Atty. Dkt. No. 080618-0716
`Appl. No. 12/591,200
`
`IN THE UNITED STATES PATENT AND TRADE~fARK OFFICE
`
`Appl.icant:
`
`Horst OLSCHEWSKI et al.
`
`Title:
`
`TREPROSTINIL ADMINISTRATION BY INHALATION
`
`Appl. No.:
`
`12/591 ,200
`
`Filing Date:
`
`11112/2009
`
`Examiner:
`
`Sara Elizabeth Townsley
`
`A1t Unit:
`
`1629
`
`Confinnation
`
`4093
`
`Number:
`
`DECLARATION UNDER 37 C.F.R. § 1.132 OF DR. EDMUND J . ELDER, JR.
`
`l, Dr. Edmund J. Elder, Jr., hereby declare:
`
`I.
`
`l hold a Ph.D. in Pharmaceutical Sciences and a B.S. in Pbannacy from the Medical
`
`University of South Carol ina. I currently serve as the Director of Zeeh Pharmaceutical
`
`Experiment Station and a lecturer in both the School of Pharmacy and t11e School of
`
`M:edicine and Public Healtb at the University of \Visconsin-Madison. See EXHIBIT .1.
`
`2.
`
`My work focuses on drug development, including formulation and physiocbemical
`
`characterization of compounds. My CV, vvhich is attached as EXHIBIT 1, lists my
`
`publications.
`
`3.
`
`I am a paid consultant for United Therapeutics, the assignee of tbe above-identified
`
`patent application, in connection with this matter. My compensation is in no way
`
`dependent on the content of my opinions or the disposition of this application.
`
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`4.
`
`To the best of my knov.'le<lge, I have not received any prior research funding or other
`
`compensation from United Therapeutics.
`
`I.
`
`The Cited References
`
`5.
`
`I am familiar with the Office Action dated October 10, 2014 in U.S. Patent Apphication
`
`No. 12/591,200, as well as the disclosure and claims of the subject application. I am also
`
`familiar with the references cited in the Office Action and the response filed November 9,
`
`2015.
`
`6.
`
`I understand the Claims of U .S. Patent Application No. 12/591,200 are directed to a
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`method of treating pulmonary hypertension comprising: administering by inhalation to a
`
`human in need thereof a therapeutically effective single event dose of an inhalable
`
`fonnulation witb a pulsed. ultrasonic nebulizer, wherein said therapeutically effective
`
`single event dose comprises from I 5 µg to 90 µg of tJeprostinil or a pharmaceutically
`
`acceptable salt thereof, said therapeutically effective single event dose is inhaled in 18 or
`
`less breaths by the human.
`
`7.
`
`l have revjewed US 2004/0265238 (Chaudry) and U .S. Patent No. 6,357,671 (Cewers)
`
`cited in the Office Action, in addition to further references pertinent in the art -
`
`specifically tl1ose references mentioned below and attached as EXHIBITS 2-6.
`
`IJ.
`
`Single Event Oose
`
`8.
`
`At the time the '200 application was filed, the .. single event dose" featured in the pending
`
`claims is recognized as depending on two parameters: (1) the concentration of the
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`treprostirul inhalation formulation prior to aerosolization; and (2) the total amount
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`(weight or volume) of tbe formulation delivered through tbe single inhalation event
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`("delivered weight" or "delivered volume"). See, e.g., "Guidance for Industry: Nasal
`
`Spray and Inhalation Solution, Suspension, and Spray Drng Products - Chemistry,
`
`Manufacturing, and Controls Documentation" (Exhibit 2) on page 38, stating that:
`
`The medication dose delivered to the patient should be expressed by a
`statement in this section, such as: Each spray delivers 'x' mcg of drug
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`substance in 'w' mg of suspension or solution equivalent to 'y' mcg of drug
`substance base. (if applicable) from the nasal actuator or mouthpiece. The term
`approximately should not be used to modify the medication dose delivered.
`
`9.
`
`According to the Office Action, the guidance allegedly provided by Chaudry regarding
`
`single event dose is found in prophetic example 4, reproduced below in its entirety:
`
`Example4
`(0097]
`5 Treprostinil sodium 0.1 - 10.0 mg/ml Sodium Chloride 2.0-l 0.0 mg/ml
`Sodium Hydroxide q.s. Citric Acid q.s. Water q.s.
`(0098] Example 4 is a prophetic example of a formulation comprising the
`vasodilator epoprostenol [sic: treprostinil]. Sodium chloride may be added to
`the solution to adjust tonicity, and sodium hydroxide and ciu·ic acid are added
`to adjust the pH of the solution. The solution of Example 4 may be made by
`methods known to tbose of ordinary skill in tbe art.
`
`to.
`
`This prophetic example gives a range of tJeprostinil concentration that varies 100-fold
`
`with the lowest concentration set at 0.1 mg/mL, i.e. 100 µg/mL, and increasing to 10
`
`mglmL. Such a wide dosing range is consistent with the prophetic nature of the example,
`
`and does little to provide guidance to one of skill in the art if attempting to determine a
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`"single event dose" for the treprostinil formulation in Example 4 .
`
`11. With respect to the total amount (weight or volume) of the formulation delivered through
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`the single event ("delivered weight" or "delivered volume"), the "delivered volttme" of
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`an inhalable formulation delivered through a single inhalation event by a nebulizer
`
`system is rncognized as depending on a number of factors. Those factors include the
`
`initial volume of the fonnulation, i.e., the "fill volume," and the residual volume of the
`
`formulation that cannot be further delivered through the nebulizer, i.e., the "dead
`
`volume" (or "residual volume"). See, e.g. "European Respiratory Society Guidelines on
`
`the use of nebulize.rs: Guidelines prepared by a Eu.ropean Respiratory Society Task Force
`
`on tbe use of nebulizers" (Exhibit 3) in the paragraph bridging pages 230-231 , stating
`
`that
`
`Impmtant factors influencing the total dose delivered to a patient's airways
`include the initial. volume fill, the efficiency by which nebulized aerosol is
`made available for patient inhalation, and the amount of residual or ''dead"
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`volume left in the nebulizer on cessation of operation ... Nebulization therapy
`usually continues until the volume left in the nebulizer is so low that the
`nebulizer ceases to function continuously and begins to "sputter". This volume
`is typically - 1 mL, but may be as low as 0.5 mL or as bigh as 1.5 mL. The
`amount left is very bigb compared to a typical volume fill (e.g. 2.5 rnL).
`
`12.
`
`Accordingly, the "delivered volume" corresponds to the difference between the " dead
`
`volume" and the "fill volume". In other words, both the "dead volume" and the "fill
`
`volume" are needed to assess the volume of the formulation delivered thrnugb a single
`
`event inhalation.
`
`13.
`
`Tmning to Chaudry' s specification, paragraph [000 l ]-[0059] and paragraphs [0067)(cid:173)
`
`(0099) of Chal1d1y do not describe "dead volume" or "fill volnme."
`
`14.
`
`Chaudry's paragraph [0060) describes "fill volume" in the form of a laundry list
`
`containing alternative ranges or values ("In another alternative embodiment, tbe system
`
`of the present invention comprises one or more dispensing containers prefilled with about
`
`0.1 to about 5.0 ml, or about 0.5 ml to about 5.0 m l, or about 1.0 ml to about 5.0 ml; or
`
`about 0.1 ml to about 3.0 m l, or about 0.1 ml to about 2.0 1111, or about 0.5 ml to about 2.0
`
`ml, or about I ml, or about l .5 ml, or about 2.0 m l, or about 2.5 ml, or about 3 .0 ml, or
`
`about 3.5 ml, or about 4.0 ml, or about 4.5 ml, or about 5.0 ml, or about O. l ml to about
`
`2.25 ml, or about 1.0 ml to about 2.0 ml, or about 2.0 ml to about 2.4 ml of a premixed,
`
`premeasured, aqueous inhalation solution comprising a single unit dose of a
`
`therapentically effective amount of one or more pulmonary hypertension reducing
`
`agents"). Nothing in Cbaudry's paragraph [0060) describes the corresponding "dead
`
`volume" of any of the alternative ranges or values of the "fill volwne."
`
`15.
`
`Cbaud.ty's paragraph [0062] also describes " fill volume" in the form of a laundry list
`
`containing alternative ranges or values (" In one alternative embodiment, the volume of
`
`the one or more pulmonary hypertension re.ducing agents inhalation solutions of the
`
`present invention is about 0.1 ml to about 2.25 ml, or about 0. I ml to about 2 ml, or about
`
`1 ml to about 2 ml, or about 1.5 ml to about 2 ml, preferably about 1 ml, about 1.5 ml,
`
`about 2.0 ml, or about 2.2.5 ml"). Nothing in Chaudry's paragraph [0062] describes the
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`corresponding "dead volume" of any of the alternative ranges or values of the "fill
`
`vol.ume."
`
`I 6.
`
`Cbaudry's paragraph [0066] describes "fill volume" in the form of a broad hypothetical
`
`range (emphasis supplied): " ... It is believed that administering about 0.1 ml to about
`
`2.0 ml fill volume of an inhalation solution into a nebulizer, for example, will optimize
`
`the therapeutjc effect of the individual's deep inspiration efforts dmfog treatment, and
`
`will optimize the therapeutic effect of tbe individ11al's breath-holding efforts as well."
`
`Nothing in Chaudry's paragraph [0066] describes the corresponding "dead volume" of
`
`the broad hypothetical range of "fill volume!'
`
`17.
`
`Cbaudry's paragraph [0065) describes "dead volume" also in the form of a laundry list of
`
`alternative ranges (emphasis supplied): " ... Less solution remaining in the nebulizer
`
`system means more medication (e.g., one or more pulmonary hypertension reducing
`
`agents) administered to tbe individ1ial during each tTeatmeut. Iu oue alternative
`
`embodiment, the amonnt of solution remaining in the nebu1izer system after each
`
`treatment mav be less than 0.50 ml. or less than 0.30 ml, or less than 0.20 ml or less than
`
`0.10 ml or less than 0.05 ml of the one or more pulmonary hypertension reducing agents
`
`inhalation solutions of the present invention, e.g. an inhalation solution comprising 2.5
`
`mg albutero1and0.5 mg ipratropium bromide." Nothing in Chaudry's paragraph [0065]
`
`describes tbe corresponding "fill volume" of any of the alternative hypothetical -ranges of
`
`the "dead volume." Chaudry' s description of tbe "fill volume" in paragraphs [0060],
`
`[0062], and [0066], and Chaudry's description of the "dead volume" in paragraph [0065),
`
`are insufficient to allow reasonable assessment of the " delivered volume" of the
`
`formulation in a single event inhalation, especially in light of the many alternative ranges
`
`provided in those disconnected paragraphs. Indeed, the combination of certain values
`
`selected from the "fill volume" and "dead volume" paragraphs results in a negative
`
`volume, which would be undeliverable.
`
`18.
`
`Paragraph [0064] of Chaudry specifically describes both "dead volume" and "fill
`
`volume" of the nebul.izing device:
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`For example, when nebulizing an inhalation solution comprising 2.5 ml or
`more, about 0. 7 ml of the solution remains in the nebulizer system after
`treatnient, though the amount may vary depending on the model of tJ1e
`nebulizer used. In these i.Jlstances, the individual is not receiving the
`prescribed dosaae or optimum dosage of inhalation medication.
`
`19.
`
`Chaud1y' s paragraph [0064] describes a problem of nebulizing devices in general(cid:173)
`
`insufficient delivery of fonnulation per inhalation event because of the dead volume.
`
`Moreover, one of ordinaxy skill in the mt would undersland from paragraph [0064] that a
`
`delivery volume of 1.8 mL (2.5 mL fill volume·- 0. 7 mL dead volume) would lead to the
`
`individual "not receiving the prescribed dosage or optimum dosage of inhalation
`
`medication," in.eluding its exemplary formulations (e.g., prophetic example 4) containing
`
`at least 0.1 mg/mL, i.e. 100 µg/mL, of treprostinil.
`
`20.
`
`The insufficiency or inadequacy of 1.8 mL delivery volume is reconfinned by Cbaudry
`
`toward the end of paragraph [0064], stating that (emphasis supplied):
`
`For example, in one day, due to the residual medication remaining in the
`.nebu!izer system after each treatment, an .individual fails to rece.ive
`approximately 2.1 ml, or more of the prescribed daily amount of medication.
`
`21.
`
`Chm.1d1y purpo1tedly solves the problem by adjusting filling volume to reduce the dead
`
`volume with tbe ultimate effect of delivering more drug than conventional nebulizers,
`
`stating in paragraph [0065] that (emphasis supplied):
`
`It is believed that tbe fill volumes of the one or more pulmonary hypertension
`.redticing agents .inhalation solutions of the present invent.ion w.ill result in
`lesser amounts of solution remaininQ in the nebulizer svstem after treatment.
`Vi-'hen compared to conventional inhalation solutions (e.g. 2.5 ml or 3 ml fill
`volume). Less solution remaining in the nebulizer svstem means more
`medication (e.~ .. one or more pulmonary hypertension reducing agents)
`administered to t11e individual during each treatment.
`
`22.
`
`Taken together, Cbaudry specifically teaches the amount of medication delivered per
`
`nebulizing event as being greater than a conventional nebulizer, e.g. at least greater than
`
`the 1.8 mL delivery volume described in paragraph [0064). ·with t11e lower limit. of
`
`treprostinil concentration io Chaudry being 100 µg/mL, tbe si11gle event dose in Cbaudry
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`would be at least 180 ~Lg oftreprostinil, which is at least two times the upper limit of the
`
`single event dose featured in the pending claims, "from 15 µg to 90 µg" in claim 18.
`
`III.
`
`" 18 or less breaths"
`
`23.
`
`The "18 or less breatbs" featured in the pending claims corresponds to an inhalation time
`of at least less than a few minutes. See, e.g. "Ganong's Review of Medical Physiology-
`
`23rd Ed" (Exhibit 4 on pa~600. describing 30 breaths per minute as "raQid shallow
`
`breathing" and 10 breaths er minute as "slow deep breathing."
`
`~~..;~'\.-.; , :..$.111
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`T ~~t.f ~:t)~-~ E:ff~u:t of \':.Ml~tfuin~ hl' t~§<t.-,;frato:rv
`l'.l.lt:~ au<.idg.ptfi-;0n. ~lw.~~~r ~~~i1tll~t~!ml.
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`lt."S~ tba~ ~h~re~i~l:raU.~n' tnlmitQ vti~tm'.~e. _Nate m atlil.Uk~ri. dim .
`ooa.m~ 0f th~ .. ~il:. ip~"t;; n11~~& ~~'1:Il~:n.v b.r:~[hfog pro<ltK~~
`·~~'"'''I,.. ~,,,." .,.;~~""~l-«:y. '"-~'>'lt'>-i~"H"'r ·~;!:.,_,~~.- .• ,-1.,.,. :·. <t·" "1'-·i;..."""'"t,~ S:'~<'>: "'°' ·~~<> .
`. t'·M'.h~·:t:J. J.~;.,,~~· ·~*:~. ~"}.,~~~~t. :'l'~\;":;:.;:~.~X{.~~-~t::\,,~~l x:J:~AA:s~ .. ~~l~~ ·~~.~·~·l·~"H.~.~~);;(:J:.::o.u.;J;:~ ~:t. Ru~~.
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`
`24.
`
`Turning to Cbaudry's spedfication, paragraphs [OOOJ ]-[0062] aod paragraphs [0068](cid:173)
`
`[0099] of Chaudry do not describe the duration of a single inhalation event.
`
`25.
`
`According to the outstauding Office Action, the guidance allegedly provided by Cbaudry
`
`regarding the single event inhalation time is found in paragraph [0063], stating that:
`
`In one alternative embodiment, the above fill volumes of t11e present invention
`may reduce the tiroe of each nebulization treatment by at least 20%, 30%, 40%.
`50%, 60%, 70% or 80% or more over conventional nebulizer treatments (e.g. 2.5
`m1 or 3 ml fill volume). In another alternative embodiment, the fill volumes of the
`present invention may reduce each nebulization treatment to about 12, I 0, 9, 8, 6,
`5, 4, 3 minutes, or less over conventional nebulizer treatments (e.g. 2.5 ml or 3.0
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`ml fill volume). Reducing the amount of time to complete the treatment means
`individuals will be more likely to comply with the prescribed dosing regimen and
`achieve optimal benefit from the medication prescribed.
`
`26.
`
`The first sentence of Chau dry' s paragraph [0063] describes percentage reduction of
`
`inhalation time compared to that of a conventional nebulization treatment. Without
`
`k11ovving tl1e value of the duration of conventional in.halation time or which of the various
`
`concentrations, fill volumes, dead volumes are to be used, one of ordinary skill in the art
`
`would not be able to assess the actual reduced inhalation time described in the first
`
`sentence of paragraph [0063]. Chaudry, thus, offers a possible outcome .. _ reduction of
`
`inhalation time - without gu.idance on which variables need to be adjusted to achieve the
`
`result lnsiead, Chaudry provides a variety of possible pennutatious and combinations of
`
`variables, leav ing one of ordinary skill in the art witb no starting point from which to
`
`determine bow to achieve a specific outcome.
`
`27.
`
`1n my opinion, the second sentence of Chaud.ry's paragraph [0063] refers to the following
`
`two alternative embodiments: (l) reduce eacb nebulization treatment to "about 12, 10, 9,
`
`8, 6. 5, 4, 3 minutes", or (2) reduce each nebulization treatment to "less over conventional
`
`nebulizer treatments." This interpretation is consistent with the rest of Chaudry's
`
`disclosure of regarding treatment time. See, e.g., Chaudry's paragraph [0067], stating
`
`that:
`
`. .. The individual continues breathing into the mouthpiece or fac.emask m1til
`the nebulization treatment is finished. This may take about 12. l l. 10. 9. 8. 7.
`6. 5, 4 or 3 minutes. In an alternative embodiment, the nebulization treatment
`is finished when at least substantially all the mist is removed from the
`nebulizer chamber. This may take about 12, l l, 10, 9. 8, 7, 6, 5, 4, or 3
`minutes ...
`
`28.
`
`The Office appears to interpret the "or less" in Cbaudry's paragraph (0063) as a
`
`continuation of "3 minutes", i.e., referring to "less than 3 minutes" of nebulizing
`
`treatment. time. Cn.der this interpretation~ however, tbe "12, lO, 9, 8, 6, 5, 4, 3 minutes, or
`
`less" wonld then refer not to the inhalation time i.tself, but to a comparative value
`
`reflecting the difference bet".:et~n Chaudry's inhalation time and the conventional
`
`in1ialation time. In other words, the second sentence of paragraph [0063] would be
`
`interpreted as describing the alternative embodiment in which the fill volumes of the
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`present invention may reduce each nebulization treatment to about 'x' minutes oyer
`
`fQgv_e11JiQ!!~l11~lrnJi~~L11:.~!1.!!'!}~m~. Without knO\ving rbe value of the duration of
`
`conventional inhalation time, one of ordinary skill in the art V\iould not be able to assess
`
`what tbe reduced inbal.ation time is under the Office's interpretation of "or less'' in
`
`Chaudiy's paragraph [006'.l].
`
`29.
`
`h1 additiou, paragraph [0063) of Chaudry at best J)fOvides: {l) a description of reduced
`
`inhalation time that is gen.em! i11 nature (further generic/non-belpful prophetic teachings),
`
`and (2) the purported benefit for the reduced inhalation time is to improve patient
`
`compliance as a genernl result of requiring less time for each inhalation event.
`
`30. Of course, a clinician in practice would only consider adopting a reduced single event
`inhalation time if the reduced inhalation time does not lead to significant side effects. In
`
`other words, a clinician in practice would not adopt the reduced inha'lation time taught in
`
`Chaudry to improve patient compliance if the reduced inhalation time of a specific active
`
`agent would Ukely lead to adverse side effects.
`
`31..
`
`This desire to avoid adverse events is important i11 the context of Chaudry. As stated on
`
`page 17 of the Gessler reference (Exhibit 5):
`
`·'tl1e inhalation time for delivery of an equivalem iloprosl dose at the
`
`mouthpiece (2.8 ~tg) was reduced from 12 min with the jct ncbulizcr system to 2 min
`witl1 the ultnlsonk ncbulizer, when retaining the same conce:ntration of the ilopr(>St
`solution (l 0 ~ig·mL'\ 'In preliminary c.:athercr invcstigatinns, however, some increase
`in systemic side effects \Vas observed when administering the total iloprost dose of
`
`2 8 ~1g. via the. inhalation route for s uch a short time period."
`
`32.
`
`Likewise, page 54 of the Voswinckel reference (Exhibit 6) also states that:
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`"A <lose of morn than 5 iig iloprest per inhalation or a reduction of inhalation time to
`
`less lhan 3 min induce.s in most patients considerable systemic prost~moid side dk;;ts
`
`like ])ypotension, dizziness, headache, jaw pain, nausea or (diarrhcaJ."
`
`33.
`
`Thus, in my opinion, a clinician in practice would be aware of the "considerable"
`
`systemic side effects of at least one of the specifically disclosed vasodilators (iloprost) if
`inhaled too quickly, e.g. " 2 min" described in Gessler or "less than 3 min" described in
`Voswinckel. Moreover, " iloprost" is listed side-by-side with "treprostinil" ·under the
`specifically recognized class of "prostacyclin analogs." See Chaudry's paragraph [0026),
`
`stating that:
`
`. .. V asodilators for use herein also include prostaglandins (Eicosanoids ),
`including prostacyclin (Epoprostenol) and prostacyclin analogs, including
`Iloprost and Treprostinil, and prodrugs, salts and isomers thereof. ..
`
`34.
`
`As such, a clinician in practice would not consider Chaudry's description of its single
`
`event inhalation time 1n paragraph [0063] as teaching toward "less than 3 minutes," at
`
`least not v;ihen the inhalable fonnulation contains iloprost or treprostinil. The specific
`
`teachings of Gessler and Vos.,vinckel would cause a clinician ill practice to avoid the
`
`shorter inhalation times allegedly disclosed by Cbaudry assuming the correctness of the
`
`Office's interpretation of Chaudty.
`
`35.
`
`I declare further that all statements made herein of my own knowledge are true and that
`
`all statements made on information and belief are believed to be trne; and funher that
`
`these statements \.Vere made with the knowledge that making of willful false statements
`
`and the like are punishable by fine or imprisonment, or both, under Section 100] of Title
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`Atty. Dkt. No. 080618-0716
`Appl. No. 12/591,200
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`18 of the United States Code and that such willfol statements may jeopardize the validity
`
`of the applications or any patent issuing thereon.
`
`tdmund J. Ekte~h.D., R.Ph.
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`7401 North Pass
`Madison, WI 53719
`{608) 497-0117
`edmund.elder@gmail.com
`
`EDUCATION:
`
`Edmund J. Elder, Jr., Ph.D., R.Ph.
`(Ed)
`
`University of Wisconsin-Madison
`School of Pharmacy
`Rennebohm Hall
`777 Highland Avenue
`Madison, WI 53705-2222
`(608) 890-1198
`edmund.elder@wisc.edu
`
`Medical University of South Carolina, Charleston, SC
`Ph.D., Pharmaceutical Sciences; November 1989
`Dissertation: Development of a Dry Coating Method for Formulating Sustained-Release Products
`B.S., Pharmacy; May 1985
`
`Clemson University, Clemson, SC
`Pre-Professional Studies, Pre-Pharmacy; 1980-1982
`
`EMPLOYMENT:
`
`University of Wisconsin-Madison
`School of Pharmacy
`Director, Zeeh Pharmaceutical Experiment Station, July 2007 - present
`Affiliate, Division of Pharmaceutical Sciences, February 2014 - present
`Associate Director, Zeeh Pharmaceutical Experiment station, April 2006 - June 2007
`School of Medicine and Public Health
`Senior Lecturer, Master of Science in Biotechnology Program, September 2013 - present
`
`Current Responsibilities
`• Key leadership position for providing laboratory services to UW and non-UW clients, including
`analytical, physical/chemical characterization (pre-formulation), and early-stage formulation services
`• Provide pharmaceutics expertise and chemistry, manufacturing and controls (CMC) knowledge to
`support pharmaceutical and biopharmaceutical development collaborations on and off campus
`• Advise and mentor Station staff
`• Apply project management and business development experience to enhance Station operational
`effectiveness
`• Share knowledge and expertise through Station participation in and sponsorship of educational
`programs addressing the process and science of drug development in collaboration with UW(cid:173)
`Madison, School of Pharmacy, Extension Services in Pharmacy (continuing education division)
`• Graduate Course Lectures
`- Introduction to Pharmaceutical Sciences - course introduction & formulation lectures
`- Biotechnology Operations - course co~coordinator, lectures on various aspects of biotech R&D
`
`The Dow Chemical Company, Midland Ml
`Dowpharmas1.~
`Global Pharmaceutical Development Director I Applications Development Leader, April 2004 - April 2006
`Pharmaceutical Technologies Group
`Pharmaceutics Director I Technical Leader, August 2000 - April 2004
`
`Prior Responsibilities
`• Co-leader (with commercial leader), new business development: BioAqueoussM Solubilization Services
`• Oversight of multi-departmental technical activities for development of a drug delivery service offering
`including interfacial sciences, engineering, analytical, toxicology, intellectual capital management,
`licensing, manufacturing, project management, technical service and QA/regulatory
`• Lead external technology development collaborations and alliances including a multi-year
`university research program
`• Represent technical program during client interactions for commercial development activities
`• Provide pharmaceutics expertise for various emerging corporate growth opportunities
`• Serve as a mentor for potential future leadership staff through formal corporate program
`
`™Service Mark of The Dow Chemical Company
`
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`page 2
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`Ed Elder. Jr.
`
`Glaxo I Glaxo Wellcome (now GlaxoSmithKline), Research Triangle Park, NC
`Pharmaceutical Sciences
`Sr. Group Leader, Formulation and Process Development, November 1997 - August 2000
`Group Leader, Formulation Development, February 1997 - November 1997
`Process Science and Technology
`Research Leader, Liquids Process Development, September 1995- February 1997
`Research Leader, Pharmaceutical Technology Development, July 1994 - August 1995
`Research Investigator. May 1992 - June 1994
`Senior Scientist, September 1989 - April 1992
`
`Previous Experience
`• Management: Group of ten formulation and process development scientists, covering al! dosage
`forms, mentoring of new CMC team leaders, department management team and division leadership
`committees
`• Project Management: Chemistry manufacturing & controls (CMC) matrix team leader
`- Responsible for oversight of all cross-functional CMC activities for multiple development programs
`- Represented GMC interests on international product development teams
`- Lead technology transfer and manufacturing site new product implementation teams.
`- Key R&D contact for FDA pre-approval inspections of domestic and foreign contract manufacturing
`sites.
`• Fonnulation and process development, optimization and scale-up using statistical experimental design
`• Primary interface with external development and manufacturing sites for new dosage form
`technologies including: soft gelatin capsules, effervescent products, and sterile products blow-fill-seal
`technology
`
`Burroughs Wellcome Company (now GlaxoSmithKline), Greenville, NC
`Pharmaceutical Research and Development Laboratory
`Pharmaceutics Graduate Student Fellow, June 1986 - August 1986
`
`Family Pharmaceuticals of America, Inc., Mt. Pleasant, SC
`Mail-service and retail pharmacy, acquired by Medi-Mail, Inc. in 1994, subsequently acquired by Bergen
`Brunswig Corporation, now AmerisourceBergen Corporation
`Minor Partner, subchapter-S corporation, January 1987 -June 1994
`Part-time Pharmacist, June 1985 - August 1989
`Pharmacy Intern, May 1983 - June 1985
`
`PROFESSIONAL ACHIEVEMENTS:
`
`68 Scientific Presentations ( 17 invited)
`8 Publications and 3 book chapters
`182 Short Course presentations (all invited), additional 17 presented at pharmaceutical companies
`The Visiting Scientist Program for Schools of Pharmacy and Pharmaceutical Scientists
`- Presented lectures/seminars at 14 schools/colleges of Pharmacy, 1993 - 2005
`Guest Lecturer
`- University of Wisconsin-Madison, Department of Pharmaceutical Sciences, 2006 - 2013
`- South Carolina College of Pharmacy, MUSC Campus, 2007
`- Medical University of South Carolina, Department of Pharmaceutical Sciences. 1991 - 1999
`- University of Texas at Austin, College of Pharmacy, 2001 - 2006
`- Michigan State University, ISPE Student Chapter, 2004
`- Virginia Commonwealth University/Medical College of Virginia, School of Pharmacy, 1997
`Grant Review Panels
`National Institutes of Health, National Institute on Drug Abuse, Special Emphasis Review Panel for
`Abuse-Resistant and Abuse-Deterrent Drug and Devices, 2014
`University of Minnesota, Center for Nanostructure Applications. 2007, 2008
`National Science Foundation. Office of Industrial Innovation. Small Business Innovation
`Research/Technology Transfer, SBIR/STTR Phase I. Food Safety, Drug, and Nutraceutical
`Manufacturing Panel. 2006
`
`December 2015
`
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`page 3
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`LICENSURE:
`
`South Carolina Pharmacist License, 1985 - present
`Wisconsin Pharmacist License, 2010 - present
`
`Ed Elder. Jr.
`
`PROFESSIONAL MEMBERSHIP/ACTIVITIES/AWARDS
`United States Pharmacopeia (USP)
`2015-2020 and 2010-2015 Compounding Expert Committee
`Award for Outstanding Contribution to the USP Standards-setting Process (committee}, 2013
`American Association of Pharmaceutical Scientists (AAPS). 1990-present (student member 1987-1989)
`Annual Meeting paper screener 1994 - 2000, 2006 - 2009, 2011 , 2013, 2015
`Co-Chair 2004 Annual Meeting Short Course, Particle Engineering Technologies: Theory and Practice
`Moderator (PT Podium Session: Pharmaceutical Processing and Scale-up), Tenth Annual Meeting
`and Expos ~tion, Miami Beach, FL, 1995
`Planning Committee and Moderator (PT Section), 1995 Southeast Regional Meeting, RTP. NC
`AAPS Appreciation Award - Co-Chair, 1994 Southeast Regional Meeting, Durham, NC
`European Federation for Pharmaceutical Sciences (EUFEPS), member 2003 - present
`Sigma Xi, The Scientific Research Society, member 1988- present
`Editorial Advisory Board
`Drug Development and Industrial Pharmacy, 2006 - present
`Journal Article Reviewer
`AAPS PharmSciTech, 2015
`Biopharmaceutics & Drug Disposition, 2012
`Drug Development and Industrial Pharmacy, 2000 - present
`Drugs in R&D, 2012, 2013
`European Journal of Pharmaceutics and Biop/1armaceutics, 2007, 2010, 2011
`International Journal of Pharmaceutics, 2007, 2009 - present
`Journal of Biomedical Nanotechnology, 2006 (Special Issue: Nanotechnology in Advanced Drug Delivery)
`Journal of Drug Delivery Science & Technology, 2008
`Journal of P/1armacy & Pharmacology, 2009, 2011
`Pharmaceutical Research, 2008
`University of Wisconsin- Madison. Pharmacy Professional Development, Industry Courses
`Applied Drug Development I (CMC introduction) Short Course, 2008-2010, On-line Short Course, 2015
`Applied Drug Development II (pre-formulation) Short Course, 2007-present
`Applied Drug Development Ill (formulation) Short Course. 2008-present
`CMC Project Team Leader Short Course, 2010-present
`Land O'Lakes June R&D Conference, planning committee 2008-present, chair 2013
`Extension Services in Pharmacy Appreciation Award - Chair, 2013 June Land O'Lakes
`Nanoparticles Short Course, 2007-2008
`Medical University of South Carolina {MUSC)
`Life Member, MUSC Alumni Association
`The Rho Chi Society {Pharmacy Honorary), College of Pharmacy, 1987
`Roche Pharmacy Communications Award. College of Pharmacy, 1985
`McKesson Presidential Award, College of Pharmacy, 1985
`ISPE Award for Out