UNITED ST A TES p A TENT AND TRADEMARK OFFICE
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`u:,.JTED STA TES DEPARTMENT OF COM.."\IIERCE
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`UnHcd Stales Patent and Trademark Office
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`Address: COM'll!ISS!ONER FOR PATh'iTS
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`P.O. Bo, 1450
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`Alex.::».ndri.i., Virg.ini:l 2231J..1450
`www.uspto,gov
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`APPLICATION NO.
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`FILING DATE
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`FIRSTNA..l\1EDINVENTOR
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`AITOR.t'IEY DOCKET NO. CONFIRMATION NO.
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`10/616,709 07/10/2003
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`Neil P. Desai
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`APPOI_COS_US
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`2620
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`66140
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`7590
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`BLANCHARD & ASSOCIATES
`566 WEST ADAMS STREET
`SUTTE600
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`CHICAGO, IL 60661
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`07/13/2012
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`EXAMINER
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`TELLER, ROYR
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`ART UNIT
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`PAl>t::R NUMBEl{
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`16.54
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`MA1L DATE
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`DELIVERY MODE
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`07/13/2012 PAPER
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`Please find below and/or attached an Office communication concerning this applicatiol!l or proceeding.
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`The time peiiod
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`for reply, if any, is set in the attached communication.
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`PTOL-90A (Rev. 04/07)
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`Bass and Spangenberg
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`v.
`Fresenius Kabi USA, LLC
`U.S. Patent No. 8,476,010
`Exhibit 1018
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`Exh. 1018
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`Office Action Summary
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`Application No.
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`10/616,709
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`Examiner
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`Applicant(s)
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`DESAI ET AL.
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`Art Unit
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`1654
`ROY TELLER
`•• The MAILING DATE of this communication appears on the cover sheet with the correspondence address ••
`Period for Reply
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE J. MONTH(S) OR THIRTY (30} DAYS,
`WHICHEVER IS LONGER, FROM THE MAILING DATE OF TH IS COMMUNICATION.
`Extensions of time may be available under 1he provisions of 37 CFR 1. 136(a). In no even1, however, may a reply be timely filed
`af1er SIX (6) MONTHS from the mailing date of 1his communication.
`If NO period for reply is specified! above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will. by statute. cause the application to become ABANDONED (35 U.S. C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
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`Status
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`1}1Z! Responsive to communication(s) filed on 29 March 2012.
`2a)D This action is FINAL.
`2b)l8! This action is non-final.
`3}0 An election was made by the applicant in response to a restriction requirement set forth during the interview on
`__ ;the restriction requirement and election have been incorporated into this action.
`4)0 Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parte Quayle, 1935 C. D. 11, 453 O.G. 213.
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`Disposition of Claims
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`5)!ZI Claim(s) 1-64.68.69 and 71-88 is/are pending in the application.
`5a) Of the above claim(s) __ isfare withdrawn from consideration.
`6)0 Claim(s) __ is/are allowed.
`7)1Z! Claim(s) 1-64. 68. 69. 71-88 is/are rejected.
`8)0 Claim(s) __ is/are objected to.
`9)0 Claim(s) __ are subject to restriction and/or election requirement.
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`Application Papers
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`1 0)0 The specification is objected to by the Examiner.
`11)0 The drawing(s} filed on __ is/are: a}O accepted or b}D objected to by the Examiner.
`Applicant may not re quest that a ny obj ect ion to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
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`Replacement drawing sheet (s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1 .121 (d).
`12)0 The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PT0-1 52.
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`Priority under 35 U.S.C. § 119
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`13)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`a)O All b)O Some * c)O None of:
`1.0 Certified copies of the priority documents have been received.
`2.0 Certified copies of the priority documents have been received in Application No. __ .
`3.0 Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`* See the attached de-tailed Office action for a list of the certified copies not received.
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`Attachment{s)
`1) [gl Notice o f References Cited {PT0-892)
`2) 0 Notice of Draftsperson's Patent Drawing Review (PT0-948)
`3) D Information Disclosure Statement(s) (PTO/SB/08)
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`Paper No(s)/Mail Date - -·
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`4) 0 Interview Summary (PT0-413)
`Paper No (s)/Mail Date. __ .
`5 ) 0 Notice of Informal Patent Application
`6) 0 Other: __ .
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`U.S. Patent and Trad~•nark Ofhce
`PTOL-326 (Rev. 03-11)
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`Office Action Summary
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`Part of Paper No./Mail Date 20120613
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`Exh. 1018
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`Application/Control Number: 10/616,709
`Art Unit: 1654
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`Page2
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`DETAILED ACTION
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`This office action is in response to Applicants' Pre-appeal Brief Request for Review filed
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`29 March 2012.
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`Based upon a Pre-Appeal Brief conference, prosecution has been reopened. The finality
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`of the previous Office action is withdrawn.
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`Claims 1-64, 68-69 and 71 -88 are under examination.
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`Response to Amendments/Arguments
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`Applicant's arguments and amendments filed 7/28/11 are acknowledged and have been
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`fully considered. Any rejection and/or objection not specifically addressed are herein
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`withdrawn.
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`Claim Rejections - 35 USC§ 103
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`The following is a quotation of 35 U.S.C. l03(a) which fo1ms the basis for all
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`obviousness rejections set forth in this Office action:
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`(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in
`section 102 of this title, if the differences between the subject matter sought to be patented and the prior att are
`s uch that the subject matter as a whole would have been obvious at the time the invention was made to a person
`having ordinary skill in the art to which said subject matter pertains. Patentabili.ty shall not be negatived by the
`manner in which the invention was made.
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`Claims 1-64, 68-69 and 71-88 are rejected under 35 U.S.C. 103(a) as being unpatentable
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`over Zhang et al. (USPN 6,399,087) in view of Lundgren et al. (USPN 6,576,245) and Sautou-
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`Miranda et al. (International J oumal of Phrumaceutics, 1996, 130, pp-251-255) and Desai et al
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`(USPN 5,916,596).
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`Exh. 1018
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`Application/Control Number: 10/616,709
`Art Unit: 1654
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`Page 3
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`The instant invention is drawn to a stelile pha1maceutical composition for parenteral
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`administration of propofol, wherein said composition is stored in a container having a closure
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`wherein said closure is inert to propofol, wherein the composition comprises:
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`a) about 0.5% to 10% by weight 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%,
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`g) pH between 5.0-8.5,
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`and when the composition in the container sealed with the closure is agitated at a
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`frequency of 300-400 cycles/minute for 16 hours at room temperature, the composition
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`maintains a propofol concentration measured by HPLC that is at least 93% of the starting
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`concentration of the propofol.
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`Zhang et al. discloses a stetile phmmaceutical composition for parenteral administration
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`of propofol, wherein the composition comprises :
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`a) about 1% to 2% by weight 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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`Exh. 1018
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`Application/Control Number: 10/616,709
`Art Unit: 1654
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`g) pH between 5.0-7.5.
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`Page 4
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`See, i.e., for example, absb:act, column 3, lines 21-22, claims l-14.
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`Zhang does not disclose a container having a closure wherein said closure is ineti to
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`propofol, nor a protein in the propofol emulsion.
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`Lundgren et al. discloses a primary package containing low molecular weight peptide-
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`based thrombin inhibitors which package is sealed with a tubber stopper or plunger containing
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`bromobutyl rubber. Lundgren discloses the preferred low molecular weight peptide based
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`thrombin inhibitor be kept in glass vials or syringes. See, i.e., for example, abstract, column 2,
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`lines 1-2, claims 1-5.
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`Sautou-Miranda et al. discloses propofol stored in glass and polypropylene containers for
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`30 days with little lose of potency. See, for example, abstract, and page 255.
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`Desai et al. discloses in vivo delivery of phrumacologically active agents, such as
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`propofol, where protein is added to act as a stabilizing agent for the f01mation of stable
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`nanodropJets. Protein is added at a concentration in the range of about 0.5%-5% (w/v). An
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`emulsion is then f01med. Desai discloses the formation of nanopruiicles, pariicles which are less
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`than 200 nanometers in diameter. Desai discloses solvents used to dissolve a pharmacologically
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`active agent, such as soybean oil, coconut oil, olive oil, safflower oil, cotton seed oil, sesame oil,
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`orange oil, limonene oil, Cl-C20 alcohols, C2-C20 esters, C3-C20 ketones, polyethylene
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`glycols, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons and
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`combinations thereof. See, for example, entire reference, especially abstract, column 9, lines 1-
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`13, lines 21-23, line 26, lines 59-60, column 10, lines 36-37, column 11, line 21, lines 35-36.
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`Exh. 1018
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`

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`Application/Control Number: 10/616,709
`Art Unit: 1654
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`PageS
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`It would have been prima facie obvious to one of ordinary skill in the art at the time the
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`invention was made to have combined the composition of Zhang with the beneficial teachings of
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`Lundgren because Lundgren discloses the a low molecular weight package sealed with
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`bromobutyl rubber. The brombuty] rubber would inherently work for a. low molecular weight
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`(below 1,000 M.W.) composition such as propofol (M.W. - 178.27). Further, Sautou-Miranda
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`disclosure of propofol stored in glass and polypropylene containers for 30 days with little lose of
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`potency beneficially teaches a composition of propofol comprising a container which is inett to
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`propofol. It would be obvious to put any known pharmaceutical composition within that type of
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`sealed container-for well known sterility, stability and transport purposes. Sautou-Miranda
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`disclosure of propofol stored in glass and polypropylene containers for 30 days with little lose of
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`potency mimics the outcome of the instant claims composition that maintains a propofol
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`concentration that is at least 93% of the stmting concentration of propofol. Fmther, Desai
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`discloses a propofol-protein emulsion wherein microdroplets of less than 200 nanometers are
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`fo1med, as well as solvents used to dissolve a phaJmacologically active agent, such as propofol.
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`Applicant's arguments as they pettain to the mt rejection above have been carefully
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`considered but were not found persuasive. Applicant contends that the office action does not
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`provide a factual basis or reasoning for predicatably combining the teaching of the cited art
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`references. Further, with regards to an emulsion including an oil phase that includes propofol, an
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`aqueous phase and a stabilizing layer for the oil phase that includes a smfactant and a protein,
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`and well as the recited rnicrodroplets and an injectable canier, where the microdroplets contain
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`propofol spheres SUJrrounded by a layer that includes a phospholipid but that does not include an
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`Exh. 1018
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`Application/Control Number: 10/616,709
`Art Unit: 1654
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`Page6
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`oil that can support bacterial growth, the elements are not discussed in the office action.
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`Applicant contends that the Zhang reference does not disclose any container at all for storing
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`propofol. Applicant futther contends that the cited reference fails to disclose claim limitations
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`relating to the container. However, the examiner contends that the Lundgren reference discloses
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`a primary package containing low molecular weight peptide-based thrombin inhibitors which
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`package is sealed with a rubber stopper or plunger containing bromobutyl rubber. Lundgren
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`discloses the preferred low molecular weight peptide based thrombin inhibitor be kept in glass
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`vials or syringes. The brombutyl rubber would inherently work for a low molecular weight
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`(below 1,000 M.W.) composition such as propofol (M.W. -178.27). Further, Sautou-Miranda
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`disclosure of propofol stored in glass and polypropylene containers for 30 days with little lose of
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`potency beneficially teaches a composition of propofol comprising a container which is inert to
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`propofol. The examiner further contends that with regards to an emulsion including an oil phase
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`that includes propofol, an aqueous phase, and a stabilizing layer for the oil phase that includes a
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`sutfactant and a protein, that Zhang discloses the elements as claimed in the pharmaceutical
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`composition. Futther, the examiner contends that the recited microdroplets and an injectable
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`carrier, where the microdroplets contain propofol spheres sutTounded by a layer that includes a
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`phospholipid but that does not include an oil that can suppott bacteti al growth, that Zhang
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`discloses phospholipid coated microdroplets of propofol with no soybean oil. See, for example,
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`column 2, lines 35-36. Futther, Desai discloses a propofol-protein emulsion wherein
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`microdroplets of less than 200 nanometers are formed.
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`Exh. 1018
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`Application/Control Number: 10/616,709
`Art Unit: 1654
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`Page 7
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`Conclusion
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`All claims are rejected.
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`Any inquiry conceming this communication or earlier communications from the
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`examiner should be directed to Roy Teller whose telephone number is 571-272-0971. The
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`examiner can normally be reached on Monday-Friday from 5:30 am to 2:00 pm ..
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
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`supervisor, Cecilia Tsang, can be reached on 571-272-0562. The fax phone number for the
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`organization where this application or proceeding is assigned is 571-273-8300.
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`Information regarding the status of an application may be obtained from the Patent
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`Application Inf01mation Retrieval (PAIR) system. Status inf01mation for published applications
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`may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
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`applications is available through Piivate PAIR only. For more information about the PAIR
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`system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
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`system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-fi·ee).
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`/Roy Teller/
`Examiner, Art Unit 1654
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`/Ch1istopher R Tate/
`Primary Examiner, A1t Unit 1655
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`Exh. 1018