IN THE UNITED STATES PA TENT AND TRADEMARK OFFICE
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`
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`Patent Application No. 10/616,709
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`Applicant: Desai ct al.
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`July 10, 2003
`Filed:
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`TC/AU: 1654
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`
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`Examiner: Roy R. Teller
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`Docket No.: 223416
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`Customer
`No.: 23460
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`Commissioner for Patents
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`P.O. Box 1450
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`Alexandria, VA 22313-1450
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`Sir:
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`REPLY TO OFFICE ACTION
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`
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`In reply to the Office Action dated March 13, 2007, please enter the following
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`amendments and consider the following remarks.
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`The claims pending in this appUcation are reflected in the listing of claims which
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`begins on page 2 of this paper.
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`Remarks begin on page 11 of this paper.
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`Page I of 13
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`Bass and Spangenberg
`v.
`Fresenius Kabi USA, LLC
`nt No. 8,476,010
`U.S. Pate
`Exhibit 1017
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`Exh. 1017
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`

`
`Application No. 10/616,709
`
`Reply to Office Action
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`AMENDMENTS TO THE CLAIMS
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`This listing of claims replaces all prior versions, and listings, of claims in the application.
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`1.
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`(Currently Amended) A sterile pharmaceutical composition for pttreRteral
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`adlfliAistration ofpropofol stored in a container, said composition comprising propofol[[,]]
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`and less than about 10% by weight solvent for propofol, said container in which said
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`composition is stored comprising a closure for said container. wherein said ceffipesition is
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`stored ia a eoataiRer kaviflg a elos~:~re wherein said closure is inert to propofol.
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`2.
`
`(Original)
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`The composition of claim I, wherein said composition further
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`c omprises an aqueous phase and protein.
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`3.
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`(Original)
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`T he sterile pharmaceutical composition of claim 2, wherein the
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`protein is albumin.
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`4.
`
`(Original)
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`The sterile pharmaceutical composition of claim 3, wherein the
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`albumin is present in an amount of from about 0.01% to about 5% by weight of the
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`composition.
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`5.
`
`(Original)
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`The sterile pharmaceutical composition of claim 2, wherein the
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`aqueous phase comprises water of injection and a pH modifier.
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`6.
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`(Original)
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`The sterile pharmaceutical composition of claim 2, wherein the
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`composition comprises a tonicity agent.
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`7.
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`(Original)
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`The sterile pharmaceutical composition of claim 3, wherein the
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`pH modifier is sodium hydroxide.
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`8.
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`(Orig inal)
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`The sterile pharmaceutical composition of claim 6, wherein the
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`tonicity agent is glycerin.
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`Page 2 of 13
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`Exh. 1017
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`

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`Application No. 10/616,709
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`Reply to Office Action
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`9.
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`(Original)
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`The sterile pharmaceutical composition of claim 2, wherein
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`s aid composition further comprises surfactant.
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`10.
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`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`said composition further comprises a solvent for propofol.
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`11.
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`(Original)
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`The sterile pharmaceutical composition of claim lO whe rein the
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`s olvent is a water-immiscible solvent.
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`12.
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`(Original)
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`The sterile pharmaceutical composition of claim 11, wherein
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`the water-immiscible solvent is selected from the group consisting of soybean, safflower,
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`cottonseed, corn, coconut, sunflower, arachis, castor sesame, orange, limonene or olive oil, an
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`ester of a medium or long-chain fatty acid, a chemically modified or manufactured palmitate,
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`glyceral ester or polyoxyl, hydrogenated castor oil, a marine oil, fractionated oils, and
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`mixtures thereof.
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`13.
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`(Original)
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`The sterile pharmaceutical composition of claim 12, wherein
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`the water-immiscible solvent is soybean oil.
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`14.
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`(Original)
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`The sterile pharmaceutical composition of claim lO, wherein
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`the solvent is selected from the group consisting of chloroform, methylene chloride, ethy 1
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`acetate, ethanol, tetrahydrofuran, dioxane, acetonitrile, acetone, dimethyl sulfoxide, dimethyl
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`formamide, methyl pyrrolidinone, Cl-C20 alcohols, C2-C20 esters, C3-C20 ketones,
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`polyethylene glycols, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated
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`ihy drocarbons and combinations thereof.
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`15.
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`(Original)
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`The sterile pharmaceutical composition of claim 9, wherein the
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`s urfactant is selected from the group consisting of phosphatides, synthetic phospholip£ds,
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`natural phospholipids, lecithins, cthoxylatcd ethers and esters, tocopherol polyethylene glycol
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`stearate, polypropylene-polyethylene block co-polymers, polyvinylpyrrolidone, and
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`polyvinylalcohol and combinations thereof.
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`Page 3 of 13
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`Exh. 1017
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`

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`Application No. 10/616,709
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`Reply to Office Action
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`16.
`
`(Original)
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`The sterile pharmaceutical composition of claim 15, wherein
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`the surfactant is selected from the group consisting of egg phosphatidcs, soya phosphrutidcs,
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`egg lecithins, soya lecithins, and compositions thereof.
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`17.
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`(Original)
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`The sterile pharmaceutical composition of claim 16, wherein
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`the surfactant is egg lecithin.
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`18.
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`(Original)
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`The steri le pharmaceutical composition of claim I , wherein
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`said closure is c.oated with a material inert to propofol.
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`19.
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`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`said closure is comprised of a material that is itself inert to propofol.
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`20.
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`(Original)
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`The sterile pharmaceutical composition of claim 19, wherein
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`the material inert to propofol is selected from the group consisting of a fluoropolymer,
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`silicone, and mixtures thereof.
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`21.
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`(Original)
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`The sterile pharmaceutical composition of claim 19, wherein
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`said material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber,
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`a f1uoropolymer, silicone, non-rubber, metal, and mixtures thereof:
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`22.
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`(Original)
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`The sterile pharmaceutical composition of claim 19, wherein
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`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
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`fluoropolymer, silicone, and miixtures thereof.
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`23.
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`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`said closure comprises bromobutyl rubber coated with a fluoropolymer.
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`24.
`
`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`said closure comprises siliconized bromobutyl rubber.
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`Page 4 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`25.
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`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`s aid closure comprises a non-rubber, or metal.
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`26.
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`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`said closure comprises chlorobutyl rubber coated with a fluoropolymer.
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`27.
`
`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein
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`s aid closure comprises siliconized chlorobutyl rubber.
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`28.
`
`(Original)
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`The sterile pharmaceutical composition of claim 1, wherein the
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`composition comprises propofol in an amount of from about 0.1% to about I 0% by weight of
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`the composition, soybean oil in an amount of from about 0.5% to about 6% by weight of the
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`c omposition, egg lecithin in an amount of from about 0.1% to about 5% by weight of the
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`composition and human serum albumin in an amount of from about 0.1% to about 5% of the
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`c omposition.
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`29.
`in a container comprising in the form of an oil-in-water emulsion for parenteral
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`(Currently Amended) A sterile pharmaceutical compos ition ofpropofol stored
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`administration ofpropofol, said composition comprising an oil phase comprising
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`propofol[[,]] and less than about 10% by weight solvent for propofol and an aqueous phase
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`comprising water for injection., aREi wlierei-B the composition futiher comprising iRehides a
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`stabilizing layer for the oil phase, said stabilizing layer comprising a surfactant and a protein,
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`said container in which the composition is stored comprising a closure for the whereil'li said
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`eOR'If'OSitios is stored iR a container~ h£¥viRg a elosure wherein said closure is inert to
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`propofol.
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`30.
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`(Original)
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`The composition of claim 29, wherein said protein is selected
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`from the group consisting of albumins, globulins, immunoglobulins, lipoproteins, caseins,
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`insulins, hemoglobins, lysozymcs, alpha-2-macroglobulin, fibroncctins, vitroncctins,
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`fibrinogens, lipases, peptides, enzymes, antibodies and combinations thereof.
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`Page 5 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`31.
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`(Original)
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`The composition of claim 29, wherein the surfactant is selected
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`from the group consisting of phosphatidcs, synthetic phospholipids natural phospholipids,
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`lecithins, ethoxylated ethers and esters, tocopherol polyethylene glycol stearate,
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`polypropylene-polyethylene block co-polymers, polyvinyl pyrrolidone, and polyvinylalcohol.
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`32.
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`(Original)
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`The composition of claim 29, wherein said oil phase is propofol
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`neat.
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`33.
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`(Original)
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`The composition of claim 29, wherein said sUJfactant is lecithin
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`and said protein is albumin.
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`34.
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`(Original)
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`The composition of claim 29, wherein the oil phase includes a
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`solvent, wherein said solvent is selected from the group consisting of soybean, safflower,
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`c ottonseed, corn, coconut, sunflower, arachis, castor sesame, orange, limonene or olive oil, an
`
`ester of a medium or long-chain fatty acid, a chemically modified or manufactured palmitate,
`
`glyceral ester or polyoxyl, hydrogenated castor oil, a marine oil, fractionated oils, and
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`mixtures thereof, chloroform, methylene chloride, ethyl acetate, ethanol, tetrahydrofuran,
`
`dioxane, acetonitrile, acetone, dimethyl sulfoxide, dimethyl formamide, methyl
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`pyrrolidinone, Cl-C20 alcohols, C2-C20 esters, C3-C20 ketones, polyethylene glycols,
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`aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and combinations
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`thereof.
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`35.
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`(Original)
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`The composition of claim 34, wherein th e solvent is soybean
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`oil.
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`36.
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`(Original)
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`The composition of claim 35, wherein said soybean oil is
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`present in an amount of from about 0. 5% to about 6% by weight of the composition.
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`37.
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`(Original)
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`The composition of claim 33, wherein said egg lecithin is
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`present in the composition in an amount of from about O. l % to about 5% by weight of the
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`composition and said albumin is present in the composition in an amount of from about
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`0.01% to about 5% by weight of the composition.
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`Page 6 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`38.
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`(Original)
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`The composition of claim 37, wherein said oil phase includes
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`soybean oil.
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`39.
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`(Original)
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`The composition of claim 38, wherein said soybean oil is
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`present in an amount of from about 0. 5% to about 6% by weight of the composition.
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`40.
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`(Original)
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`The composition of c laim 38, wherein said soybean oil is
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`present in said composition in an amount of from about 0.5% to about 3% by weight of the
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`composition.
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`41.
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`(Original)
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`The sterile pharmaceutical composition of claim 31
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`c omprising:
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`a) about I% to 2% by weight of propofol,
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`b) 3-6% by weight of soybean oil,
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`c) 0.2- 1.0% by weight of egg lecithin,
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`d) about 2.25% by weight of glycerin,
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`e) sodium hydroxide,
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`f) water to 100%, and
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`g) pH between 5.0-8.5.
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`42.
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`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure is treated with a material inert to propofol.
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`43.
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`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure comprises a material that is itself inert to propofol.
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`44.
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`(Original)
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`The sterile pharmaceutical composition of claim 42, wherein
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`the material inert to propofol is selected from the group consisting of a fluoropolymcr.
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`silicone, and mixtures thereof.
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`Page 7 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`45.
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`(Original)
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`The sterile pharmaceutical composition of claim 43, wherein
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`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
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`fluoropolymer, silicone, non-rubber, metal, and mixtures thereof.
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`46.
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`(Original)
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`The sterile pharmaceutical composition of claim 46, wherein
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`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
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`fluoropolymer, silicone, and mixtures thereof.
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`47.
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`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure comprises bromobutyl rubber coated with a fluoropolymer.
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`48.
`
`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure comprises siliconized bromobutyl rubber.
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`49.
`
`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure comprises non-rubber, or metal.
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`50.
`
`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure comprises chlorobutyl rubber coated with a fluoropolymer.
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`51.
`
`(Original)
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`The sterile pharmaceutical composition of claim 29, wherein
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`said closure comprises siliconized chlorobutyl rubber.
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`52.
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`(Currently Amended) A sterile, injectable pharmaceutical composition stored
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`in a container comprising a closure. said composition comprising:
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`a) microdroplets having a mean size of from about 20 nanometers to about 1000
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`nanometers, said microdroplets comprising a sphere of propofol sunounded by a stabilizing
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`layer comprising a phospholipid and devoid of oils capable of supporting bacterial growth;
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`and
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`b) a pharmaceutically acceptable injectable carrier,
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`•wherein said container in which said composition is stored in a container having
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`comprising a closure for said container, wherein said closure is inert to propofol.
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`Page 8 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`53.
`
`(Original)
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`The composition of claim 52, wherein said composition further
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`comprises albumin.
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`54.
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`(Original)
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`The composition of claim 52, wherein said stabilizing layer
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`includes albumin.
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`55.
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`(Original)
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`The steri le pharmaceutical composition of claim 52, wherein
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`said closure is c.oated with a material inert to propofol.
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`56.
`
`(Original)
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`The sterile pharmaceutical composition of claim 52, wherein
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`said closure comprises a material that is itself inert to propofol.
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`57.
`
`(Original)
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`The sterile pharmaceutical composition of claim 55, wherein
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`the material inert to propofol is selected from the group consisting of a fluoropolymer,
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`silicone, and mixtures thereof.
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`58.
`
`(Original)
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`The sterile pharmaceutical composition of claim 56, wherein
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`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
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`fluoropolymer, silicone, non-ntbber, metal, and mixtures thereof.
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`59.
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`(Original)
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`The sterile pharmaceutical composition of claim 55, wherein
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`the material is selected from the group consisting of bromobutyl ntbber, chlorobutyl rubber, a
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`fluoropolymer, silicone, and miixtures thereof.
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`60.
`
`(Original)
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`The sterile pharmaceutical composition of claim 52, wherein
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`said closure comprises bromobutyl rubber coated with a fluoropolymer.
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`61.
`
`(Original)
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`The sterile pharmaceutical composition of claim 52, wherein
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`said closure comprises siliconized bromobutyl ntbber.
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`Page 9 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`62.
`
`(Original)
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`The sterile pharmaceutical composition of claim 52, wherein
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`said closure comprises a non-rubber, or metal.
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`63.
`
`(Original)
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`The sterile pharmaceutical composition of claim 52, wherein
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`said closure comprises chlorobutyl rubber coated with a fluoropolymer.
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`64.
`
`(Original)
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`The sterile pharmaceutical composition of claim 52, wherein
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`said closure comprises siliconized chlorobutyl rubber.
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`A container comprising a propofol composition therein,
`65.
`wherein the container comprises a closure that is inert to propofol, and wherein the propofol
`
`(New)
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`composition comprises propofol and less than about 10% by weight solvent for propofol.
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`The container of claim 65, wherein the closure comprises a
`66.
`material selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
`
`(New)
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`fluoropolymer, silicone, non-rubber, metal and mixtures thereof.
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`67.
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`(New)
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`The container of claim 66, wherein the material comprises a
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`fluoropolymer.
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`Page 10 of 13
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`Exh. 1017
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`

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`Application No. 10/616,709
`
`Reply to Office Action
`
`Reconsideration of the pending application is respectfully requested in view of the
`
`REMARKS
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`following remarks.
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`Status of the Application
`
`Claims 1-67 are pending. Of these, claims 1, 29 and 52 have been amended, and
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`claims 65-67 are new. As the amended claims are fully supported by the application as filed,
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`no new matter has been added to the application by way of these amendments.
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`Summar)' of the Office Action
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`Claims 1-17, 28-41, and 52-54 are provisionally rejected under the judicially-created
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`doctrine of obviousness-type double patenting over claims 1-47 of copending U.S. Patent
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`Application No. 10/434,776.
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`Claims 1 and 5-64 are further rejected under 35 U.S.C. § 102(b) as allegedly
`
`unpatentable over U.S. Patent 6,399,087 ("Zhang ct al. ").
`
`Discussion
`
`Turning initially to the substantive rejection, Applicants respectfully traverse the
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`anticipation rejection.
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`Zhang et al. discloses and teaches compositions containing propofol- without more.
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`Indeed, the sole focus of Zhang ct al. is directed to obtaining a propofol formulation that is
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`bacteriostatic or fungistatic. Zhang et al. purportedly teaches that the solution to microbial
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`growth is to limit the content of lecithin and soybean oil in propofol formulations.
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`In marked contmst, the pending claims provide, in one aspect, a sterile pharmaceutical
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`composition ofpropofol stored in a container, said composition comprising propofol and less
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`than about 10% by weight solvent for propofol, said container in which said composition is
`
`stored comprising a closure for said container, wherein said closure is inert to propofol. See
`
`claim 1.
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`Page 11 of 13
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`Exh. 1017
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`Application No. 10/616,709
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`Reply to Office Action
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`In contrast to the pending claims, Zhang et al. does not disclose any container at all,
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`let alone provide any recognition or suggestion that a container, or the components used in
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`the container, may somehow be relevant to its propofol compositions. Because of this
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`deficiency, Zhang et al. would not motivate one skilled in the art to provide the subject matter
`
`described by the pending claims, e.g., a sterile pharmaceutical composition of propofol stored
`
`in a container, said composition comprising propofol and less than about 10% by weight
`
`solvent for propofol, said container in which said composition is stored comprising a closure
`
`for said container, wherein said closure is inert to propofol. See, e.g., claim I.
`
`Further in this regard, Z11ang et al. fails to recognize that degradation or potency loss
`
`of a propofol composition may occur despite providing a propofol formulation having a
`
`relatively low amount of solvent. Thus, Zhang ct al. fails to motivate one skilled in the art to
`
`provide the invention as claimed which includes, inter alia, a sterile pharmaceutical
`
`composition of propofol stored in a container, said composition comprising propofol and less
`
`than about I 0% by weight solvent for propofol, said container in which said composition is
`
`stored comprising a closure for said container, wherein said closure is inert to propofol. See,
`
`e.g., claim 1.
`
`In view ofthe foregoing, Applicants respectfully submit that Zlhang et al. fails to
`
`anticipate the claimed inventions, and further fails to render the inventions obvious.
`
`Withdrawal of the anticipation rejection is thus respectfully requested.
`
`In regard to the obviousness-type double patenting rejection, Applicants may file a
`
`terminal disclaimer addressing this rejection upon receipt of an indication of allowable
`
`subject matter.
`
`Conclusion
`
`Applicants respectfully submit that the patent application is in condition for
`allowance. If, in the opinion of the Examiner, a telephone conference would expedite the
`
`prosecution of the subject application, the Examiner is invited to call the undersigned
`
`attorney.
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`Page 12 of 13
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`Exh. 1017
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`Application No. 10/616,709
`
`Reply to Office Action
`
`Respectfully submitted,
`
`/Christopher T. Griffith/
`Registration No. 33,392
`LEYDIG, VOlT & tvlAYER, LTD.
`Two Prudential Plaza, Suite 4900
`180 North Stetson Avenue
`Chicago, Illinois 60601 -673 1
`(312) 616-5600 (telephone)
`(3 12) 616-5700 (facsimi le)
`
`Date: September 6, 2007
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`Page 13 of 13
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`Exh. 1017