IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
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`In re Application of: Duncan et al.
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`Examiner: L. Beckhardt
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`Application No.: 12/971,084
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`TC/Art Unit: 1613
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`Filed: December 17, 2010
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`Title: METHODS OF TREATMENT WITH
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`PRE-MIXED, READY-TO—USE
`PHARMACEUTICAL COMPOSITIONS
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`Attorney Docket Number: 19015-221
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`Mail Stop Amendment
`Commissioner for Patents
`PO. Box 1450
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`Alexandria, VA 22313—1450
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`AMENDMENT AND INTERVIEW SUMMARY
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`Sir:
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`This communication is being filed in response to the November 30, 2012 Office Action
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`issued in connection with the above-referenced application. A response to the Office Action is
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`due February 28, 2013. Accordingly, this response is timely filed.
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`Amendments to the Claims are reflected in the Listing of Claims which begins on page
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`2 of this paper.
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`Remarks begin on page 7 of this paper.
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`Sandoz
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`Exhibit1017
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`us. App. No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`I.
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`Amendments to the Claims
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`This listing of claims shall replace all prior versions, and listings, of claims in the
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`application.
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`Listing of Claims
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`1—39. Canceled.
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`40. (Currently Amended) A method for treating acute elevations of blood pressure in a human
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`subject in need thereof, said method comprising parenterally administering a eempesitien
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`eenepflsmg pre—mixed aqueous solution comprising from about 0.1 to 0.4 mg/mL nicardipine or
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`a pharmaceutically acceptable salt thereof; a tonicity agent; and a buffer; wherein the
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`eempositiefl agueous solution requires no dilution before administration and has a pH from about
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`3.6 to about 4.7, the eempesitien agueous solution stored in a container such that the aqueous
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`solution is in contact with non-pplar polymers. the aqueous solution when stored in the container
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`for at least three months at room temperature exhibiting (i) less than a 10% decrease in the
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`concentration of nicardipine or pharmaceuticallv acceptable salt thereof and (ii) a total impurity
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`formation of less than about 3%.
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`41. (Currently Amended) A method for inducing hypotension in a human subject in need
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`thereof, said method comprising parenterally administering a composition—comprising pre—mixed
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`aqueous solution comprising from about 0.1 to 0.4 mg/mL nicardipine or a pharmaceutically
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`acceptable salt thereof; a tonicity agent; and a buffer; wherein the eempesitien aqueous solution
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`requires no dilution before administration and has a pH from about 3.6 to about 4.7, the
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`eompositiea agueous solution stored in a container such that the aqueous solution is in contact
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`with no_n_-p_o_lar polymers_,_the_a_queous solution when stored in the container for at least three
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`months at room temperature exhibiting (i) less than a 10% decrease in the concentration of
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`nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity formation of less
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`than about 3%.
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`42. (Currently Amended) A method for treating acute elevations of blood pressure in a human
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`subject in need thereof, said method comprising parenterally administering to a subject in need
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`-2-
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`Sandoz
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`U.S. App, No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`thereof, a pre-mixed aqueous solution with a pH from about 3.6 to about 4.7 comprising: from
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`about 0.1 to 0.4 mg/mL nicardipine hydrochloride; a tonicity agent selected from (i) about 4.5%
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`to about 5% dextrose or (ii) about 0.8% to about 0.9% sodium chloride; and lbuffer flora—about
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`W; the aqueous solution contained in a pharmaceutically
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`acceptable container such that the aqueous solution is in contact with non-polar polymers the
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`aqueous solution when stored in the container for at least three months at room temperature
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`exhibiting (i) less than a 10% decrease in the concentration ofnicardipine or pharmaceutically
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`acceptable salt thereof and (ii) a total impurity formation of less than about 3%.
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`43. (Previously Presented) The method of claim 42, further comprising at least one pH adjuster
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`selected from the group consisting of hydrochloric acid, sodium hydroxide and a mixture thereof.
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`44. ((Previously Presented) The method ofclaim 42, further comprising from about 1 mg/rnl to
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`about 4 mg/ml sorbitol.
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`45. (Currently Amended) The method of claim 42, wherein the nonflar polymers comprise
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`eentaineeeemprises copolyester, polyethylene or polyolefin.
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`46. (Currently Amended) The method of claim 42, wherein the pre-mixed aqueous solution
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`comprises: from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride; gig a tonicity agent
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`selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL
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`sodium chloridefifid-EWWWW.
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`47. (Currently Amended) A method for inducing hypotension in a human subject in need thereof
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`said method comprising parenterally administering to a subject in need thereof, a pre-mixed
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`aqueous solution with a pH from about 3.6 to about 4.7 comprising: from about 0.1 to 0.4
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`mg/mL nicardipine hydrochloride; a tonicity agent selected from (i) about 4.5% to about 5%
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`dextrose or (ii) about 0.8% to about 0.9% sodium chloride; and a buffer fiemabothTQJ—teabeut
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`Grl—mgyimL—ei-trie—aeid; the aqueous solution contained in a pharmaceutically acceptable container
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`such that the solutionW is in contact with non-
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`polar polymers, the aqueous solution when stored in the container for at least three months at
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`-3-
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`US. App. No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`room temperature exhibiting (i) less than a 10% decrease in the concentration of nicardipine or
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`pharmaceuticallv acceptable salt thereof and (ii) a total impurity formation of less than about 3%.
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`48. (Previously Presented) The method of claim 47, further comprising at least one pH adjuster
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`selected from the group consisting of hydrochloric acid, sodium hydroxide and a mixture thereof.
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`49. (Previously Presented) The method of claim 47, further comprising from about 1 mg/ml to
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`about 4 mg/ml sorbitol.
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`50. (Currently Amended) The method of claim 47, wherein the non—polar polymers comprise
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`69W copolycster, polyethylene or polyolefin.
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`51. (Currently Amended) The method of claim 47, wherein the pre-mixed aqueous solution
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`comprises: from about 0.1 to about 0.2 mg/mL nicardipine hydrochloride; and a tonicity agent
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`selected from (i) about 46 to about 50 mg/mL dextrose or (ii) about 8.3 to about 9 mg/mL
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`sodium cltloridewmmm about 0.49384 mgmil citric acid.
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`52. (New) The method of claim 40, wherein the wherein the non-polar polymers comprise
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`copolyester, polyethylene or polyolefin.
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`53. (New) The method of claim 41, wherein the wherein the non-polar polymers comprise
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`copolyester, polyethylene or polyolefin.
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`54, (New) The method of claim 40, wherein the non-polar polymers comprise polyethylene.
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`55. (New) The method of claim 41, wherein the non-polar polymers comprise polyethylene.
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`56. (New) The method of claim 42, wherein the non~polar polymers comprise polyethylene.
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`57. (New) The method ofclaim 47, wherein the non-polar polymers comprise polyethylene.
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`Sandoz
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`U.S. App.No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`58. (New) The method of claim 40, wherein the aqueous solution when stored in the container
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`for at
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`least one ycar at room temperature exhibits (i)
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`less than a 10% decrease in the
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`concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity
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`formation of less than about 3%.
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`59. (New) The method of claim 41, wherein the aqueous solution when stored in the container
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`for at
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`least one year at room temperature exhibits (i)
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`less than a 10% decrease in the
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`concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity
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`formation of less than about 3%.
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`60. (New) The method of claim 42, wherein the aqueous solution when stored in the container
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`for at
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`least one year at room temperature exhibits (i)
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`less than a 10% decrease in the
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`concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity
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`formation of less than about 3%.
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`61. (New) The method of claim 47, wherein the aqueous solution when stored in the container
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`for at
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`least one year at room temperature exhibits (i)
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`less than a 10% decrease in the
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`concentration of nicardipine or pharmaceutically acceptable salt thereof and (ii) a total impurity
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`formation of less than about 3%.
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`62. (New) The method of claim 40, further comprising from about 0 mg/mL to about 4 mg/mL
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`sorbitol.
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`63. (New) The method of claim 41, further comprising from about 0 mg/mL to about 4 mg/mL
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`sorbitol.
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`64. (New) The method of claim 42, further comprising from about 0 mg/mL to about 4 mg/mL
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`sorbitol.
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`65. (New) The method of claim 47, further comprising from about 0 mg/mL to about 4 mg/mL
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`sorbitol.
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`Sandoz
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`U.S. App. No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`66. (New) The method of claim 40. wherein the pre—mixed aqueous solution comprises from
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`about 0.1 to about 0.2 mg/mL nicardipine hydrochloride.
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`67. (New) The method of claim 41, wherein the pre-mixed aqueous solution comprises from
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`about 0.1 to about 0.2 mg/mL nicardipinc hydrochloride.
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`68. (New) The method of claim 42, wherein the pre-mixed aqueous solution comprises from
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`about 0.1 to about 0.2 mg/mL nicardipine hydrochloride.
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`69. (New) The method of claim 47. wherein the pre-mixed aqueous solution comprises from
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`about 0.1 to about 0.2 mg/mL nicardipine hydrochloride.
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`Sandoz
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`U.S. App. No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`II.
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`Remarks
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`A.
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`Status of the Claims
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`Claims 40-69 will be pending after entry of this amendment. Claims 1-39 have been
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`previously canceled without prejudice. Claims 40, 41, 42, 45, 46, 47, 50 and 51 have been
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`amended without prejudice. New claims 52-69 have been added.
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`Support for the amendments to the claims are found throughout the specification as
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`originally filed, e.g., the original claims and paragraphs 21, 33, 35, 48 and 87.
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`Applicants respectfully submit that no new matter has been added by Virtue of the present
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`amendments.
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`B. Summary of Interview
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`Applicants wish to thank Examiner Beckhardt and Examiner Long for the courtesies
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`extended in the January 29, 2013 Interview with Applicants’ representative? Robert J. Paradiso.
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`During the interview, US Patent No. 5,164,405 (McFarlane): Baaske and Zeidler were discussed
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`as set forth in Section C. below. Also discussed was the Declaration of Dr. Brittain (submitted
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`herewith) from the parent application.
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`Applicants discussed that the limitations regarding the composition in a container such
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`that the solution is in contact with non-polar polymers or the specific polymers recited in the
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`claims address the anticipatory rejections of the office action. Applicants also discussed the
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`unexpected stability obtained by the present
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`invention, e.g., when the composition is in a
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`container such that the solution is in contact with non-polar polymers or the specific polymers
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`recited in the claims. The Examiner was directed to Figures 5A and 5B of the application and
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`the accompanying discussion in the Declaration of Dr. Brittain to support this position.
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`use App. No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`C.
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`Claim Rejections Under 35 U.S.C. § 102 and 35 U.S.C. § 103
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`1. The Baaske reference
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`In the Office Action, claims 40, 42-44 and 46 were rejected 35 U.S.C. § 102(b) as being
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`anticipated by Baaske as evidenced by PDL Biopharma and VislV.
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`As discussed during the Interview, the Baaske reference (with or without reference to
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`PDL Biopharma and VislV) does not teach or suggest the limitation that the aqueous solution is
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`in contact with non-polar polymers as recited in claims 40-42 and 47 (or the specific polymers
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`recited in claims 45, 50 and 52-57)
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`Accordingly, Applicants respectfully request that the rejection under 35 U.S.C. § 102
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`over the Baaske reference be removed.
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`2. The Baaske reference in view of the Hersey, Varon and Zeidler references
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`In the Office Action, claims 40-51 were rejected under 35 U.S.C. § 103(a) as being
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`unpatentable over the Baaske reference in view of the Hersey, Varon and Zeidler references.
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`As discussed during the interview, the Zeidler reference does not provide any teachings
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`regarding nicardipine nor the long term stability that can be provide to an aqueous nicardipine
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`formulation wherein the aqueous solution is in contact with non-polar polymers as recited in
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`claims 40—42 and 47 (or the specific polymers recited in claims 45, 50 and 52-57). This is based
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`on the very least, that Zeidler does not discuss nicardipine and also does not provide any
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`discussion of stability beyond 24 hours. Therefore, the Zeidler reference does not cure the
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`deficiencies of the Baaske reference as stated above. Even if the Zeidler reference mentioned
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`nicardipine (which it does not), any teachings therein would be inconclusive as there is no
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`discussion of stability beyond 24 hours. The Hersey reference is cited for teaching nicardipine
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`for the treatment of hypotension and the Varon reference is cited for teaching nicardipine for the
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`treatment of acute elevations ofblood pressure. These references also do not cure the
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`deficiencies of Baaske as stated above.
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`US. App. No. 12/971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`Accordingly, Applicants respectfully request that the rejection under 35 U.S.C. § 103(a)
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`over the Baaske reference in View of the Hersey, Varon and Zeidler references be removed.
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`3. The Brittain Declaration
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`In further support of the patentability of the present invention over any of the Baaske,
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`McFarlane, Hersey, Varon or Zeidler references alone or in any combination, the Examiner is
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`directed to the Declaration of Dr. Harry Brittain that among other positions of patentability,
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`includes a discussion on the unexpected stability obtained by the presently claimed limitations on
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`the container. The Examiner is directed to page 4, paragraph 2 of the Brittain Declaration which
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`states as follows:
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`“... As shown in Figure 5A, the “0/0 Drug Remaining” after 12 weeks of storage in
`a polyvinyl chloride (PVC) container (lntravia®) resulted in a nicardipine
`hydrochloride net decrease of over 15%. PVC is the material described in the
`McFarlane reference for storage of the reconstituted nicardipine hydrochloride
`concentrate. In contrast, as shown in Figure SB of US Patent Application Serial
`No. 2007/0249689, when low concentration nicardipine hydrochloride is stored in
`a non—polar bag (e.g., Galaxy®) there is surprisingly minimal degradation even
`after 25 weeks storage.
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`Accordingly, Applicants respectfitlly request that the rejections under 35 U.S,C. § 103(a)
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`over the cited references be removed.
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`D. Double Patenting Rejections
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`In the Office Action, claims 40-51 were rejected on the ground of nonstatutory
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`obviousness-type double patenting as being unpatentable over claims 1-12 of US. Patent No.
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`7,659,291. In response, Applicants hereby file a terminal disclaimer over US. Patent No.
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`7,659,291. Accordingly, Applicants respectfully request the double patenting rejection be
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`removed.
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`Sandoz
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`U.S. App. No. 12 “971,084
`Response to Office Action dated November 30, 2012
`Amendment dated February 28, 2013
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`Applicants note that the filing of a Terminal Disclaimer is not an admission, acquiescence
`
`or estoppel on the merits of an issue of obviousness. See Quad Environment Technologies Corp.
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`v. Union Sanitary District, 946 F.2d 870, 873‘74, 20 U.S.P.Q. 2d 1392, 1394—95 (Fed. Cir.
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`1991).
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`III.
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`Conclusion
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`It is believed that all claims are in condition for allowance. If the Examiner believes that
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`issues may be resolved by a telephone interview,
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`the Examiner is invited to telephone the
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`undersigned at
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`(973) 597—2404.
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`The undersigned may also be contacted by e—mail at
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`rparadiso@lowenstein.com. All correspondence should be directed to the address listed below.
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`AUTHORIZATION
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`The Commissioner is hereby authorized to charge any fees that may be required, or credit
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`any overpayment, to Deposit Account 50-1358.
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`Respectfully submitted,
`Lowenstein Sandler LLP
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`/Robert J. Paradise /
`
`By: Robert J. Paradiso
`Attorney for Applicant
`Registration No. 41,240
`
`DOCKET ADMINISTRATOR
`LOWENSTEIN SANDLER PC
`
`65 Livingston Avenue
`Roseland, NJ 07068
`General Tel.: 973-597—2500
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