Case IPR2015-
`Patent No. 8,729,094
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`
`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
`
`
`
`Patent No. 8,729,094
`Issue Date: May 20, 2014
`Title: LIQUID PHARMACEUTICAL FORMULATIONS OF PALONOSETRON
`____________________________
`
`Inter Partes Review No. Unassigned
`
`__________________________________________________________________
`
`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
`
`Helsinn Healthcare Exhibit 2074
`Dr. Reddy's Laboratories, Ltd., et al. v. Helsinn Healthcare S.A.
`Trial PGR2016-00007
`
`Page 1 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`TABLE OF CONTENTS
`
`
`
`Page
`
`TABLE OF AUTHORITIES ................................................................................... iii
`
`EXHIBIT LIST ........................................................................................................ iv
`
`STATEMENT OF REASONS FOR RELIEF REQUESTED .................................. 5
`
`I.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT .............................. 5
`
`II.
`
`THE CLAIMS UNDER CONSIDERATION ................................................. 6
`
`III. THE SPECIFICATION AND PROSECUTION HISTORY OF THE
`‘094 PATENT .................................................................................................. 7
`
`A. The Specification Of The ‘094 Patent ...................................................... 7
`
`B. The Prosecution History Of The ‘094 Patent ........................................... 9
`
`IV. CLAIM CONSTRUCTION ..........................................................................13
`
`A. Optionally ...............................................................................................13
`
`B. Acute And Delayed .................................................................................14
`
`C. Chelating Agent ......................................................................................15
`
`V.
`
`CLAIMS 22-27 AND 30 OF THE ‘094 PATENT ARE OBVIOUS OVER
`BERGER (EXH.1010) WHEN TAKEN IN VIEW OF CHELLY
`(EXH.1012), TANG (EXH.1019), AND LEAK (EXH.1055) ......................15
`
`A. The Level Of Ordinary Skill In The Art .................................................17
`
`B. Scope And Content Of The Prior Art .....................................................19
`
`1. The “Treatment” Limitations Of Claim 22 ......................................19
`
`a.
`
`b.
`
`Dosing Unit Conversions .......................................................19
`
`Berger .....................................................................................21
`
`
`
`i
`
`Page 2 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`c.
`
`d.
`
`e.
`
`Chelly .....................................................................................23
`
`Tang .......................................................................................24
`
`Berger, Chelly, And Tang Combined ....................................27
`
`2. Dose Adjustments ............................................................................30
`
`3. A POSA’s Use Of Data To Select A Dose ......................................31
`
`4. The Product Recitations Of The Claims ..........................................33
`
`C. Differences Between The Claims And The Prior Art.............................43
`
`D. Dependent Claims ...................................................................................50
`
`1. Claim 23 ...........................................................................................50
`
`2. Claim 24 ...........................................................................................50
`
`3. Claim 25 ...........................................................................................51
`
`4. Claim 26 ...........................................................................................52
`
`5. Claim 27 ...........................................................................................53
`
`6. Claim 30 ...........................................................................................54
`
`E. Claim Chart .............................................................................................54
`
`VI. CONCLUSION ..............................................................................................58
`
`
`
`
`
`
`
`ii
`
`Page 3 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`
`CASES
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`3M v. Chemque, Inc.,
`303 F.3d 1294 (Fed. Cir. 2002) .......................................................................... 17
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) ...................................................................... 44, 47
`
`Asyst Techs. Inc. v. Emtrak, Inc.,
`544 F.3d 1310 (Fed. Cir. 2008) .......................................................................... 45
`
`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) ............................................................................ 45
`
`In re Cuozzo Speed Techs., LLC,
`No. 2014-1301, Slip. Op. (Fed. Cir. Feb. 4, 2015) ............................................. 13
`
`Ericsson Inc. v. Intellectual Ventures II, LLC,
`IPR 2014-01412 (PTAB Mar. 18, 2015) ............................................................ 14
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ...................................................................... 16, 45
`
`Graham v. John Deere Co.,
`383 U.S. 1 (1966) ................................................................................................ 16
`
`KSR Int'l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ...................................................................................... 15, 16
`
`In re Merck & Co.,
`800 F.2d 1091 (Fed. Cir. 1986) .......................................................................... 31
`
`Mintz v. Dietz & Watson, Inc.,
`679 F.3d 1373 (Fed. Cir. 2012) ......................................................................... 17
`
`
`
`iii
`
`Page 4 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`Oracle Corp. v. Thought, Inc.,
`IPR 2014-00118 (PTAB Apr. 25, 2014) ............................................................ 14
`
`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) ............................................................... 16
`
`Univ. of Rochester v. G.D. Searle & Co.,
`249 F. Supp. 2d 216 (W.D.N.Y. 2033) ............................................................... 19
`
`Takeda Pharm. Co. v. Mylan Inc.,
`Case No. 13-4001, 2014 U.S. Dist. LEXIS 159527
` (N.D. Cal. Nov. 11, 2014).................................................................................. 19
`
` 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) .......................................... 18
`
`STATUTES, RULES & OTHER AUTHORITIES
`
`35 U.S.C. § 102 .................................................................................................passim
`
`35 U.S.C. § 103 ............................................................................................... 4, 10,16
`
`37 C.F.R. § 42.100(b) .............................................................................................. 13
`
`iv
`
`
`
`
`
`Page 5 of 68
`
`

`
`Case IPR2015-
`
`Petition for Inter Partes Review
`
`Attorney Docket No. REDDY 7.1R—013
`
`EXHIBIT LIST
`
`Exhibit#
`1001
`1002
`1003
`
`1005
`
`1008
`
`1009
`
`1010
`
`1011
`
`Page 6 of 68
`
`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: 1 1—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: 1 1-cv-05579-MLC-DEA filed 9/23/2011; Helsinn
`
`Healthcare S.A. and Roche Palo Alto LLC v. Dr. Reddy’s
`Laboratories, Ltd., Dr. Reda'y’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 Re'ection, Dec. 6, 2013
`
`Serial No. 13/902,132, Amendment After Final, Feb. 21, 2014
`
`U.S. Patent No. 5,202,333 (“Berer”)
`
`Eglen et al., Pharmacological characterization ofRS 25259-I97, a
`novel and selective 5-HT3 receptor antagonist, in vivo, 114 British
`J. Pharmacol. 860-66 (1985) (“E len”)
`
`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
`(Set. 1996) (“Chell ”)
`
`Page 6 of 68
`
`

`
`Case IPR2015-
`
`Petition for Inter Partes Review
`
`Attorney Docket No. REDDY 7.1R—013
`
`Exhibit#
`1013
`
`1017
`
`1018
`
`1020
`
`1021
`1022
`1023
`1024
`1025
`
`1026
`
`1027
`
`Gralla et al., Recommendations for the Use ofAntiemetics:
`Evidence—Based, Clinical Practice Guidelines, 17 J. Clin.
`
`Oncolo , No. 9, 2971-94 (Set. 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)
`
`ed.) Montvale, NJ: PDR Network
`
`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
`Antiemeticfor 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 Efiicacy 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.
`
`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 Proposalfor 5-HT3 Antagonists in the
`Prevention ofAcute Emesis Related to Highly Emetogenic
`Chemothera , su o ort care cancer (1998) 6:237—243 (“Gandara”)
`
`Tr. transcript Dr. Frame direct 109:2—110:15, 121:18—123:3,
`124220-128:4, June 8, 2015 (PONV to CINV)
`
`vi
`
`Page 7 of 68
`
`Page 7 of 68
`
`

`
`Case IPR2015-
`
`Petition for Inter Partes Review
`
`Attorney Docket No. REDDY 7.1R—013
`
`mm:
`1029
`Tr. transcript Dr. Candiotti direct 82:12-83:15, June 10, 2015
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1041
`
`1042
`
`1043
`
`1045
`
`(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
`
`Aril 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, Au. 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. 5111], Golden Rule, Ex.13 commercially viable)
`
`Ondansetron, Oncolo 1992;49:273-278
`Helsinn Healthcare S.A. et al. v. Dr. Reddy’s Laboratories,
`Ltd. et al., Civil Action No. l2—2867—MLC (D.N.J. Feb. 19, 2015)
`
`Markman Order (Dkt.91), Feb. 19, 2015
`
`Tr. transcript Dr. Amidon direct 10612-107: 18, June 16, 2015
`(EDTA citric acid)
`
`vii
`
`Page 8 of 68
`
`Page 8 of 68
`
`

`
`Case IPR2015-
`
`Petition for Inter Partes Review
`
`Attorney Docket No. REDDY 7.1R—013
`
`Exhibit#
`1047
`
`1048
`
`1051
`1052
`1053
`1054
`1055
`
`Tr. transcript Dr. Candiotti cross—examination 141: l5—143:25,
`June 10, 2015 (human dose based on animals)
`
`Prosecution History of U.S. Patent No. 7,947,724 (U.S. Ser.
`No. 1 1/ 18631 1), Amend. Resp., Apr. 6, 2009
`Mikawa et al., Optimal Dose of Granisetron for Prophylaxis
`Against Postoperative Emesis After Gynecological Surgery, 85
`Anesth. Anal ., 652-6 (1997)
`
`Avis et al., 2 Parental Drug Administration: Routes, Precautions,
`Problems, Complications, and Drug Delivery Systems, 1
`Pharmaceutical Dosage Forms:Parenteral Medications l73(2nd ed.
`rev. expanded Marcel Dekker, Inc. 1992)
`
`R.E. Leak and J.D. Woodford, Pharmaceutical Development of
`Ondansetron Injection, 25 (Suppl. 1) Eur. J. Cancer Clin.
`Oncol. 567-69 (1989)
`
`viii
`
`Page 9 of 68
`
`Page 9 of 68
`
`

`
`
`
`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
`
`
`
`
`
`
`
`
`
`Page 10 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`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
`
`Page 11 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`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 unique
`
`theories bearing attorney docket
`
`nos. REDDY 7.1R-010, REDDY 7.1R-011, and REDDY 7.1R-012.
`
`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
`
`Page 12 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`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: Claims 22-27 and 30 are obvious over
`
`Berger (Exh.1010), when taken in view of Chelly (Exh.1012), Tang (Exh.1019),
`
`and Leak (Exh.1055). See 35 U.S.C. § 103.1
`
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`
`This Petition meets the threshold requirement of 35 U.S.C. § 315(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 ground 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
`
`Page 13 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`STATEMENT OF REASONS FOR RELIEF REQUESTED
`
`I.
`
`INTRODUCTION AND SUMMARY OF ARGUMENT
`
`Palonosetron is a 5-HT3 receptor antagonist known for its ability to treat
`
`people undergoing chemotherapy to prevent chemotherapy-induced nausea and
`
`vomiting (CINV). Berger, U.S. Patent No. 5,202,333 (Exh.1010) is owned by
`
`Patent Owner and issued in 1993. Berger discloses palonosetron, IV formulations
`
`including palonosetron and its use for treating CINV. Indeed, Berger discloses a
`
`palonosetron IV formulation that even one of Patent Owner’s experts at Trial
`
`admitted was “potentially commercial viable.”
`
` Patent Owner has suggested that the formulation in Berger example 13 has a
`
`shelf life of less than 1-2 years. (Exh.1001 col.2 ll.10-12.) A US manufacturer,
`
`however, can pick any shelf life it can be justify (Exh. 1020), and it would want to
`
`maximize the shelf life of such a formulation. This would provide the motivation
`
`to seek out formulators, who would employ standard formulation procedures to
`
`design an improved parenteral drug product. They would use known, highly
`
`standardized procedures and well-established excipients. And one of their goals
`
`would be maximizing shelf life. As part of that standardized process, the relevant
`
`literature would be reviewed.
`
`That literature includes Leak (Exh.1055) which was not of record during the
`
`prosecution of the ‘094 Patent and is prior art under 35 U.S.C. § 102(a)(1). Leak
`
`5
`
`Page 14 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`discloses a parenteral formulation of ondansetron, another 5-HT3 receptor
`
`antagonist, which was stable for 3 years at room temperature. Moreover, its
`
`formulation is astonishingly similar to the formulation of Berger. Both were sterile,
`
`aqueous, isotonic solutions formulated for single use and single dose. Both
`
`included citric acid and both had pH in the mid 3’s.
`
`A POSA would reasonably expect that by using standard formulation
`
`procedures, procedures used in connection with virtually every IV product
`
`formulation to maximize storage stability, and knowing that a highly analogous
`
`product in the art was able to achieve a 3 year shelf life, she or he would be able to
`
`make simple adjustments to the formulation of Berger and realize longer shelf
`
`stability.
`
`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.
`
`6
`
`Page 15 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`
`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,
`
`based on a string of applications dating back to January 30, 2003. In the Summary
`
`of the Invention, Patent Owner argued that it made a series of discoveries leading,
`
`allegedly, to “a surprisingly effective and versatile formulation for the treatment
`
`and prevention of emesis using palonosetron.” (Exh. 1001 col.2 ll.65-67.) “These
`
`formulations are shelf stable for periods greater than 24 months at room
`
`temperature, and thus can be stored without refrigeration, and manufactured using
`
`non-aseptic, terminal sterilization processes.” (Id. col.3 ll.1-4.)
`
`That series of alleged discoveries
`
`included determining
`
`that
`
`low
`
`concentrations of palonosetron can be used because palonosetron requires, in some
`
`instances, only one-tenth the amount of other previously known compounds for
`
`7
`
`Page 16 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`treating emesis. (See id. col.3 ll.5-11.) Of course, in the Background of the
`
`Invention section, applicants conceded that palonosetron was already known to be
`
`“an order of magnitude more potent than most existing 5-HT3 receptor
`
`antagonists.” (Id. col.1 ll.58-61.) Using one-tenth as much of something 10x more
`
`potent is hardly a surprise. Applicants also allegedly discovered that by adjusting
`
`the pH and/or excipient concentration, it was possible to increase stability, and that
`
`the addition of mannitol and a chelating agent enhanced stability as well. (See
`
`generally id. col.3 ll.17-41.) But using such techniques was also well known.
`
`The Detailed Description section tracked the theme set by the Summary.
`
`Examples 1-3 related to optimization studies, where “optimum” was based on the
`
`impact of an excipient or condition on stability rather than impact on the patient.
`
`(See generally id. col.7 ll.15-58.) The remaining examples recited specific
`
`formulations and stability testing.
`
`Given the nature of the claims of the ‘094 Patent, two aspects of the
`
`specification are curious. First, it contains surprisingly little description of a
`
`method of treatment. Aside from a brief discussion of the potential impact of lower
`
`dosages of IV palonosetron on the length of the administration time (see id. col.5
`
`ll.7-15), it contains no discussion of administration per se. And not even the few
`
`8
`
`Page 17 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`uses of the terms “method,” “process,” and “treating” were accompanied by a
`
`description of a CINV treatment method.
`
`Second,
`
`the
`
`specification mentions
`
`only
`
`the
`
`one
`
`dose
`
`(5mlx0.05mg/ml=0.25mg), with no discussion of a dosing range. It never suggests
`
`that this dose is particularly unexpectedly better than any other.
`
`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
`
`‘219 Patent was a continuation-in-part filed only a day earlier. The application was
`
`accompanied by a request for prioritized examination under 37 C.F.R. § 1.102(e).
`
`A nonfinal rejection was mailed on August 8, 2013. (Exh.1038.) In pertinent part,
`
`the claims directed to palonosetron formulations were rejected pursuant to 35
`
`U.S.C. § 102(b) as being anticipated by Baroni et al., WO 2004/073714. Method
`
`claims 12 and 15 were rejected as obvious over Baroni. (Id.)
`
`On October 9, 2013, applicants filed a response and amendment. (See
`
`Exh.1039.) The product claims were canceled, and method claim 12 was amended
`
`to include many of the product limitations found in the claims as issued. A number
`
`of additional method claims were also added. Applicants argued that Baroni had an
`
`effective filing date of February 18, 2003, pursuant to 35 U.S.C. § 102(a)(2) (id.
`
`9
`
`Page 18 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`at 10), and argued that the original claims 12-15 were fully supported by the
`
`priority application and thus entitled to an effective filing date of January 30, 2003,
`
`more than two weeks prior to Baroni.
`
`The application was finally rejected on December 6, 2013. (See Exh.1008.)
`
`The Examiner withdrew the prior rejections, and in their place rejected claims 12,
`
`14-16, 18-24, 26-33, and 35-41 under pre-AIA 35 U.S.C. § 103(a) over Berger,
`
`U.S. Patent No. 5,202,333 (Exh.1010), in view of a number of secondary
`
`references. (Exh.1008, at 4.) The Examiner noted that Berger taught a method of
`
`treating and/or reducing chemotherapy induced nausea and vomiting with a
`
`pharmaceutical solution comprising palonosetron in a pharmaceutically acceptable
`
`carrier, in a single unit dosage, for intravenous use. The Examiner argued further
`
`that Berger taught a concentration of palonosetron from about 0.000001%w to
`
`10% w, and the use of citric acid, which the Examiner concluded was a chelating
`
`agent. According to the Examiner, Berger made it obvious to formulate in any
`
`volume from 1ml-100ml, and volume selection was a “matter of optimizations
`
`within the purview of the skilled artisan.” (See generally id. at 4-5.)
`
`The Examiner further noted that administration occurring before the start of
`
`chemotherapy was found in the art, and that “wherein” clauses, such as the one
`
`reciting the long term stability, should not be given weight. (Id.) The Examiner
`
`10
`
`Page 19 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`also noted that Berger fails to teach a formulation comprising a specifically
`
`claimed amount of EDTA, mannitol, and citric acid, and did not teach the pH. But
`
`the Examiner then discussed the teachings of the secondary references in
`
`combination to establish obviousness. A number of other rejections were
`
`discussed, including double patenting.
`
`Applicants responded on February 21, 2014 (see Exh.1009), noting the
`
`patenting of other members of the same family including, inter alia, U.S. Patent
`
`Nos. 7,947,724 (Exh.1002) and 8,598,219 (Exh.1005). While acknowledging that
`
`the current application differed from those patents because it claims a method,
`
`applicants argued that the method claims included, directly or indirectly, many of
`
`the same product features ____ including the dose of palonosetron and its
`
`concentration. (Exh.1009, at 7.) Applicants argued that those features were not
`
`considered obvious during the prosecution of related patents and implied that those
`
`features should support patentability of the methods claimed as well. (Id.)
`
`In addressing the primary rejection of the claims based on Berger
`
`(Exh.1010), applicants argued that the office action did not account for the
`
`invention as a whole because it did not properly address the dose and concentration
`
`features of the claims. (Exh.1009, at 8.) They also pointed to the Examiner’s
`
`consideration of Tang (Exh.1019) during the prosecution of the ‘094 Patent’s
`
`11
`
`Page 20 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`parent, the ‘219 Patent (Exh.1005). Patentee argued that the Examiner in that case
`
`had recognized that Tang taught that palonosetron was effective only at higher
`
`doses than that claimed, i.e., 30µg/kg, which translates to 2.1mg, when an average
`
`weight 70kg patient is used to calculate dose. (Exh.1009, at 8-9.)
`
`Applicants then discussed the Berger reference, specifically noting that it
`
`taught only broad ranges of concentration and only exemplified the use of
`
`10-100mg/ml, which was, allegedly, 200-2000 times greater than the 0.05mg/ml
`
`concentration claimed. It also argued that Berger disclosed a broad range of
`
`palonosetron doses, ranging from 70ng/day to 70mg/day, preferably 700ng/day to
`
`7.0mg/day, based on a 70kg person. “Thus, Berger describes a general dose range
`
`spanning six orders of magnitude . . . and subsequently leads the worker of
`
`ordinary skill to a preferred dose range that spans four orders of magnitude . . . and
`
`eventually to a dose range of 10-100mg/day in Example 13.” (Id. at 10.)
`
`It is worth noting that Example 13 of Berger does not suggest any particular
`
`dose, let alone a dose of 10-100mg per day. Applicants appear to have focused on
`
`the mere fact of a difference between the art and the one claimed dose, and not on
`
`the impact of that difference, if any. A notice of allowance subsequently issued on
`
`March 25, 2014, without further explanation.
`
`12
`
`Page 21 of 68
`
`

`
`Case IPR2015-
`Petition for Inter Partes Review
`Attorney Docket No. REDDY 7.1R-013
`
`IV. CLAIM CONSTRUCTION
`
`In inter partes review, a claim term is given its “broadest reasonable
`
`construction in light of the specification.” See 37 C.F.R. § 42.100(b); see also
`
`In re Cuozzo Speed Techs., 778 F.3d 1271 (Fed. Cir. 2015), reh’g requested
`
`(Mar. 23, 2015).
`
`A. Optionally
`
`Claim 22 “optionally” comprises one