USOO8729094B2
`
`(12) United States Patent
`Calderari et a].
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`US 8,729,094 B2
`*May 20, 2014
`
`(54) LIQUID PHARMACEUTICAL
`FORMULATIONS OF PALONOSETRON
`
`5,011,846 A
`5,034,398 A
`5,202,333 A
`
`4/1991 Gittos et a1.
`7/ 1991 K1118
`4/1993 Berger et a1.
`
`(71) Applicants:Helsinn Healthcare SA, Lugano (CH); Roche Palo Alto LLC, Palo Alto, CA
`
`(US); Simone Macciocchi, Melide (CH);
`Giulio Macciocchi, Breganzona (CH)
`(72) Inventors: Giorgio Calderari, Rancate (CH);
`Daniele 13011211160, CasalZuignO (1T);
`Roberta Carmella, Varese (IT); Alberto
`Macciocchi, Melide (CH); Andrew
`322115: gisgbgomas
`’
`’
`’
`Kathleen M Lee, P2110 A110, CA (Us)
`
`-
`
`.
`
`(73) Assignees: Helsinn Healthcare SA,
`Pambio-Noranco (CH); Roche Palo Alto
`LLC’ palo Alto, CA (Us)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`This patent is subject to a terminal dis
`claimer.
`
`(21) App1_ NO; 13/902432
`
`(22) Filed_
`
`~
`
`May 24 2013
`
`1
`
`(65)
`
`Prior Publication Data
`
`US 2013/0261 150 Al
`
`Oct. 3, 2013
`
`.
`.
`Related U's' Apphcatlon Data
`(63) Continuation of application No. 13/901,437, ?led on
`May 23, 2013, now Pat. No. 8,598,219, which is a
`continuation_in_part Of application NO_ 13 /()87,01 2’
`?led OHAPL 14 2011 HOW Pat NO_ 8 518 981 which
`is a continuation of application No. 11/186,311, ?led
`on Jul' 21 2005 HOW Pat NO' 7 947 724 which is a
`continuation Ofa’ lication NO P’CT “5P2 0’0 4 /000888
`?l d
`J
`30 123804
`'
`’
`6 on an'
`’
`'
`(60) Provisional application NO_ 60/444,351, ?led on Jan
`30, 2003.
`(51) Int Cl
`A 61K 47/00
`(52) US. Cl.
`USPC ........................................................ .. 514/296
`(58) Field of Classi?cation Search
`USPC ........................................................ .. 514/296
`See application ?le for complete search history.
`
`(2006.01)
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`9/1987 Coates et a1.
`4,695,578 A
`6/1988 Tyers et a1.
`4,753,789 A
`4,886,808 A 12/1989 King
`4,906,755 A
`3/1990 Gittos
`4,929,632 A
`5/1990 Tyers et a1.
`4,937,247 A
`6/1990 King
`
`3:5: 2; 9/1994 Collin
`i 533443653 A
`
`
`5,578,628 A 11/1996 Tyers et a1.
`5,578,632 A 11/1996 Tyer§ et 31~
`5,622,720 A
`4/1997 Collin _
`2
`231‘
`5,955,488 A
`9/1999 Winterborn
`6,063,802 A
`5/2000 Winterborn
`2,
`Q1
`gunfgyer ef al.
`6,287,592 B1
`9/2001 Dickinson
`9/2001 James
`6,294,548 B1
`6,699,852 B2
`3/2004 Robichaud
`7,109,339 B2
`9/2006 Lee et a1.
`7,947,724 B2
`5/2011 Calderari et a1.
`gaigemr! e; ai'
`8/2013 Calderari et a1.
`8,518,981 B2
`9/2001 James
`2001/0020029 A1
`5/2003 Bugger, 111
`2003/0095926 A1
`2004/0147510 A1* 7/2004 Landau et a1. .............. .. 514/218
`
`,
`
`,
`
`ast1 0 eta .
`
`,
`
`,
`
`a erar1 e a .
`
`FOREIGN PATENT DOCUMENTS
`
`0 512 400 A1
`EP
`WO-03100091
`WO
`W0 WO-2004045615
`WO WO-2004067005
`WO WO-20047037l4
`
`4/1992
`12/2003
`6/2004
`8/2004
`9/2004
`
`OTHER PUBLICATIONS
`
`CDER (Clinical Pharmacology and Biopharmaceutics Review (Sep.
`2002).*
`Perez et a1. (cancer J. Sci Am. (1998) 4(1):52.*
`R. M. Eglen et al., “Pharmacological characterization of RS 25259
`197, a novel and selective 5-HT3 receptor antagonist, in ViVO,” Br J
`Pharmamlogy1141860-866(1995)~
`Chelly, Jacques et al., Oral RS-25259 Prevents Postoperative Nausea
`and Vomiting Following Laparoscopic Surgery, Anesthesiology,
`1996’ vol' 85’ NO' 3A’ p' A21'
`_
`_
`_
`_
`Sorbe, Bengt, 5-HT-3 Receptor Antagonists as Antiemetlc Agents in
`Cancer Chemotherapy, extracted from Expert Op1n10n 0n Investlga
`{10113.1 Drugs, 1996, vol. 5 N0. 4, pp. 389-407.
`Gaster, Laramie M. and King, Frank D., Serotonin 5-HT3 and 5-HT4
`Receptor Antagonists, extracted from Medicinal Research Reviews,
`1997 vol. 17, N0. 2, pp. 163-214.
`
`(Continued)
`
`Primary Examiner * Shirley V Gembeh
`(74) Attorney! Agent] or Firm i Clark 6 Sullivan;
`Troutman Sanders LLP
`
`(57)
`
`ABSTRACT
`
`The present invention relates to shelf-stable liquid formula
`tions of palonosetron for reducing chemotherapy and radio
`therapy induced emesis with palonosetron. The formulations
`are particularly useful in the preparation of intravenous and
`oral liquid medicaments.
`Dr. Reddy’s Laboratories, Ltd., et al.
`v.
`Helsinn Healthcare S.A., et al.
`30 Claims, No Drawings
`U.S. Patent No. 9,(cid:20)(cid:26)(cid:22),(cid:28)(cid:23)(cid:21)
`Reddy Exhibit 1051
`
`

`
`USOO8729094B2
`
`(12) United States Patent
`Calderari et a].
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`US 8,729,094 B2
`*May 20, 2014
`
`(54) LIQUID PHARMACEUTICAL
`FORMULATIONS OF PALONOSETRON
`
`5,011,846 A
`5,034,398 A
`5,202,333 A
`
`4/1991 Gittos et a1.
`7/ 1991 K1118
`4/1993 Berger et a1.
`
`(71) Applicants:Helsinn Healthcare SA, Lugano (CH); Roche Palo Alto LLC, Palo Alto, CA
`
`(US); Simone Macciocchi, Melide (CH);
`Giulio Macciocchi, Breganzona (CH)
`(72) Inventors: Giorgio Calderari, Rancate (CH);
`Daniele 13011211160, CasalZuignO (1T);
`Roberta Carmella, Varese (IT); Alberto
`Macciocchi, Melide (CH); Andrew
`322115: gisgbgomas
`’
`’
`’
`Kathleen M Lee, P2110 A110, CA (Us)
`
`-
`
`.
`
`(73) Assignees: Helsinn Healthcare SA,
`Pambio-Noranco (CH); Roche Palo Alto
`LLC’ palo Alto, CA (Us)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`This patent is subject to a terminal dis
`claimer.
`
`(21) App1_ NO; 13/902432
`
`(22) Filed_
`
`~
`
`May 24 2013
`
`1
`
`(65)
`
`Prior Publication Data
`
`US 2013/0261 150 Al
`
`Oct. 3, 2013
`
`.
`.
`Related U's' Apphcatlon Data
`(63) Continuation of application No. 13/901,437, ?led on
`May 23, 2013, now Pat. No. 8,598,219, which is a
`continuation_in_part Of application NO_ 13 /()87,01 2’
`?led OHAPL 14 2011 HOW Pat NO_ 8 518 981 which
`is a continuation of application No. 11/186,311, ?led
`on Jul' 21 2005 HOW Pat NO' 7 947 724 which is a
`continuation Ofa’ lication NO P’CT “5P2 0’0 4 /000888
`?l d
`J
`30 123804
`'
`’
`6 on an'
`’
`'
`(60) Provisional application NO_ 60/444,351, ?led on Jan
`30, 2003.
`(51) Int Cl
`A 61K 47/00
`(52) US. Cl.
`USPC ........................................................ .. 514/296
`(58) Field of Classi?cation Search
`USPC ........................................................ .. 514/296
`See application ?le for complete search history.
`
`(2006.01)
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`9/1987 Coates et a1.
`4,695,578 A
`6/1988 Tyers et a1.
`4,753,789 A
`4,886,808 A 12/1989 King
`4,906,755 A
`3/1990 Gittos
`4,929,632 A
`5/1990 Tyers et a1.
`4,937,247 A
`6/1990 King
`
`3:5: 2; 9/1994 Collin
`i 533443653 A
`
`
`5,578,628 A 11/1996 Tyers et a1.
`5,578,632 A 11/1996 Tyer§ et 31~
`5,622,720 A
`4/1997 Collin _
`2
`231‘
`5,955,488 A
`9/1999 Winterborn
`6,063,802 A
`5/2000 Winterborn
`2,
`Q1
`gunfgyer ef al.
`6,287,592 B1
`9/2001 Dickinson
`9/2001 James
`6,294,548 B1
`6,699,852 B2
`3/2004 Robichaud
`7,109,339 B2
`9/2006 Lee et a1.
`7,947,724 B2
`5/2011 Calderari et a1.
`gaigemr! e; ai'
`8/2013 Calderari et a1.
`8,518,981 B2
`9/2001 James
`2001/0020029 A1
`5/2003 Bugger, 111
`2003/0095926 A1
`2004/0147510 A1* 7/2004 Landau et a1. .............. .. 514/218
`
`,
`
`,
`
`ast1 0 eta .
`
`,
`
`,
`
`a erar1 e a .
`
`FOREIGN PATENT DOCUMENTS
`
`0 512 400 A1
`EP
`WO-03100091
`WO
`W0 WO-2004045615
`WO WO-2004067005
`WO WO-20047037l4
`
`4/1992
`12/2003
`6/2004
`8/2004
`9/2004
`
`OTHER PUBLICATIONS
`
`CDER (Clinical Pharmacology and Biopharmaceutics Review (Sep.
`2002).*
`Perez et a1. (cancer J. Sci Am. (1998) 4(1):52.*
`R. M. Eglen et al., “Pharmacological characterization of RS 25259
`197, a novel and selective 5-HT3 receptor antagonist, in ViVO,” Br J
`Pharmamlogy1141860-866(1995)~
`Chelly, Jacques et al., Oral RS-25259 Prevents Postoperative Nausea
`and Vomiting Following Laparoscopic Surgery, Anesthesiology,
`1996’ vol' 85’ NO' 3A’ p' A21'
`_
`_
`_
`_
`Sorbe, Bengt, 5-HT-3 Receptor Antagonists as Antiemetlc Agents in
`Cancer Chemotherapy, extracted from Expert Op1n10n 0n Investlga
`{10113.1 Drugs, 1996, vol. 5 N0. 4, pp. 389-407.
`Gaster, Laramie M. and King, Frank D., Serotonin 5-HT3 and 5-HT4
`Receptor Antagonists, extracted from Medicinal Research Reviews,
`1997 vol. 17, N0. 2, pp. 163-214.
`
`(Continued)
`
`Primary Examiner * Shirley V Gembeh
`(74) Attorney! Agent] or Firm i Clark 6 Sullivan;
`Troutman Sanders LLP
`
`(57)
`
`ABSTRACT
`
`The present invention relates to shelf-stable liquid formula
`tions of palonosetron for reducing chemotherapy and radio
`therapy induced emesis with palonosetron. The formulations
`are particularly useful in the preparation of intravenous and
`oral liquid medicaments.
`
`30 Claims, No Drawings
`
`Exh. 1051
`
`

`
`US 8,729,094 B2
`Page 2
`
`(56)
`
`References Cited
`
`OTHER PUBLICATIONS
`
`Tang, Jun et al., “Ef?cacy of RS-25259, a Novel 5-HT3 Antagonist,
`in the Prevention of Postoperative Nausea and Vomiting after Maj or
`Gynecologic Surgery,”Anesthesiology, 1997, vol. 85, No. 3 suppl. p.
`A329.
`Tang, Jun et al., The Ef?cacy ofRS-25259, a Long-Acting Selective
`5-HT3 Receptor Antagonist, for Preventing Postoperative Nausea
`and Vomiting After Hysterectomy Procedures, Anesthesia and Anal
`gesia, 1998, vol. 87, pp. 462-467.
`Adis R&D Pro?le, Palonosetron RS 25259 197, Drugs in R&D, Oct.
`1999, vol. 2, No. 4, pp. 251-252.
`Piraccini Gaia et al., An Interesting 5-HT3 Receptor Antagonist
`Antiemetic for Patients Undergoing Chemotheraphy-based Condi
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`Stacher, Georg, Palonosetron Helsinn, Current Opinion in Investiga
`tional Drugs. Oct. 2002, vol. 3, No. 10, pp. 1502-1507.
`Navari, Rudolph M., Pathogenesis-Based Treatment of Chemo
`therapy-Induced Nausea and VomitingiTwo New Agents, Journal
`of Supportive Oncology, 2003, vol. 1(2), pp. 89-103.
`Chaitow, 1990, 3 pages.
`Opposition Brief ?led by Dr. Reddy’s Laboratories (UK) Limited,
`opposition to European Patent No. 1601359 B1 dated Jul. 7, 2009.
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`12915 (Won C. M. et al., International Journal of Pharmaceutics 121.
`95-105 (1995).
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`patients receiving highly emetogenic chemotherapy. Piraccini et al.,
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`pain and tissue damage associated with parenteral products. LarryA.
`Gatlin and Carol A. Brister Gatlin, from Injectable Drug Develop
`ment: Techniques to Reduce Pain and Irritation (Edited by Pramod K.
`Gupta and Gayle A. Brazeau; published by Informa Health Care)
`1999; ISBN 1574910957, 9781574910957, p. 401-421.
`Parenteral Dosage Forms. Joanne Broadhead, from Part lliEarly
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`Opposition Brief ?led by Tecnimede Sociedade Tecnico-Medicinal
`SA. in opposition to European Patent No. 1601359 B1, Jul. 8,2009.
`Response brief ?led by Helsinn Healthcare S.A. dated Jul. 13, 2007,
`in response to the communication pursuant to Art. 96(2) EPC of Jan.
`3, 2007 regarding Serial No. 04 706 657.6-2123.
`European Patent Of?ce of?cial communication dated Jul. 19, 2006,
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`Response of Helsinn Healthcare S.A. dated Nov. 29, 2006, regarding
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`1986, third edition, pp. 652-784.
`Declaration of Valentino J. Stella, Ph.D. dated Sep. 19, 2007.
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`Response of Helsinn Healthcare to opposition of EP Serial No. 04
`706 657.6, dated Feb. 11,2010.
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`Annex 2 to Response of Helsinn Healthcare to Opposition of EP
`Serial No. 04 706 657.6 dated Feb. 11,2010.
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`May 24, 2011 Para. IV notice from Teva Pharmaceuticals re ’724 and
`’725 patents.
`May 24, 2011 Para. IV notice from Sandoz re ’724 and ’725 patents.
`May 24, 2011 Para. IV notice from Dr. Reddy’s re ’724 and ’725
`patents.
`Aug. 9, 2011 Para. IV notice from Dr. Reddy’s re ’424 patent.
`Aug. 19, 2011 Para. IV notice from Teva Pharmaceuticals re ’424
`patent.
`Sep. 22, 2011 Para. IV notice from Sandoz re ’724, ’725 and ’424
`patents.
`Jul. 8, 2011 Complaint for patent infringement (D. N.J. case No.
`1 1-03962).
`Sep. 23, 2011 Complaint for patent infringement (D. N.J. case No.
`1 1-5579).
`Aug. 31, 2011 Answer and counterclaim of Dr. Reddy’s Laborato
`ries, Ltd. and Dr. Reddy’s Laboratories, Inc. (D. N.J. case No.
`1 1-03962).
`Sep. 13, 2011 Sandoz Inc. ’s answer to complaint for patent infringe
`ment and counterclaims (D. N.J. case No. 11-03962).
`Sep. 13, 2011 Teva Pharmaceuticals USA, Inc. and Teva Pharmaceu
`tical Industries Ltd.’s answer (D. N.J. case No. 11-03962).
`Oct. 5, 2011 Plaintiffs reply to answer and counterclaim of Dr.
`Reddy’s Laboratories, Ltd. and Dr. Reddy Laboratories, Inc. (D. N.J.
`case No. 11-03962).
`Oct. 21, 2011 Plaintiffs reply to Sandoz Inc.’s answer to complaint
`for patent infringement and counterclaims (D. N.J. case No.
`1 1-03962).
`Oct. 24, 201 1 Answer and counterclaim of Dr. Reddy’s Laboratories,
`Ltd. and Dr. Reddy’s Laboratories, Inc. (D. N.J. case No. 11-5579).
`Oct. 24, 2011 Sandoz Inc. ’s answer to complaint for patent infringe
`ment and counterclaims (D. N.J. case No. 11-5579).
`Oct. 27, 2011 Order consolidating the two cases (D. N.J. case No.
`1 1-5579).
`Nov. 17, 2011 Plaintiffs’ reply to answer and counterclaim of Dr.
`Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc. (D.
`N.J. case No. 11-03962).
`Nov. 17, 2011 Plaintiffs’ reply to Sandoz Inc.’s answer to complaint
`for patent infringement and counterclaims (D. N.J. case No.
`1 1-03962).
`
`Exh. 1051
`
`

`
`US 8,729,094 B2
`Page 3
`
`(56)
`
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`May 21, 2012 Plaintiffs’ opening claim construction brief (including
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`Jul. 20, 2012 Defendants’ responsive claim construction brief
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`Jul. 20, 2012 Plaintiffs’ responsive claim construction brief (includ
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`Sep. 7, 2012 Court transcript from Sep. 7, 2012 Markman hearing and
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`Dec. 1, 2011 Teva Pharmaceuticals USA, Inc. and Teva Pharmaceu
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`Sep. 25, 2012 Sandoz Inc.’s ?rst amended invalidity contentions
`pursuant to L. Pat. R. 3.6(c) (D. N.J. case No. 11-03962).
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`Injectable Drugs, pp. XI-XVI (ASHP 7th ed. 1992).
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`tion to Commercial Dosage Form, Ch. 9, pp. 331-354 (Gibson ed.,
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`ed. 2001).
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`pp. 683-688 (ASHP 7th ed. 1992).
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`KYTRIL® (granisetron HCI) South African Prescribing Information
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