUESTED
`INTRODUCTION AND SUMMARY OF ARGUMENT
`The specification of
`the ‘094 Patent (Exh.1001), discusses, almost
`
`exclusively, stabilized formulations of the known antiemetic drug, palonosetron.
`
`Patent Owner argued in the specification that prior art intravenous (“IV”)
`
`formulations of palonosetron had a stability of less than one to two years, and that
`
`this was insufficient for “health authorities in various countries.” (Exh.1001 col.2
`
`ll.10-12.) Patent Owner allegedly solved that shelf life problem.
`
`The U.S. is not one of those countries requiring one to two years of shelf
`
`life. (Exhs.1023 ¶ 16; 1020.) More to the point, unlike its five relatives that only
`
`claim stabilized formulations (Exhs.1002-1005, 1037 (U.S. Pat. No. 9,066,980,
`
`which issued just days before the filing of this IPR)), the claims of the ‘094 Patent
`
`are solely directed to methods of treating chemotherapy induced nausea and
`
`vomiting (“CINV”) by administering palonosetron. And it is no less obvious to
`
`treat a patient’s CINV with a formulation having a 24-month shelf life than with a
`
`drug made yesterday and expiring tomorrow. (Exh.1021 ¶ 16.) Even Patent Owner,
`
`when given the opportunity by the Examiner, evaded arguing the impact of
`
`stability on the claimed method. (Exh.1009, at 17.)
`
`Independent claim 22 recites only a single method step ____ administering
`
`by IV a specific dose of palonosetron to a patient in need thereof, before starting
`
`5
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`Case IPR2015-01553
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-010
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`chemotherapy. The balance of its recitations are product or stability recitations,
`
`which are irrelevant to the claimed method and should be accorded little weight.
`
`Moreover, palonosetron is at least the fourth approved drug of its class in the U.S.,
`
`and its three FDA approved predecessors were all sold in low volume, sterile,
`
`single unit dose forms, for treating CINV by IV administration before
`
`chemotherapy, just as claimed. All had tonicity agents and most were buffered.
`
`One was even buffered and contained a chelating agent (citric acid) ____ just as
`
`claimed. And the agents used for tonicity and buffering were among the very most
`
`common of each category; indeed they were all used in at least one of the three
`
`commercial predecessors.
`
`Unlike many “new” drugs, the invention here was neither the discovery of
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`the drug itself nor its IV use to treat CINV ____ both were admittedly known for ten
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`years. (Exhs.1001 col.1 ll.35-62; 1010.) And Patent Owner made statements to the
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`press, all qualifying as prior art (Exhs.1033-1035), that IV palonosetron for
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`treating CINV had been a success in preclinical, Phase I, and Phase II trials. Also
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`in the prior art was Patent Owner’s announcement that a Phase III trial was nearing
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`completion and that submission of a new drug application to the FDA was
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`imminent. (Exh.1033.) Patent Owner would not have made such statements, and
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`the FDA would not have approved the Phase III trial, unless there was a reasonable
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`Attorney Docket No. REDDY 7.1R-010
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`expectation of safety and efficacy. Published studies provided an effective dosing
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`range and expressly indicated that palonosetron formulations in the effective range
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`were safe. (Exhs.1012, 1019.) That palonosetron would work was a foregone
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`conclusion.
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`With this information, and the general formulation knowledge of those of
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`ordinary skill at the time, nothing but routine experimentation would be required to
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`formulate a suitable parenteral palonosetron product, just like those already on the
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`market. Even arriving at a particular dose would be routine here, where the
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`preclinical and Phase II data were in agreement and suggested that virtually any
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`human dose above about 0.07 milligrams would work equally well. And while
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`Patent Owner has consistently argued nonobviousness of selecting the one claimed
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`dose, it has never argued that the claimed dose was better than any other.
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`II. THE CLAIMS UNDER CONSIDERATION
`22. A method for reducing the likelihood of cancer chemotherapy-induced
`nausea and vomiting, comprising intravenously administering to a human in need
`thereof a pharmaceutical single-use, unit-dose formulation comprising a 5 mL
`sterile aqueous isotonic solution buffered at a pH of about 5.0+0.5, said solution
`comprising: about 0.05 mg/mL palonosetron hydrochloride based on the weight of
`its free base; and a tonicifying effective amount of mannitol; wherein said solution
`optionally comprises one or a combination of a citrate buffer and a chelating agent,
`wherein said formulation is stable at 24 months when stored at room temperature,
`and wherein said intravenous administration to said human occurs before the start
`of the cancer chemotherapy.
`23. The method of claim 22, wherein said intravenous administration to
`said human occurs over a period of time of 10 to 60 seconds.
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`Attorney Docket No. REDDY 7.1R-010
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`24. The method of claim 22, wherein said intravenous administration
`reduces the likelihood of acute nausea and vomiting in said human.
`25. The method of claim 22, wherein said intravenous administration
`reduces the likelihood of delayed nausea and vomiting in said human.
`26. The method of claim 22, wherein said solution comprises a citrate
`buffer.
`27. The method of claim 22, wherein said solution comprises a chelating
`agent.
`,30. The method of claim 22, wherein said solution comprises from about
`10 mg/mL to about 80 mg/mL mannitol.
`III. THE SPECIFICATION AND
`PROSECUTION HISTORY OF THE ‘094 PATENT
`A. The Specification Of The ‘094 Patent
`The ‘094 Patent issued from U.S. Serial No. 13/902,132 on May 20, 2014,
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`based on a string of applications dating back to a January 30, 2003. In the
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`Summary of the Invention, Patent Owner argued that it made a series of
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`discoveries leading, allegedly, to “a surprisingly effective and versatile formulation
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`for the treatment and prevention of emesis using palonosetron.” (Exh.1001 col.2
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`ll.65-67.) “These formulations are shelf stable for periods greater than 24 months
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`at room
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`temperature and
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`thus can be stored without refrigeration, and
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`manufactured using non-aseptic, terminal sterilization processes.” (Id. col.3 ll.1-4.)
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`That series of alleged discoveries
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`included determining
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`that
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`low
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`concentrations of palonosetron can be used because palonosetron requires, in some
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`instances, only one-tenth the amount of other previously known compounds for
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`Attorney Docket No. REDDY 7.1R-010
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`treating emesis. (See id. col.3 ll.5-11.) Of course, in the Background of the
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`Invention, applicants conceded that palonosetron was already known to be “an
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`order of magnitude more potent than most existing 5-HT3 receptor antagonists.”
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`(Id. col.1 ll.58-61.) Using one-tenth as much of something 10x more potent is
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`hardly a surprise. Applicants also allegedly discovered that by adjusting the pH
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`and/or excipient concentration, it was possible to increase stability, and that the
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`addition of mannitol and a chelating agent enhanced stability as well. (See
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`generally id. col.3 ll.17-41.) But using such techniques was also well known.
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`The Detailed Description tracked the theme set by the Summary.
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`Examples 1-3 related to optimization studies, where “optimum” was based on the
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`impact of an excipient or condition on stability rather than impact on the patient.
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`(See generally id. col.7 ll.15-58.) The remaining examples recited specific
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`formulations and stability testing.
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`Given the nature of the claims of the ‘094 Patent, two aspects of the
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`specification are notable. First, it contains surprisingly little description of a
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`method of treatment. Aside from a brief discussion of the potential impact of lower
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`dosages of IV palonosetron on the length of the administration time (see id. col.5
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`ll.7-15), it contains no discussion of administration per se. And not even the few
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`Attorney Docket No. REDDY 7.1R-010
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`uses of the terms “method,” “process,” and “treating” were accompanied by a
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`description of a CINV treatment method.
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`Second,
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`the specification mentions only
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`the claimed 0.25mg dose
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`(5mlx0.05mg/ml). There is no discussion of a dosing range. And applicants never
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`suggested that this dose is better than any other.
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`B. The Prosecution History Of The ‘094 Patent
`U.S. Serial No. 13/902,132 was filed on May 24, 2013 as a continuation of
`
`its parent, U.S. Patent No. 8,598,219 (“the ‘219 Patent”). (Exh.1005.) The
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`‘219 Patent was a continuation-in-part filed only a day earlier. The application was
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`accompanied by a request for prioritized examination under 37 C.F.R. § 1.102(e).
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`A nonfinal rejection was mailed on August 8, 2013. (Exh.1038.) In pertinent part,
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`the claims directed to palonosetron formulations were rejected pursuant to 35
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`U.S.C. § 102(b) as being anticipated by Baroni et al., WO 2004/073714. Method
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`claims 12 and 15 were rejected as obvious over Baroni. (Id.)
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`On October 9, 2013, applicants filed a response and amendment. (See
`
`Exh.1039.) The product claims were canceled, and method claim 12 was amended
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`to include many of the product limitations found in the claims as issued. A number
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`of additional method claims were also added. Applicants argued that Baroni had an
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`effective filing date of February 18, 2003, pursuant to 35 U.S.C. § 102(a)(2) (id.
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`Attorney Docket No. REDDY 7.1R-010
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`at 10), and argued that the original claims 12-15 were fully supported by the
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`priority application and thus entitled to an effective filing date of January 30, 2003,
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`more than two weeks prior to Baroni.
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`The application was finally rejected on December 6, 2013. (See Exh.1008.)
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`The Examiner withdrew the prior rejections, and in their place rejected claims 12,
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`14-16, 18-24, 26-33, and 35-41 under pre-AIA 35 U.S.C. § 103(a) over Berger,
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`U.S. Patent No. 5,202,333 (Exh.1010), in view of a number of secondary
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`references. (Exh.1008, at 4). The Examiner noted that Berger taught a method of
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`treating and/or reducing chemotherapy induced nausea and vomiting with a
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`pharmaceutical solution comprising palonosetron in a pharmaceutically acceptable
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`carrier, in a single unit dosage, for intravenous use. The Examiner argued further
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`that Berger taught a concentration of palonosetron from about 0.000001%w to
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`10% w, and the use of citric acid, which the Examiner concluded was a chelating
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`agent. According to the Examiner, Berger made it obvious to formulate in any
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`volume from 1ml-100ml, and volume selection was a “matter of optimizations
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`within the purview of the skilled artisan.” (See generally id. at 4-5.)
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`The Examiner further noted that administration occurring before the start of
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`chemotherapy was found in the art, and that “wherein” clauses, such as the one
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`reciting the long-term stability, should not be given weight. (Id.) The Examiner
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`Attorney Docket No. REDDY 7.1R-010
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`also noted that Berger fails to teach a formulation comprising a specifically
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`claimed amount of EDTA, mannitol, and citric acid, and did not teach the pH. But
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`the Examiner then discussed the teachings of the secondary references in
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`combination to establish obviousness. A number of other rejections were
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`discussed, including double patenting.
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`Applicants responded on February 21, 2014 (see Exh.1009), noting the
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`patenting of other members of the same family including, inter alia, U.S. Patent
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`Nos. 7,947,724 (Exh.1002) and 8,598,219 (Exh.1005). While acknowledging that
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`the current application differed from those patents because it claimed a method,
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`applicants argued that the method claims included, directly or indirectly, many of
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`the same product features ____ including
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`the dose of palonosetron and
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`its
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`concentration. (Exh.1009, at 7.) Applicants argued that those features were not
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`considered obvious