In re Application of:
`
`Calderari, et al.
`
`Serial No.:
`
`11/186,311
`
`Filing Date:
`
`July 21, 2005
`
`)
`
`Title: LIQUID PHARMACEUTICAL
`FORMULATIONS OF
`PALONOSETRON
`
`)
`)
`)
`)
`)
`)
`
`)
`)
`)
`)
`
`Art Unit: 1614
`
`Examiner: Gembeh, Shirley V.
`
`STATUTORY DECLARATION OF DANIELE BONADEO, M. Chem. Pharm.
`37 C.F.R. §§ 131 and 132
`
`Commissioner for Patents
`P .0. Box 1450
`Alexandria, VA 22313-1450
`
`3)
`
`I, Daniele Bonadeo, hereby give this declaration under 37 C.F.R. §§ 131 and 132:
`1)
`My name is Daniele Bonadeo.
`I make this declaration based on my own personal knowledge, information, and belief. I
`2)
`am competent to testify concerning the matters set forth herein.
`I am Deputy Director, Head of Corporate Technical Affairs, Manufacturing Operations,
`for Helsinn Healthcare SA ("Helsinn"), the assignee of the above-referenced patent
`application.
`I am also an inventor for this application.
`This patent application is based on the discovery of liquid formulations of palonosetron
`hydrochloride with improved stability. The formulations can be stored for prolonged
`
`4)
`5)
`
`I hereby certify that this correspondence is being deposited with the United States Postal Service as first class mail
`addressed to: Commissioner for Patents, P. 0. Box 1450, Alexandria, VA 22313-1450, on February 1-C., 200'~
`
`Clark G. Sullivan, Reg. No. 36,942
`
`Dr. Reddy’s Laboratories, Ltd., et al.
`v.
`Helsinn Healthcare S.A., et al.
`U.S. Patent No. 9,(cid:20)(cid:26)(cid:22),(cid:28)(cid:23)(cid:21)
`Reddy Exhibit 1032
`
`Exh. 1032
`
`

`
`Serial No. 11/186,311
`Declaration ofDaniele Bonadeo
`Page2 of4
`
`periods of time in a variety of conditions without significant degradation or loss of
`potency, and thus are considered pharmaceutically stable.
`The formulations were developed by myself and others at Helsinn in the late 1990s, and
`were completed sometime before March 24, 1999.
`We filed U.S.S.N. 60/444,351, which was our first patent application based on these
`formulations, on January 30, 2003. We filed PCT application No. PCT/EP04/000888 on
`January 30, 2004, claiming priority to the '351 application. We filed U.S.S.N.
`11/186,311 on July 21,2005, claiming priority to the US '351 and PCT '888 applications.
`Finally, we filed three continuation applications -- U.S.S.N. 11/388,268 (the '268
`application), U.S.S.N. 111388,269 (the '269 application), and U.S.S.N. 11/388,270 (the
`'270 application), on March 4, 2006, claiming priority to the US '311 application, the US
`'351 application, and the PCT '888 application.
`Each of the foregoing applications contains the following example of an injectable
`formulation of palonosetron hydrochloride:
`
`6)
`
`7)
`
`8)
`
`EXAMPLE 4: FORMULATION [
`
`Ingredient
`Palonosetron Hydrochloride
`Mannitol
`EDTA
`Trisodium citrate
`Citric acid
`WFJ
`hydroxide
`solution
`Sodium
`hydrochloric acid solution
`
`and/or
`
`me/mL
`0.05
`41.5
`0.5
`3.7
`1.56
`1.0
`pH5.0±0.5
`
`9)
`1 0)
`
`For ease of reference, I will refer to this formulation as the Example 4 formulation.
`The Example 4 formulation was developed sometime before March 24, 1999, by myself
`and others at Helsinn Healthcare, and transmitted to a contract manufacturer for Helsinn,
`Oread Laboratories in Palo Alto California ("Oread"), for the production of commercial
`scale batches of palonosetron hydrochloride.
`
`Exh. 1032
`
`

`
`Serial No. 11/186,311
`Declaration ofDaniele Bonadeo
`Page 3 of4
`
`11)
`
`12)
`
`13)
`
`14)
`
`15)
`
`16)
`
`1 7)
`
`A copy of the master batch record developed by Oread for the formulation is contained in
`Exhibit A hereto.
`The master batch record describes the Example 4 formulation on page 2 of22. As can be
`seen, the batch record has an effective date of March 24, 1999, and thus makes clear that
`we had developed the formulation before this date.
`I am familiar with the work of Macciocchi et al. that is described in WO 2004/045615
`(the "Macciocchi application"), and the work of Baroni et al. that is described in WO
`2004/073714 (the "Baroni application"). With the exception of Dr. Macciocchi, who
`recently passed away, the inventors for those patent applications are close colleagues of
`mine who also work at Helsinn or, in the case of Dr. Baroni, recently retired from
`Helsinn.
`The Macciocchi and Baroni PCT applications were filed on November 6, 2003 and
`February 18, 2004, respectively, which is more than four years after we first invented the
`Example 4 formulation.
`At least some of the clinical studies described in the Macciocchi and Baroni applications
`used the Example 4 formulation.
`Any description in the Macciocchi and Baroni applications of palonosetron formulations
`having a pH between 4 and 6, palonosetron concentrations between 0.01 and 5.0 mg/ml,
`or the use of mannitol or a chelating agent in liquid palonosetron formulations, was
`derived from the Example 4 formulation that we presented to Drs. Macciocchi and Baroni
`for use by them in their clinical programs.
`All of the formulation development work described in the foregoing paragraphs was
`performed in Switzerland, which to my knowledge has been a member of the World
`Trade Organization (WTO) since July 1, 1995, and the United States.
`
`I declare that all statements made herein of my own knowledge are true and that all
`statements made on information and belief are believed to be true, further, that these statements
`were made with the knowledge that willful false statements and the like so made are punishable
`
`Exh. 1032
`
`

`
`by fine or imprisonment, or both, under Section 1001 of Title 18 of the United States Code. I
`declare under penalty of perjury that the foregoing is true and correct.
`
`Serial No. 111186,311
`Declaration ofDaniele Bonadeo
`Page4 of4
`
`Dated: February 13, 2007
`
`Daniele Bonadeo
`
`Exh. 1032
`
`

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`
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`241999
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`Exh. 1032
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`Oread, Palo Alto, CA
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`Product: Palonosetron HCI Intravenous
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`
`Formulation No.:
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`Client AD No.: N/A
`
`PID No.: 75941 MBR No.: DnB001.00
`Lot No.: 1 'l 3 'l 3 ~ 1.
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`Page2 of22
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`Exh. 1032