IN THE UNITED STATES PATEI\"T AND TRAQEMARK OFFICE
`
`In reApplication of: Supriya GUPTA et al.
`
`Examiner: Lindsey Bcckhardt
`
`Applkation No.: 111788,076
`
`TC/ArC Unit: 4121
`
`Confirmation No.: 4752
`
`Filed: April 18, 2007
`
`Title: Pre-mixed, Ready to Use Pharmaceutical Compositions
`
`Attorney Docket Number: 19015-63
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`DECLARATION UNDER 37 C.F.R. §1.132 BY DR. HARRY G. BRITT AlN
`
`Sir,
`
`1, Dr. Harry G. Brittain, declare as follows:
`
`1.
`
`2.
`
`3.
`
`My education includes a B.A. in Chemistry from Queens College, awarded in
`1970; a M.A. in Physical Chern isty from Queens College ( 1972). and a Ph.D.
`in Physical Chemistry from City University ofNew York, awarded in 1975.
`
`I am presently the Institute Director of the Center for Pharmaceutical Physics
`and have held this position since 1999. My responsibilities include
`consultation in all areas of pharmaceutical physics and physical pharmacy.
`including prcformulation, formulation design, and product charactcri:lation.
`
`I have held numerous positions in pharmaceutical development, including
`Vice President of Pharmaceutical Development of Discovery Laboratories,
`Inc ( 1996-1999) where l was responsible for the design, formulation and
`development ()fall new products; Director of Pharmaceutical, Analytical and
`Chemical Development at Ohmeda Pharmaceutical Products Division (1994-
`1996) where I coordinated the development of injectable products; and
`llristol-Myers Squibb Pharmaceutical Research Institute (1985-1994) where [
`held various positions in tbrmulation research and development.
`
`Sandoz Exhibit 1009 Page 1
`
`

`

`Appl. No. 1117~&,07n
`Declaration Under 37 C.F.R. §1.132 by Dr. Harry G. Brittain
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`My academic experience includes positions at Rutgers University; Lehigh
`University; Seton Hall University; Ferrum College; and the lJniversity of
`Virginia.
`
`1 have numerous awards, editorial responsibilities, publications and patents.
`My full curriculum vitae is attached as l:xhibit A.
`
`I have read U.S. Patent Application Serial No. 2007/0249689 to Duncan ct al.
`entitled "Pre-mixed, Ready-to-Use Phannaceutical Compositions". I have
`also read the Office Action dated April 10,2009, the McFarlane reference,
`and the other references cited in the Office Action. The McFarlane reference
`describes a nicardipine hydrochloride concentrated formulation that requires
`reconstitution prior to administration. By contrast, I note that the ready-to-usc
`aqueous nicardipinc hydrochloride formulation of the present invention docs
`not require reconstitution and is indicated to be stable for an extended period
`of time.
`
`It is my understanding that the claims of the present application have been·
`amended without prejudice to include independent claims 40-51. My
`declaration will address these claims.
`
`As further discussed below, it is my technical opinion that the ready-to-use
`aqueous nicardipine hydrochloride fonnuJation compositions of the present
`invention are novel and unobvious in view of the prior art for reasons
`including:
`
`(i) one of ordinary skill in the formulation art would have had no
`expectation of success in formulating a stable form of a low concentration
`drug as presently claimed;
`(ii) the prior art of record in the case teaches away from certain
`embodiments ofthe invention; and
`{iii) the present invention meets a long felt need in the art.
`
`Benefits Of The Present Invention
`
`9.
`
`I 0.
`
`Nicardipine hydrochloride is a calcium channel blocker and based on its FDA
`approved labeling is indicated for the treatment of acute elevations of
`hypertension.
`
`I am advised that prior to the filing date of the present application, injectable
`nicardipine hydrochloride was commercially available solely in a concentrated
`form, being first approved by the FDA in 1992. The concentrate formulation
`is packaged in a glass ampule and requires reconstitution prior to being
`administered to a patient.
`
`2
`
`Sandoz Exhibit 1009 Page 2
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`

`

`Appl. No. ll/788,076
`Declaration Under 37 C.f.R. §1.132 by Dr. Harry G. Brittain
`
`11 .
`
`It is my understanding that concentrated ampule formulations of nicardipine
`hydrochloride present a number of issues for patients and health care
`professionals including:
`
`The requirement of dilution can result in a lag time that prevents a patient in
`an acute setting from receiving the drug in a timely fashion. From my
`experience working in the pham1aceutical industry, l know that after an order
`is written by a physician in a hospital setting, it can sometimes take up to 2
`hours or longer for the recon~tituted product to be available to the patient.
`This results in the health care professional facing the choice of either a
`dangerous delay in administration of a potentially life-saving therapeutic
`agent, or replacing the preferred fonnulation with a less effective therapy that
`would be available in a more timely fashion.
`The breaking of the ampule neck may result in exposing the patient to glass
`contamination of the product and exposing health care professionals to an
`increased risk of injuring themselves when handling and breaking the glass
`ampules.
`There is an increased probability of dosing errors by requiring health care
`professionals to dilute the product. Such errors may manifest themselves as
`an overdose or an underdose if the product is not diluted properly. Likewise,
`there is an additional possibility that the concentrated form will be
`administered uas is" which is contraindicated and can result in adverse events.
`The diluted form must be discarded in 24 hours due to stability issues.
`The selection of an inappropriate diluent can have an adverse effect on the
`stability and could cause breakdown of the drug.
`
`12.
`
`The development of a storage stable, ready-to-use nicardipine hydrochloride
`intravenous product which the present invention provides addressed the issues
`presented above with respect to concentrated ampule formulations and in my
`technical opinion, has given the target patient population and the health care
`professionals serving them solutions for them all.
`
`Tbcre Was No Expedation Of Success ln Formulating A Stable Form Of A Low
`Concentration Drug
`
`13.
`
`14.
`
`Independent claim 40 recites a nicardipine hydrochloride range of about 0.1 to
`about 0.4 mglmL, and independent claims 44-46 recite a nicardipine
`hydrochloride range of about 0.1 to about 0.2 mg/mL.
`
`ln my opinion, a skilled formulator would not have expected that the non(cid:173)
`concentrated nicardipine hydrochloride composition detined by the present
`claims would be stable for long storage time periods. This opinion derives
`from my consideration of two separate and distinct issues:
`
`3
`
`Sandoz Exhibit 1009 Page 3
`
`

`

`Appl. No. 111788,076
`Declaration Under 37 C.F.R. § 1.132 by Or. Harry G. Brittain
`
`(i) The low concentration ofnicardipine hydrochloride results in a higher
`solvent-to-drug ratio as compared to a concentrated nicardipinc
`hydrochloride formulation. Since nicardipine hydrochloride is subject to
`hydrolysis and is known to degrade in the presence of water, one skilled in
`the art would have expected that the increased solvent-to-drug ratio in the
`ready-to-use low concentration fonnulation would cause increased
`degradation of the drug substance, especially if the formulation had been
`stored for an extended period oftimc. The phenomenon that lower
`concentrations of nicardipine hydrochloride are susceptible to increased
`degradation during storage is demonstrated in Figures 4A and 4B of U.S.
`Patent Application Serial No. 2007/0249689 (to Duncan et at). As shown
`in Figures 4A and 4B, the "% Total Impurities" is consistently higher for
`formulations of 0.1 mglmL as compared to 0.2 mglmL. These Figures are
`attached as Exhibit B for the Examiner's convenience.
`
`(ii) The low concentration ofnicardipine hydrochloride results in a higher
`bag surface-to-drug ratio when compared to the surface-to-drug ratio of a
`concentrated formulation in a glass ampule. On the basis ofthis surface
`area consideration, one skilled in the art would have expected an increased
`degree of nicardipine hydrochloride degradation during storage due to
`interaction of the nicardipine hydrochloride with the bag material. Tne
`phenomena that lower concentrations ofnicardipine hydrochloride are
`susceptible to increased degradation as a resul.t of bag interaction during
`storage is demonstrated in Figures SA and SB of U.S. Patent Application
`Serial No. 2007/0249689 (to Duncan et al). As shown in Figure 5A, the
`"%Drug Remaining" after 12 weeks of storage in a polyvinyl chloride
`(PVC) container (lntravia®) resulted in a nicardipine hydrochloride net
`decrease of over 15%. PVC is the material described in the McFarlane
`reference for storage of the reconstituted nieardipine hydrochloride
`concentrate. ln contrast, as shown in Figure SB of U.S. Patent Application
`Serial No. 2007/0249689, when low concentration nicardipine
`hydrochloride is stored in a non-polar bag (e.g., Galaxy®) there is
`surprisingly minimal degradation even after 25 weeks storage. These
`Figures are attached as Exhibit C for the Examiner's convenience.
`
`15.
`
`The degradation of drug is an especially important issue with the low
`concentration nicardipine hydrochloride compositions according to the present
`claims, as compared to the concentrated dosage fonns of the prior art. This is
`due to the concern that the degradation of any amount of drug in a non(cid:173)
`concentrated form will represent a greater percent of the overall drug content
`as compared to concentrated forms, and this aspect can severely limit the
`useful life for the low-dose formulation.
`
`16.
`
`It is my understanding that claim 40 has been rejected over the McFarlane
`reference in view of Solutions to Health Care Waste: Life Cycle Thinking and
`
`4
`
`Sandoz Exhibit 1009 Page 4
`
`

`

`Appl. No. 1 L/788,076
`Declaration Under 37 C.P.R. §1.132 by Dr. Harry G. Brittain
`
`17.
`
`18.
`
`19.
`
`Green Purchasing (''the Kaiser reference"). I do not think this conclusion is
`technically sound.
`
`The McFarlane reference does not describe a ready-to-use, low concentration
`nicardipine hydrochloride formulation as required by the present claims.
`Further. the McFarlane reference does not teach or suggest formulating and
`storing a readywlo-usc nicardipine hydrochloride formulation such that the
`solution does not come into contact with polar polymers as recited in
`independent claim 40, or wherein the conUlincr is a copolyester, polyethylene,
`or polyolcfin as recited in dependent claim 43 and independent claims 44-46.
`
`The Kaiser reference is directed to health care waste and thus addresses a
`different problem (i.e., the incineration of plastic bags) than that which is
`solved by the present invention. The Kaiser reference provides no guidance
`on stability issues with a low concentration, solution-phase, fonnulation of a
`drug substance that is subject to hydrolysis, such as nicardipine hydrochloride.
`One skilled in the fom1ulation arts would have no reason whatsoever to look
`to the Kaiser reference for guidance on fonnulating a stable low
`concentration, ready-to-use, nicardipine hydrochloride composition.
`
`The only product described in the Kaiser reference as being stored in
`polyolefin containers is platelets. The Kaiser reference described that there
`was "no consistent differences" between PVC and polyolefin. This
`observation provides further evidence that one of skill in the art would have
`had no expectation of success in preparing a stable, ready-to-use, low
`concentration formulation of the present invention. This unexpected success
`is evident in Figure 5B of U.S. Patent Application Serial No. 2007/0249689
`which does show a "consistent difference" when comparing drug stability in
`polyolefin and PVC containers.
`
`The Prior Art Teaches Away From Certain Embodiments Of The Invention
`
`20.
`
`21.
`
`Claim 42 includes the limitation that the phannaceutical composition
`comprises sorbitol at from about l mglmL to about 4 mg/mL, and claims 45-
`46 include the limitation that the phannaceutical composition comprises
`sorbitol at from 0 mg/mL to about 4 rng/mL.
`
`It is my understanding that claim 42 is being rejected over the McFarlane
`reference in view of the Kaiser reference, and further in view of the Ogawa
`reference. The Examiner has conceded that the combination of McFarlane
`and Kaiser does not teach the sorbitol levels as presently claimed and the
`Ollice Action relies on Ogawa for describing preparations with sorbitol at
`these levels.
`
`5
`
`Sandoz Exhibit 1009 Page 5
`
`

`

`Appl. No. 111788,076
`Declaration Under 37 C.F.R. § 1. I 32 by Dr. Harry G. Brittain
`
`22.
`
`23.
`
`In my technical opinion, the Ogawa reference teaches away from including
`sorbitol in a nicardipine hydrochloride in the presently claimed amounts.
`
`The Ogawa reference describes nicardipine formulations that must include a
`polyhydric alcohol (e.g., sorbitol) in an amount of2·7 w/v %. for example, at
`column 1, lines 46-51, the Ogawa reference states that:
`
`"As the result of fu:rther investigations, it has been discovered that when
`nicardipine chloride {sic] is dissolved in water together with 2 to 7 WfTIOAI
`of a po/yhydric alcohol, a stable aqueous solution of nicardipine
`hydrochloride is unexpectedly obtained and based on the discovery, the
`invention has been attained. "
`
`24.
`
`In the Ogawa reference, the unit ofw/v% is a different measurement than the
`presently claimed measurement which uses units ofmglmL. However, it is
`well known in the art that the two units are related by the simple relation:
`
`w/v % is equivalent to (glmL) times I 00
`
`25.
`
`Converting the polyhydric alcohol limitations of about 1 mg/mL to about 4
`mg/mL in claim 42 according to this calculation yields a value of about 0.1
`w/v %to about 0.4 w/v %, according to the following calculations:
`
`l mglmL = .00 I g/mL and .001 glmL * I 00 == 0.1 w/v %
`
`4 mg/mL = .004 g/mL and .004 glmL • l 00 = 0.4 w/v %
`
`26.
`
`27.
`
`As discussed above, the Ogawa reference teaches that in order to achieve
`stable aqueous solution ofnicardipine hydrochloride, 2-7 w/v% is a necessary
`component. The lower limit of the range in the Ogawa reference (2 w/v %) is
`500-2000% higher than the range in claim 42 (0.1 w/v% to 0.4 w/v %).
`Similarly, claims 45 and 46 encompass stable aqueous nicardipine
`formulations that exclude sorbitol (0%) and that have an upper limit (0.4 w/v
`%). ·rhus, the lower limit of the Ogawa reference (2 w/v %) is 500% higher
`than the upper limit of claims 45 and 46.
`
`The Office Action points to Example 7 of the Ogawa reference which
`describes a 1 mg/mL nicardipine hydrochloride composition containing 20
`mg/mL sorbitol, which corresponds to a nicardipine-to-sorbitol ratio of 1 :20.
`The Examiner states that with a range ofnicardipine ofO.I to 0.4 mglmL (as
`recited in claim 40) the ratio of 1:20 would result in 2-8 mg/mL sorbitol,
`which is within the claimed range. Thus, the Office Action states that if the
`nicnrdipine concentration is decreased in accordance with the present claims,
`the skilled artisan following the teaching of the Ogawa reference would
`linearly decrease the sorbitol to achieve the claimed range.
`
`6
`
`Sandoz Exhibit 1009 Page 6
`
`

`

`Appl. No. 111788,076
`Declaration Under 37 C.F.R. §1.132 by Dr. Harry G. Brittain
`
`28.
`
`29.
`
`30.
`
`This position by the Examiner goes against the direct teachings of Ogawa
`which require that the 2-7 w/v% concentration of sorbitol be maintained
`regardless of the concentration ofnicardipine hydrochloride provided.
`
`I rely in reaching this conclusion on the evidence provided by Example 15 of
`Ogawa. which describes a 0.4 mg/mL aqueous nicardipine hydrochloride
`formulation in an ampule (which is within the claimed r.tnge), but which
`includes S w/v %sorbitol (50 mg/mL). I further rely on the content of claim 1
`of the Ogawa reference, which claims a composition of0.04 w/v% (0.4
`mg/mL) nicardipine hydrochloride with a polyhydric alcohol content of2-7
`w/v %. Thus, Ogawa teaches that 2-7 w/v% of sorbitol must be maintained.
`and that one skilled in the art following this clear teaching would not linearly
`decrease the sorbitol as the amount of nicardipine hydrochloride decreases as
`the rejecticm improperly suggests.
`
`The presently claimed formulations that feature decreased concentrations or
`even no sorbitol at all therefore ltave unexpected stability in view of the
`contrary teachings of Ogawa. Example 7 of the Ogawa reference (which was
`ret~rred to by the Examiner in the Office Action) had only 47.45% drug
`substance remaining undegraded after 7 days of storage. The compositions of
`Examples 15-17 were stored for only 10 hours and therefore do not shed any
`light on the storage stability issue. Furthermore, even though the
`compositions of Examples l-14 maintained undegraded drug substance in
`amounts greater than 90% after 4 weeks (see Examples 1-4) or 1 day (see
`Examples 7-14), these same compositions had at least a 25% decrease in drug
`content by the time of the last measurement at 12 weeks (see Examples 1-4)
`and 7 days (see Examples 7-14). By contrast, compositions of the present
`invention have less than 10% decrease in the concentration of nicardipine
`hydrochloride and a total impurity formation ofless than about 3% after
`storage tor three months and even one year at room temperature.
`
`The Present Invention Meets A l.ong Felt Need In The Art
`
`31.
`
`The claims of the present application encompass the following commercial
`products which have been approved by the United States Food and Drug
`Administration in 2008 as indicated in the FDA Orange Book {Approved
`Drug Products with Therapeutic Equivalence Evaluations). The relevant page
`ftom the Electronic Orange Book is attached as Exhibit D:
`
`nicardipinc hydrochloride 20mg/200L (i.e., 0. I mglmL) in 4.8% dextrose
`nicardipine hydrochloride 40mg/200L (i.e., 0.2 mg/mL) in 5.0% dextrose
`nicardipinc hydrochloride 20mg/200L (i.e., 0.1 mg/mL) in 0.86% sodium
`chloride
`
`7
`
`Sandoz Exhibit 1009 Page 7
`
`

`

`Appl. No. 11/788,076
`Declaration Under 37 C.F.R. § 1.132 by Dr. Harry G. Brittain
`
`32.
`
`nicardipine hydrochloride 40mg/200L (i.e., 0.2 mg/mL) in 0.83% sodium
`chloride
`
`The only injectable nicardipine hydrochloride products that had received FDA
`approval prior to the introduction of the above products were concentrated
`ampule products (2.5 mg/mL) which were first approved in an NDA 16 years
`earlier (1992; see Exhibit D). In view of the issues previously discussed with
`respect to patients and health care personnel associated with concentrated
`ampule products, it is my opinion that a ready-to-usc product would have been
`the first choice for commercialization in 1992 over a concentrated ampule
`product, and that there was an unmct market need for a ready-to~use non~
`concentrated product for the entire 16 year period until the approvaJ of the
`previously described products in 2008. It is my opinion that a non(cid:173)
`concentrated ready-to-use product that solved the formulation issues
`associated with achieving a stable low concentration aqueous nicardipine
`formulation as discussed herein would have been successfully commercialized
`much sooner lhan 2008. Therefore, it is my opinion that the present invention
`meets a long-felt need, which Counsel has advised me is further evidence of
`non-obviousness.
`
`33.
`
`I hereby declare that all statements of my knowledge made herein are true,
`and thnt all statements made on information and belief are believed to be true;
`and further that these statements were made with the knowledge that willful
`false statements and the like so made are punishable by fine or imprisonment,
`or both, under Section 101 of Title 18 of the United States Code and that such
`willful false statements may jeopardize the validity of the application or any
`patent issued thereon.
`
`Respectfully submitted,
`
`~ A. £JL.· July 2, 2202
`
`Dr. Harry G. Brittain
`
`Date
`
`8
`
`Sandoz Exhibit 1009 Page 8
`
`

`

`¥ EXHIBIT A
`EXHIBIT A
`
`Sandoz
`
`Exhib 00000000000
`
`Sandoz Exhibit 1009 Page 9
`
`

`

`Harry G. Brittain, PhD, FRSC
`Center for Phannaceutical Physics
`1 0 Charles Road
`Milford, NJ 08848
`
`Email: hbrittain@centerpharmphysics.com
`
`fax: (908)-996-3560
`
`tel.: (908)-996·3509
`
`Education
`Ph.D. (Physical Chemistry)
`M.A. (Physical Chemistry)
`B.A. (Chemistry)
`
`City University ofNew York (February, 1975)
`Queens College (June, J 972)
`Queens College (June, 1970)
`
`Experience (Industrial)
`Center for Pharmaceutical Physics (Milford, NJ)
`Institute Director (May 1999 to present)
`Providing consultation in all areas of pharmaceutical physics and physical
`pharmacy, including preformulation, formulation design, and product
`characterization. Special areas of expertise are in the polymorphism of drug
`substances, and in the physical characterization of pharmaceutically related
`materials. Also consult in subjects dealing with chirality and optically active
`substances, with a special interest in enantiomeric drug substances.
`The Center for Pharmaceutical Physics features a full array of equipment
`suitable for contract work and research in solid state science and spectroscopy.
`On site is instrumentation that measures x-ray powder diffraction, differential
`scanning calorimetry, Fourier-transfonn infrared absorption spectroscopy,
`kinetic and equilibrium solubility, sutface tension, conductivity, powder
`characteristics, UVNIS absorption and diffuse reflectance, polarimetry,
`fluorescence, and circularly polarized luminescence.
`
`Discovery Laboratories, Inc. (formerly Acute Therapeutics, Inc.; Doylestown, PA)
`Vice President, Pharmaceutical Development (November 1996 to April 1999)
`Held responsibility for all non~clinical aspects of drug development at DLJ, and
`managed the entire range of analytical, pharmaceutical, and chemical
`development efforts. Also held responsibility for the design, formulation, and
`development of all new products.
`
`Ohmeda Pbarmaccutical Products I>ivision, Inc. (Murray Hill, N.J)
`Director, Pharmaceutical, Analytical, and Chemical Development (July 1994 to October
`1996)
`
`Responsible for all latter-stage aspects of drug development at Ohmeda,
`managing the Analytical, Pharmaceutical, and Chemical Development groups.
`Coordinated the CMC development of parenteral products from product concept
`to drug registration.
`
`Sandoz Exhibit 1009 Page 10
`
`

`

`Curriculum vitae, Harry G. Brittain, PhD, FRSC
`
`L>ecember, 2008
`
`Bristol-Myers Squibb Pharmaceutical Research Institute (New Brunswick, NJ)
`Senior Research Fell ow (May 1993 to J unc 1994)
`Associate Director (December 1990 to April 1993)
`Senior Group Leader (Aprill989 December 1990)
`Group Leader (November 1987 to April 1989)
`Research Fellow (November 1986 to November 1987)
`Senior Research Investigator (November 1985 to November 1986)
`Held positions entailing the supervision of groups engaged in physical analytical
`chemistry. physical pharmacy, bulk drug analysis, and dosage form analysis.
`
`Experience <Academic)
`Rutgers University (l,iscataway, NJ)
`Adjunct Associate Professor of Pharmaceutics (July 1993 to June 1997; October
`2001 to June 2002)
`Taught sections of the Advanced Pharmaceutics course, and co-sponsored
`the thesis work of one graduate student
`Lehigh University (Bethlehem, PA)
`Visiting Research Scientist (June 1998 to June 2001)
`Act as consultant to the Department of Chemistry for the design of short
`courses of interest to the pharmaceutical industry, and have taught in the
`Distance Education program
`Adjunct Associate Professor of Chemistry (Fall 1999 semester)
`Taught Chemistry-31, "Equilibria in Chemical Systems"
`
`Seton Hall University (South Orange, NJ)
`Associate Professor of Chemistry, with Tenure (September 1982 to October 1985)
`Assistant Professor of Chemistry (September 1979 to August 1982)
`Taught numerous courses in physical, general, and inorganic chemistry.
`and graduated eight Ph.D. and four M.S. students
`
`Ferrum College (Ferrum, VA)
`Assistant Professor of Chemistry (September 1976 to August 1979)
`Taught courses in general, analytical, and environmental chemistry
`
`University of Virginia (Charlottesville, VA)
`Postdoctoral Research Fellow (February 1975 to August 1976)
`Worked on chiroptical spectroscopy investigations in collaboration with
`Professors F.S. Richardson and P.N. Schatz
`
`2
`
`Sandoz Exhibit 1009 Page 11
`
`

`

`Curriculum vitae, Harry G. Brittain, PhD, FRSC
`
`December, 2008
`
`Awards
`Teacher-Scholar ofthc Camille and Henry Dreyfus Foundation, 1980-85
`lnnovation Quality/Productivity Award, sponsored by Bristol-Myers Squibb Co., 1990
`Fellow of the American Association of Pharmaceutical Scientists, 1991
`Research Achievement Award, APQ Section of the American Association of
`Pharmaceutical Scientists, 1998
`Author of the most frequently downloaded article C'Polymorphism and Solvatomorphism
`2005") that had been published in the .Journal of Pharmaceutical Sciences during 2007
`
`Editorial Rcsoonsibilities
`(a) Editorial Advisory Board Membership
`Journal of Coordination Chemistry, April I 986 to July 1994
`Analytical Profiles of Drug Substances, May 1988 to May 1991
`Pharmaceutical Research, February 1990 to June 1995
`Instrumentation Science & Technology, June 1990 to December 2001
`Journal of Pharmaceutical and Biomedical Research, January 1992 to April 1993
`Pharmaceutical Technology, January 1993 to present
`Chirality, January 1995 to December 2007
`Pharmaceutical Research, January 1998 to December 2005
`AAPS PharmSci, January 1999 to December 2007
`Journal of Pharmaceutical Sciences, .January 1999 to December 2005
`Journal of Pharmaceutical and Biomedical Research, January 1999 to December
`2002
`AAPS PharmSciTech, August 2001 to present
`Encyclopedia of Pharmaceutical Technology, June 2003 to present
`Drugs and the Pharmaceutical Sciences (Informa Press book series), April2005
`to present
`
`(b) Publication Management
`Journal of the Electrochemical Society, Divisional Editor, January 1984 to
`December 1987
`Analytical Profiles of Drug Substances and Excipients, Editor, June 1991 to
`December 2002
`Journal of Pharmaceurical and Biomedical Research, Assistant Editor, January
`1994 to December I 998
`American Association ofPharmaceutical Sciences Publications Board, Member
`At Large, 2001 to present
`Pharmaceutical Development and Technology, Book Review Editor, November
`1998 to present
`Profiles of Drug Substances. Excipient.<r, and Related Methodology, Editor.
`January 2003 to present
`Pharmaceutical Re.rearch. Field Editor for Preformulation, January 2003 to
`December 2005
`Journal of Pharmaceutical Sciences, Associate Editor for Physical Pharmacy,
`January 2006 to present
`
`3
`
`Sandoz Exhibit 1009 Page 12
`
`

`

`Curriculum vitae, Harry G. Brittain, PhD, FRSC
`
`December, 2008
`
`Scbolarly Activities
`Published 18 edited books since 1992
`Published over 285 research papers and book chapters since 1975
`Presented over 120 invited lectures since 1987
`Taught over 30 short-courses since 1988
`
`Compendia! <United States Pharmacopeia) Activitie.~t
`Member: USP Advisory Panel I on Physical Test Methods, formed at the
`recommendation of the Excipients Subcommittee (May 1991 to August 1995)
`Member: USP Advisory Panel II on Physical Test Methods, fonned at the
`recommendation of the Excipients 2 Subcommittee (August 1995 to April 2000)
`Member: USP Committee of Revision. Duties were divided between the Excipients 2
`Subcommittee (2/3 effort) and the Chemistry 4 Panel ( l/3 effort) (August 1995 to April
`2000)
`Chairman: tJSP EMC Expert Committee (Excipients: Monograph Content), April 2000 to
`April 2005.
`Member: USP Excipients General Chapters Expert Committee, April 2005 to present.
`
`Professional Societies
`American Association of Pham1aceutical Scientists (Fellow)
`American Chemical Society {member)
`Royal Society of Chemistry (Fellow)
`Controlled Release Sodety (member)
`Parenteral Drug Association (member)
`International Ct:ntre for Diffraction Data (member)
`Society of Fluorescence (member)
`
`4
`
`Sandoz Exhibit 1009 Page 13
`
`

`

`Curriculum vitae, Harry G. Brittain, PhD, FRSC
`
`December, 2008
`
`Books Edited by Harry G. Brittain. Ph.D.
`
`(a) Published Volumes
`
`(1)
`
`(2)
`
`(3)
`
`(4)
`
`(5)
`
`(6)
`
`(7)
`
`(8)
`
`(9)
`
`H.G. Brittain, ed.
`Analytical Profiles of Drug Substances and Excipients, volume 21
`ISBN 0-12-260821-6
`Academic Press, San Diego, 1992
`
`H.G. Brittain, ed.
`Analytical Profiles of Drug Substances and Excipients, volume ll
`ISBN 0-12-260822-4
`Academic Press, San Diego, 1993
`
`N. Purdie and H.G. Brittain, eds.
`Analytical Applications of Circular Dichroism
`ISBN 0-444-89508-6
`Elsevier Science Publishers, Amsterdam, 1994
`
`H.G. Briltain, ed.
`Analytical Profiles of Drug Substances and Excipients, volume 23
`ISBN 0-12-260823-2
`Academic Press, San Diego, 1994
`
`H.G. Brittain, ed.
`Physical Characterization of Pharmaceutical Solids
`ISBN 0-8247-9372-2
`Marcel Dekker, New York. 1995
`
`H.G. Brittain, ed.
`Analytical Profiles of Drug Substances and Ex.cipients, volume 24
`rSBN 0-12-260824-0
`Academic Press, San Diego, 1996
`
`H.G. Brittain, ed.
`Analytical Profiles of Drug Substances and Excipients, volume 25
`ISBN 0-12w260825-9
`Academic Press, San Diego, 1998
`
`H.G. Brittain, ed.
`Po(vmorphism in Pharmaceutical Solids
`ISBN 0-8247·0237-9
`Marcel Dekker, New York, 1999
`
`H.G. Brittain, ed.
`Analytical Profiles of Drug Substances and Excipients, volume 26
`ISBN 0-12-260826-7
`Academic Press, San Diego, I 999
`
`s
`
`Sandoz Exhibit 1009 Page 14
`
`

`

`Curriculum vitae, Harry G. Brittain, PhD, FRSC
`
`December, 2008
`
`(1 0) H.G. Brittain, ed.
`Analytical Profiles of Drug Substances and Excipients, volume 27
`ISBN 0-12-260827-5
`Academic Press, San Diego, 2001
`
`(11) H.G. Brittain, cd.
`Analytical Profiles of Drug Substance.~ and Excipients, volume 28
`ISBN 0-12-260828·3
`Academic Press, San Diego, 2001
`
`(12) H.G. Brittain, ed.
`Analytical Profiles ofDrug Substances and Excipients, volume 29
`ISBN 0-12-260829-1
`Academic Press, San Diego, 2002
`
`( 13) H.G. Brittain, ed.
`Profiles ofDrugSubstallces, Excipient.<:, and Related Methodology, volume 30
`ISBN 0-12-260830·5
`Elsevier Academic Press. Amsterdam, 2003
`
`(14) H.G. Brittain, ed.
`Profiles ofDrug Substances, Excipients, and Related Methodology, volume 31
`ISBN 0-12-260831-3
`Elsevier Academic Press, Amsterdam, 2004
`
`(15) H.G. Brittain, cd.
`Profiles of Drug Substances, Excipients. and Related Methodology, volume 32
`ISBN 0-12-260832-1
`Elsevier Academic Press. Amsterdam, 2005
`
`(16) H.G. Brittain
`Spectroscopy of Pharmaceutical Solids
`ISBN l-57444w893-S
`Taylor & Francis, New York, 2006
`
`( 17) M .C. Adeyeye and H. G. Brittain, eds.
`Preformu/ation in Solid Doi>age Fot:m Development
`ISBN 0·8247-5809-9
`Jnfonna Healthcarc Press
`
`(18) H.G. Brittain, ed.
`Profiles of Drug Substances, Exci'pienls, and Related Methodology, volume 33
`ISBN 0-12-260833-9
`Elsevier Academic P1·ess, Amsterdam, 2007
`
`6
`
`Sandoz Exhibit 1009 Page 15
`
`

`

`Curriculum vitae, Harry C. Drittain, PhD, FRSC
`
`December, 2008
`
`(b) Book Projects Currently in Press
`
`(19)
`
`(20)
`
`H.G. Brittain, ed.
`Profiles of Drug Substances, Excipients, and Related Methodology, volume 34
`To be published by Elsevier Academic Press
`
`H.G. Brittain, ed.
`Polymorphism in Pharmaceutical Solids, 2nd edition
`To be published by lnforma Healthcare Press
`
`(c) Book Projects under Development
`
`(21) H. G. Brittain, ed.
`Profiles of Drug Substance.~. E:xcipienls, and Re/aJed Methodology, volume 35
`To be published by Elsevier Academic Press
`
`7
`
`Sandoz Exhibit 1009 Page 16
`
`

`

`Curriculum vitae, Harry G. Brittain, PhD, FRSC
`
`December, 2008
`
`Patents of H.G. Brittain, PhD, FRSC
`
`A.
`
`1.
`
`2.
`
`3.
`
`B.
`
`1.
`
`2.
`
`3.
`
`Issued Patents
`
`B.L. Hauenstein, R. Picerno, H.G. Brittain, and J.R. Nestor, "Luminescent Oxygen
`Sensor Based on a Lanthanide Complex", United States Patent 4,861 ,727, issued August
`29, 1989.
`
`B.L. Hauenstein, R. Piccmo, H.G. Brittain, and J.R. Nestor, "Luminescent Oxygen
`Sensor Based on a Lanthanide Complex", United States Patent 5,190,729, issued March
`2, 1993.
`
`H.G. Brittain, D.A. Dickason, J. Hotz, S.L. Lyons, J.M. Ramstack, S.G. Wright,
`"Polymorphic Forms ofNaltrexone'', United States Patent 7,279,579, issued October 9,
`2007.
`
`Filed l~atent Applications
`
`H.G. Brittain, D.A. Dickason, J. Hotz, S.L. Lyons, J.M. Ramstack, S.G. Wright,
`"Polymorphic Forms ofNaltrexone"