`
`Patent Application No. 10/616,709
`
`Applicant: Desai et al.
`
`Filed: July 10, 2003
`
`TC/AU: 1654
`
`Examiner: Roy R. Teller
`
`Docket No.: 223416
`
`Cu~tomer No.: 23460
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`Sir:
`
`REPLY TO OFFICE ACTION
`
`In reply to the Office Action dated March 13, 2007, please enter the following
`
`amendments and consider the following remarks.
`
`The claims pending in this application are reflected in the listing of claims which
`
`begins on page 2 of this paper.
`
`Remarks begin on page II of this paper.
`
`Page 1 of13
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`Dr. Reddy's Laboratories
`v.
`Fresenius Kabi USA, LLC
`U.S. Patent No. 8,476,010
`Exhibit 1017
`
`Exh. 1017
`
`
`
`Application No. 10/616,709
`
`Reply to Office Action
`
`AMENDMENTS TO THE CLAIMS
`
`This listing of claims replaces all prior versions, and listings, of claims in the application.
`
`1.
`
`(Currently Amended) A sterile pharmaceutical composition for pttreRteral
`
`adlfliAistration ofpropofol 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 ceffipesition is
`
`stored ia a eoataiRer kaviflg a elos~:~re wherein said closure is inert to propofol.
`
`2.
`
`(Original)
`
`The composition of claim I, wherein said composition further
`
`c omprises an aqueous phase and protein.
`
`3.
`
`(Original)
`
`T he sterile pharmaceutical composition of claim 2, wherein the
`
`protein is albumin.
`
`4.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 3, wherein the
`
`albumin is present in an amount of from about 0.01% to about 5% by weight of the
`
`composition.
`
`5.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 2, wherein the
`
`aqueous phase comprises water of injection and a pH modifier.
`
`6.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 2, wherein the
`
`composition comprises a tonicity agent.
`
`7.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 3, wherein the
`
`pH modifier is sodium hydroxide.
`
`8.
`
`(Orig inal)
`
`The sterile pharmaceutical composition of claim 6, wherein the
`
`tonicity agent is glycerin.
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`Page 2 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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`9.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 2, wherein
`
`s aid composition further comprises surfactant.
`
`10.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`said composition further comprises a solvent for propofol.
`
`11.
`
`(Original)
`
`The sterile pharmaceutical composition of claim lO whe rein the
`
`s olvent is a water-immiscible solvent.
`
`12.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 11, wherein
`
`the water-immiscible solvent is selected from the group consisting of soybean, safflower,
`
`cottonseed, 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
`
`mixtures thereof.
`
`13.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 12, wherein
`
`the water-immiscible solvent is soybean oil.
`
`14.
`
`(Original)
`
`The sterile pharmaceutical composition of claim lO, wherein
`
`the solvent is selected from the group consisting of chloroform, methylene chloride, ethy 1
`
`acetate, ethanol, tetrahydrofuran, dioxane, acetonitrile, acetone, dimethyl sulfoxide, dimethyl
`
`formamide, methyl pyrrolidinone, Cl-C20 alcohols, C2-C20 esters, C3-C20 ketones,
`
`polyethylene glycols, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated
`
`ihy drocarbons and combinations thereof.
`
`15.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 9, wherein the
`
`s urfactant is selected from the group consisting of phosphatides, synthetic phospholip£ds,
`
`natural phospholipids, lecithins, cthoxylatcd ethers and esters, tocopherol polyethylene glycol
`
`stearate, polypropylene-polyethylene block co-polymers, polyvinylpyrrolidone, and
`
`polyvinylalcohol and combinations thereof.
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`Page 3 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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`16.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 15, wherein
`
`the surfactant is selected from the group consisting of egg phosphatidcs, soya phosphrutidcs,
`
`egg lecithins, soya lecithins, and compositions thereof.
`
`17.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 16, wherein
`
`the surfactant is egg lecithin.
`
`18.
`
`(Original)
`
`The steri le pharmaceutical composition of claim I , wherein
`
`said closure is c.oated with a material inert to propofol.
`
`19.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`said closure is comprised of a material that is itself inert to propofol.
`
`20.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 19, wherein
`
`the material inert to propofol is selected from the group consisting of a fluoropolymer,
`
`silicone, and mixtures thereof.
`
`21.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 19, wherein
`
`said material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber,
`
`a f1uoropolymer, silicone, non-rubber, metal, and mixtures thereof:
`
`22.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 19, wherein
`
`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
`
`fluoropolymer, silicone, and miixtures thereof.
`
`23.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`said closure comprises bromobutyl rubber coated with a fluoropolymer.
`
`24.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`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.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`s aid closure comprises a non-rubber, or metal.
`
`26.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`said closure comprises chlorobutyl rubber coated with a fluoropolymer.
`
`27.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein
`
`s aid closure comprises siliconized chlorobutyl rubber.
`
`28.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 1, wherein the
`
`composition comprises propofol in an amount of from about 0.1% to about I 0% by weight of
`
`the composition, soybean oil in an amount of from about 0.5% to about 6% by weight of the
`
`c omposition, egg lecithin in an amount of from about 0.1% to about 5% by weight of the
`
`composition and human serum albumin in an amount of from about 0.1% to about 5% of the
`
`c omposition.
`
`29.
`in a container comprising in the form of an oil-in-water emulsion for parenteral
`
`(Currently Amended) A sterile pharmaceutical compos ition ofpropofol stored
`
`administration ofpropofol, said composition comprising an oil phase comprising
`
`propofol[[,]] and less than about 10% by weight solvent for propofol and an aqueous phase
`
`comprising water for injection., aREi wlierei-B the composition futiher comprising iRehides a
`
`stabilizing layer for the oil phase, said stabilizing layer comprising a surfactant and a protein,
`
`said container in which the composition is stored comprising a closure for the whereil'li said
`
`eOR'If'OSitios is stored iR a container~ h£¥viRg a elosure wherein said closure is inert to
`
`propofol.
`
`30.
`
`(Original)
`
`The composition of claim 29, wherein said protein is selected
`
`from the group consisting of albumins, globulins, immunoglobulins, lipoproteins, caseins,
`
`insulins, hemoglobins, lysozymcs, alpha-2-macroglobulin, fibroncctins, vitroncctins,
`
`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.
`
`(Original)
`
`The composition of claim 29, wherein the surfactant is selected
`
`from the group consisting of phosphatidcs, synthetic phospholipids natural phospholipids,
`
`lecithins, ethoxylated ethers and esters, tocopherol polyethylene glycol stearate,
`
`polypropylene-polyethylene block co-polymers, polyvinyl pyrrolidone, and polyvinylalcohol.
`
`32.
`
`(Original)
`
`The composition of claim 29, wherein said oil phase is propofol
`
`neat.
`
`33.
`
`(Original)
`
`The composition of claim 29, wherein said sUJfactant is lecithin
`
`and said protein is albumin.
`
`34.
`
`(Original)
`
`The composition of claim 29, wherein the oil phase includes a
`
`solvent, wherein said solvent is selected from the group consisting of soybean, safflower,
`
`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
`
`mixtures thereof, chloroform, methylene chloride, ethyl acetate, ethanol, tetrahydrofuran,
`
`dioxane, acetonitrile, acetone, dimethyl sulfoxide, dimethyl formamide, methyl
`
`pyrrolidinone, Cl-C20 alcohols, C2-C20 esters, C3-C20 ketones, polyethylene glycols,
`
`aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and combinations
`
`thereof.
`
`35.
`
`(Original)
`
`The composition of claim 34, wherein th e solvent is soybean
`
`oil.
`
`36.
`
`(Original)
`
`The composition of claim 35, wherein said soybean oil is
`
`present in an amount of from about 0. 5% to about 6% by weight of the composition.
`
`37.
`
`(Original)
`
`The composition of claim 33, wherein said egg lecithin is
`
`present in the composition in an amount of from about O. l % to about 5% by weight of the
`
`composition and said albumin is present in the composition in an amount of from about
`
`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.
`
`(Original)
`
`The composition of claim 37, wherein said oil phase includes
`
`soybean oil.
`
`39.
`
`(Original)
`
`The composition of claim 38, wherein said soybean oil is
`
`present in an amount of from about 0. 5% to about 6% by weight of the composition.
`
`40.
`
`(Original)
`
`The composition of c laim 38, wherein said soybean oil is
`
`present in said composition in an amount of from about 0.5% to about 3% by weight of the
`
`composition.
`
`41.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 31
`
`c omprising:
`
`a) about I% to 2% by weight of propofol,
`
`b) 3-6% by weight of soybean oil,
`
`c) 0.2- 1.0% by weight of egg lecithin,
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`d) about 2.25% by weight of glycerin,
`
`e) sodium hydroxide,
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`f) water to 100%, and
`
`g) pH between 5.0-8.5.
`
`42.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure is treated with a material inert to propofol.
`
`43.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure comprises a material that is itself inert to propofol.
`
`44.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 42, wherein
`
`the material inert to propofol is selected from the group consisting of a fluoropolymcr.
`
`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.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 43, wherein
`
`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
`
`fluoropolymer, silicone, non-rubber, metal, and mixtures thereof.
`
`46.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 46, wherein
`
`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
`
`fluoropolymer, silicone, and mixtures thereof.
`
`47.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure comprises bromobutyl rubber coated with a fluoropolymer.
`
`48.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure comprises siliconized bromobutyl rubber.
`
`49.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure comprises non-rubber, or metal.
`
`50.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure comprises chlorobutyl rubber coated with a fluoropolymer.
`
`51.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 29, wherein
`
`said closure comprises siliconized chlorobutyl rubber.
`
`52.
`
`(Currently Amended) A sterile, injectable pharmaceutical composition stored
`
`in a container comprising a closure. said composition comprising:
`
`a) microdroplets having a mean size of from about 20 nanometers to about 1000
`
`nanometers, said microdroplets comprising a sphere of propofol sunounded by a stabilizing
`
`layer comprising a phospholipid and devoid of oils capable of supporting bacterial growth;
`
`and
`
`b) a pharmaceutically acceptable injectable carrier,
`
`•wherein said container in which said composition is stored in a container having
`
`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)
`
`The composition of claim 52, wherein said composition further
`
`comprises albumin.
`
`54.
`
`(Original)
`
`The composition of claim 52, wherein said stabilizing layer
`
`includes albumin.
`
`55.
`
`(Original)
`
`The steri le pharmaceutical composition of claim 52, wherein
`
`said closure is c.oated with a material inert to propofol.
`
`56.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 52, wherein
`
`said closure comprises a material that is itself inert to propofol.
`
`57.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 55, wherein
`
`the material inert to propofol is selected from the group consisting of a fluoropolymer,
`
`silicone, and mixtures thereof.
`
`58.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 56, wherein
`
`the material is selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
`
`fluoropolymer, silicone, non-ntbber, metal, and mixtures thereof.
`
`59.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 55, wherein
`
`the material is selected from the group consisting of bromobutyl ntbber, chlorobutyl rubber, a
`
`fluoropolymer, silicone, and miixtures thereof.
`
`60.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 52, wherein
`
`said closure comprises bromobutyl rubber coated with a fluoropolymer.
`
`61.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 52, wherein
`
`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)
`
`The sterile pharmaceutical composition of claim 52, wherein
`
`said closure comprises a non-rubber, or metal.
`
`63.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 52, wherein
`
`said closure comprises chlorobutyl rubber coated with a fluoropolymer.
`
`64.
`
`(Original)
`
`The sterile pharmaceutical composition of claim 52, wherein
`
`said closure comprises siliconized chlorobutyl rubber.
`
`A container comprising a propofol composition therein,
`65.
`wherein the container comprises a closure that is inert to propofol, and wherein the propofol
`
`(New)
`
`composition comprises propofol and less than about 10% by weight solvent for propofol.
`
`The container of claim 65, wherein the closure comprises a
`66.
`material selected from the group consisting of bromobutyl rubber, chlorobutyl rubber, a
`
`(New)
`
`fluoropolymer, silicone, non-rubber, metal and mixtures thereof.
`
`67.
`
`(New)
`
`The container of claim 66, wherein the material comprises a
`
`fluoropolymer.
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`Page 10 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
`
`Reconsideration of the pending application is respectfully requested in view of the
`
`REMARKS
`
`following remarks.
`
`Status of the Application
`
`Claims 1-67 are pending. Of these, claims 1, 29 and 52 have been amended, and
`
`claims 65-67 are new. As the amended claims are fully supported by the application as filed,
`
`no new matter has been added to the application by way of these amendments.
`
`Summar)' of the Office Action
`
`Claims 1-17, 28-41, and 52-54 are provisionally rejected under the judicially-created
`
`doctrine of obviousness-type double patenting over claims 1-47 of copending U.S. Patent
`
`Application No. 10/434,776.
`
`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
`
`anticipation rejection.
`
`Zhang et al. discloses and teaches compositions containing propofol- without more.
`
`Indeed, the sole focus of Zhang ct al. is directed to obtaining a propofol formulation that is
`
`bacteriostatic or fungistatic. Zhang et al. purportedly teaches that the solution to microbial
`
`growth is to limit the content of lecithin and soybean oil in propofol formulations.
`
`In marked contmst, the pending claims provide, in one aspect, a sterile pharmaceutical
`
`composition ofpropofol 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
`
`claim 1.
`
`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,
`
`let alone provide any recognition or suggestion that a container, or the components used in
`
`the container, may somehow be relevant to its propofol compositions. Because of this
`
`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.
`
`Page 12 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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`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
`
`Page 13 of 13
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`Exh. 1017
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