Filed on behalf of: CSL Behring GmbH and CSL Behring LLC
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`
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`CSL BEHRING GMBH and CSL BEHRING LLC,
`Petitioners,
`
`v.
`
`
`
`SHIRE VIROPHARMA INC.,
`Patent Owner.
`
`__________________
`
`
`
`U.S. Patent No. 9,616,111
`
`__________________
`
`
`
`DECLARATION OF THOMAS MACHNIG & HANNO WALDHAUSER
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`Page 1 of 25
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`CSL EXHIBIT 1013
`CSL v. Shire
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`

`

`DECLARATION
`
`We. Thomas Mach'nlg‘. MD. and Hanno Waldhauser, declare:
`
`1.
`
`We are both permanent and full-time employees of CSL Behring.
`
`a.
`
`I. Thomas Machnig, am a trained physician for internal medicine and
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`hold the position of Director Medical Affairs at CSL Behring since Sept.
`
`2010.
`
`.
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`l, Hanno Waidhauser, am a trained commercial clerk and marketing /
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`communication specialist and hold currently the position of Director
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`Marketing at CSL Behring and was acting as Senior Global Product
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`Manager in March 2012 at time of the 2012 AAAAI Annual Meeting
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`(March 2-6r 2012).
`
`in Subjects with
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`Pharmacodynamics (PD) of Subcutaneous (SC) CINRYZE® (C1 Esterase Inhibitor
`
`2.
`
`We both attended the 2012 American Academy of Allergy, Asthma &
`
`immunology (AAAAI) annual meeting that was held from March 2 to March 6 in Orlando,
`
`Florida. The meeting was attended by nearly 5.000 delegates from over 60 countries
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`and featured 960 abstracts, 370 educational sessions, and 144 exhibitors. See meeting
`
`summary
`
`provided
`
`at
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`http://enews.aaaai.org/april—2012/news-briefs/thousands-
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`assemble—in-orlandmfbr—theZO12—annual-meeting. Attendees included an international
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`audience of primarily physicians and specialists in the area of allergy and immunology,
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`as well as academics and industry representatives of companies who operate in the
`
`same field, most of them having exhibitor booths during the conference.
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`3.
`
`The attached Exhibit A is a true and accurate reproduction (scanned copy)
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`of a hardcopy handout of a poster
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`titled "Safety, Pharmacokinetics
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`(PK), and
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`[Human]) with Recombinant Human Hyaluronidase (rHuPHZO)
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`Page 2 of 25
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`
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`Hereditary Angioedema (HAE)" by J. Schranz et al. that was displayed during the 2012
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`AAAAI annual meeting (“Schranz poster”). The METHODS section of the poster
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`(enlarged as Exhibit 3) includes “Figure 1. Study Design," which provides a simple
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`graphical representation of a “Prior 200 Study" and a “Current 204 Study.” TheFigure
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`discloses that CINRYZE" was subcutaneously administered to participants in the “Prior
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`200 Study" at concentrations of 333.3U/mL (1 .OOOU in 2 separate injections of 1.5mL or
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`2.000U in 4 separate injections of 1.5mL).
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`4.
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`The Schranz poster was displayed as a late breaker abstract on Tuesday,
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`March 6th. at 9:45AM ET) in the poster viewing area / hall close to the industry
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`exhibition area of the conference and accessible to all
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`registered delegates and
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`exhibitors of the conference. As discussed in paragraph 2. there were approximately
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`5,000 people in attendance at the conference, all of whom were permitted to view the
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`poster.
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`In our recollection. the poster was presented by one of the authors on-site (as
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`mandated by the conference) and discussed with relevant physicians who are actively
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`treating patients with Hereditary Angioedema as well as other industry representatives
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`of other manufacturers of HAE therapies (including CSL Behring) while it was on
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`display.
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`5.
`
`Presenting authors as well as representatives of ViroPharma (at that time
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`ViroPharma was sponsoring the research of the study which results we're presented in
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`the Schranz poster) were present on-site i.e. near the poster and provided answers to
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`viewers. Handouts of the poster were freely available and picked-up by us as well as by
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`Page 3 of 25
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`Page 3 of 25
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`'-
`‘
`~
`--7
`-
`-
`r - ~ v v-
`r
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`l
`
`other poster viewers.1 The abstract of the poster was published as L21 in the abstracts
`
`section of the Joumal of Allergy and Clinical Immunology. Vol.129, issue 2', A3369, Feb.
`
`2012 (see attached Exhibit C).
`
`in addition, ViroPharma and Halozyme issued a press
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`release through the PR Newswire service on March 6. 2012 titled "ViroPharma and
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`Halozyme Announce Positive Data of Subcutaneous Cinryze® (C1 esterase inhibitor
`
`[human]) with Recombinant Human HyalUronidase (rHuPH20)" (see attached Exhibit D)
`
`confirming the presentation of
`
`a‘ poster by Jennifer Schranz entitled “Safety,
`
`Phrmacokineti‘cs (PK), and Pharmacodynamics (PD) of Subctuaneous (SC) Cinryze®
`
`(C1 inhibitor ('01 INH) with Recombinant Human Hyaluronidase (rHuPH20) in Subjects
`
`with Hereditary Angioede'ma (HAE) at the 2012 annual AAAAI meeting held March 2-6
`
`in Orlando, Florida. Finally, a Biotechnology — Company Report of ViroPharma
`
`Incorporated by JMP Securities (attached as Exhibit E) mentions on the day thereafter
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`that the presentatiOn of the Schranz poster took place at the 2012 AAAAI Annual
`
`Meeting, and discloses a summary of the poster together with a Figure of the mean
`
`plasma C1-INH FUnctional Concentration (Figure 2 of the Schranz poster).
`
`We further declare that all statements made herein of our own knowledge are
`
`true and that all statements made on information and belief are believed to be true.
`
`i
`
`l
`
`1 While we do not know how many copies of the Schranz poster were taken by viewers
`during the meeting, we note that we have typically distributed between 50-100 copies of
`the posters we have presented at similar conferences.
`
`3
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`Page 4 of 25
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`Page 5 of 25
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`Page 5 of 25
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`Exhibit A
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`Exhibit A
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`Page 6 of 25
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`Page 6 of 25
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`Page 7 of 25
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`Page 7 of 25
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`Exhibit B
`
`Exhibit B
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`
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`
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`‘All doseswere elven Mloeweeklvfor 2weeks
`
`
`
`METHODS CONT’D
`
`0 Subjects in Study204Ieoeiveda total 014 doeeeofClNHYZE with rHuPH20 (on Days 1.4.8.11)
`during the study period
`
`- Safetv was assessed bv monitoring advetse events (AE3). finances in vital sinus. and laboratorv testino
`
`- Ptesenoeofc1 INH antibodieswasaeseesedon Day18end30dayeafiertheiestdeeeofstudydmg
`
`0 Phennecokinefic parameters:
`
`0 Plasma 01 INH functional activity was assessed by ohmmogenic assay and plasma C1 INH antigenic
`concentration andO4complemeMlevelswereaasessedbyaJSA
`
`o Noneompartmantal model analysis (Winth 5.3) was performed on the concentmfiondversus-
`time data
`
`0 Parameters of intemst area under the curve at steady state much"; exposure at steady state
`considered betweaa 0-96 ht), Om, average concentration at steady state [Cavg]. and relative
`bioavaitabiiity (F)
`
`
`
`
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`Page 8 of 25
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`Page 8 of 25
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`Exhibit C
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`Exhibit C
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`Page 9 of 25
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`Page 9 of 25
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`

`

`THE JOURNAL OF
`AllergymClinical
`Immunology [W4
`
`American Academy of
`
`_& Immunolog
`
`AMERICAN ACADEMY OF ALLERGY,
`ASTHMA & IMMUNOLOGY
`
`
`
`2012 AAAAI Annual Meeting
`
`Orlando, FL
`
`March 2-March 6, 2012
`
`Program and abstracts of papers to be presented
`
`during scientific sessions
`
`Abstract sessions programmed by the AAAAI
`
`J ALLERGY CLIN IMMUNOL
`
`February 2012
`
`1A
`
`Page 10 of 25
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`Page 10 of 25
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`

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`
`
`THE JOURNAL OF
`Allergym Clinical
`Immunology
`
`A6698
`
`
`
`VOLUME 129 0 NUMBER 2
`
`American Academy of
`Allergy Asthm
`
`& lmmunolog_
`
`OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF ALLERGY, ASTHMA & IMMUNOLOGY
`
`Meeting Information
`
`Abstracts
`
`Saturday, March 3
`
`Sunday, March 4
`
`Monday, March 5
`
`Tuesday, March 6
`
`Scientific Program
`
`Alphabetic Index by Abstract Authors
`
`Keyword Index
`
`Author Disclosures
`
`Late—Breaking Abstracts
`
`Author Disclosures for Late—Breaking Abstracts
`
`3A
`
`ABl
`
`AB72
`
`AB 147
`
`ABZI 1
`
`A3251
`
`AB305
`
`AB326
`
`AB33 1
`
`AB364
`
`AB372
`
`
`© 2012 American Academy of Allergy, Asthma & Immunology
`
`Statements and opinions expressed in the articles and communications herein are those of the author(s) and not necessarily those of the Editor(s), the pub—
`lisher, or the AAAAI. The Editor(s) and publisher disclaim any responsibility or liability for such material and do not guarantee, warrant, or endorse any
`product or service advertised in this publication, nor do they guarantee any claim made by the manufacturer of such product or service.
`
`2A February 2012
`
`Page 11 of25
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`J ALLERGY CLIN IMMUNOL
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`Page 11 of 25
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`
`J ALLERGY CLIN IMMUNOL
`VOLUME 129, NUMBER 2
`
`Abstracts A8369
`
`measured at different times. Also, no change was seen in skin test,
`intradermal test and specific antibodies.
`CONCLUSIONS: This preliminary study suggests that the micro-syringe
`challenge with honeybee venom is feasible, and produces results undis—
`tinguishable from those of the traditional sting challenge. An application
`also to vespid venom is under evaluation.
`
`L2 Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD)
`of Subcutaneous (SC) Cinryze® (C1 inhibitor (01 INH) with
`Recombinant Human Hyaluronidase (rHuPH20)
`in Subiects
`with Hereditary Angioedema (HAE)
`lacobss, S. S.
`J. Schranz‘, R. Levyz, W. Lumrys, M. Manning“, J.
`Dychter6, M. J. LaBarreG, A. Phillipsl, S. Gelonel, C. Brooml; lViro-
`Pharma Incorporated, Exton, PA, 2Family Allergy and Asthma Center, At-
`lanta, GA, 3AARA Research Center, Dallas, TX, 4Allergy and
`Immunology Associates, Scottsdale, AZ, 5Allergy and Asthma Clinical
`Research, Inc., Walnut Creek, CA, 6Halozyme Therapeutics, San Diego,
`CA.
`RATIONALE: HAE manifests as recurrent painful, disabling, and
`sometimes fatal swelling attacks. CINRYZE administered by the IV route
`replaces deficient and/or dysfunctional Cl INH and has proven efficacy
`and safety for both acute treatment and prevention. In order to provide
`broader options for patients to control disease, the potential enhancement
`of CINRYZE SC dispersion and absorption when co—administered with
`rHuPH20 was assessed in HAE patients.
`METHODS: This open-label, multiple-dose study was conducted in 12
`HAE patients who received twice—weekly 1000 or 2000 U SC doses of
`CINRYZE co—adrninistered as a single injection with rHuPH20 for 2
`weeks. Comparisons were made to data from the same subjects who had
`prior exposure to ClNRYZE without rHuPH20. Safety, tolerability, PK/
`PD, and irnrnunogenicity were assessed.
`RESULTS: SC CINRYZE co~adrninistered with rHuPH20 was well
`tolerated, with no AEs leading to discontinuation or SAEs. Mild/moderate
`injection site reactions were noted in the majority of subjects, with severe
`erythema reported in 2 subjects. Co—administration with rHuPH20 resulted
`in increased CINRYZE systemic exposure relative to SC administration of
`CINRYZE alone. Preliminary mean values attained were: functional C1
`INH exposure of 36—61 hr-U/mL', Cmax of 0.43—0.72 U/mL; antigenic Cl
`INH level of 0.13—0.24 glL and C4 was 174-210 mg/mL. No subjects had
`detectable C1 INH antibodies in plasma 30 days after the last dose.
`CONCLUSIONS: CINRYZE co-administered as a single SC injection
`with rHuPH20 was well tolerated and resulted in physiologically relevant
`functional Cl INH levels. Evaluation of the efficacy and safety of this
`innovative combination therapy is planned.
`
`L1
`
`Hypoallergenicity, Growth and Tolerance of an Amino Acid
`Based Formula (AAF) with Synhiotics in Allergic and Healthy
`Infants and Children
`
`B. M. Harvey‘, s. M. Gillrnanz, J. E. Langfords, T. D. Green", R. H.
`Schwartzs, A. W. Burksé; 1Children’s Investigational Research Program,
`LLC (CHIRP), Bentonville, AR, 2Children’s Hospital of Orange County,
`Orange Country, CA, 3Nutricia Advanced Medical Nutrition, Danone Re—
`search Centre for Specialised Nutrition, Liverpool, UNITED KINGDOM,
`4Children’s Hospital of Pittsburgh, Pittsburgh, PA, Slnova Fairfax Hospital
`for Children, Virginia, VA, 6Duke University Medical Center, Durham,
`NC.
`RATIONALE: Cow’s milk allergy (CMA) affects 2-5% of infants and
`children in Western countries. Study 1 evaluated the effects of an AAF
`containing synbiotics (a specific mixture of short & long chain fructo-
`oligosaccharides and pectin derived acidic oligosaccharides [0.8g/100ml]
`+ Bifidobacterium Breve M—16V [1.3x109CFU/100ml]) on overall growth
`and tolerance in healthy, term infants. In study 2 the hypoallergenicity of
`the AAF containing synbiotics was evaluated in infants and children
`with documented CMA according to AAP guidelines.
`METHODS: In study I, a total of 115 healthy, full—term formula fed
`infants (10 :4 days) randomly received the AAF with synbiotics or a
`commercially available control AAF without synbiotics (Neocate Infant
`DHA & ARA®, Nutricia Liverpool, UK) for 16 weeks as sole source of
`nutrition. Anthropometric measurements, tolerance, and adverse events
`were recorded throughout the study. In study 2, the hypoallergenicity of the
`AAF with synbiotics was evaluated in 30 infants and children (aged 0—3
`years) with IgE mediated CMA using a double—blind placebo—controlled
`food challenge (DBPCFC) and a 7 day feeding period.
`RESULTS: In study 1 overall growth as measured by weight, length and
`head circumference, tolerance and safety outcomes were similar in both
`groups at week 16. In study 2, all 30 subjects completed the DBPCFC with
`no reported allergic reactions.
`CONCLUSION: The resnlts of these studies demonstrate that an AAF
`with synbiotics is safe, well tolerated and promotes normal growth when
`fed to healthy term infants as a sole source of nutrition and is hypoaller-
`genic in CMA infants and children.
`
`L2 Bee Venom Challenge By A Micro-syringe: Validation
`Procedure
`G. Cortellini‘, M. Severinoz, E. Francescatoa, s. Turillazzi", I. Spadolinis,
`G. Passalacquasg 1Rimini Hospital — Internal medicine and Rheumatology,
`Rimini, ITALY, 2Ospedale San Giovanni di Dio — Allergy clinic, Florence,
`ITALY, 3Entornon sas, Florence, ITALY, 4University of Florence - Dipar—
`timento di Biologia Evoluzionistica, Florence, ITALY, 5Anallergo, Flor-
`ence, ITALY, 6University of Genoa - Allergy and Respiratory Diseases,
`Genova, ITALY.
`BACKGROUND: The honeybee sting challenge is considered a reliable
`diagnostic procedure, expecially for experimental purpose, but difficult to
`perform in clinical practice. Objective: we assessed the feasibility and
`reliability of a challenge test using a micro sirynge and compared to the
`standard procedure.
`METHODS: Patients enrolled on bee venom immunotherapy underwent a
`sting challenge (according to Golden 2006), and were kept under 1 honr
`observation. Large local reactions, were followed—up up to 48 hours.
`Immunological parameters were assessed one month after challenge.
`Those patients displaying systemic reactions at the sting challenge were
`excluded from the syringe challenge for ethical reasons. The syringe
`challenge was done by injecting 50 mcL of fresh unfiltered bee venom at 2
`mm depth (the length of the sting left by a bee). The same follow-up as at
`the first challenge was performed.
`RESULTS: 19 patients on bee venom immunotherapy underwent the sting
`challenge with live bees. Four of them had immediate systemic reactions
`(generalized urticaria and/or asthma), and were excluded from the second
`challenge. The13 patients with large local reaction and 2 patients with no
`reaction underwent the syringe challenge. There was no significant change,
`versus the sting challenge, in the diameters of the large local reactions,
`
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`Exhibit D
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`Exhibit D
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`Halozyme Therapeutics - ViroPharma and Halozyme Announce Positive Data of Subc... Page 1 of 7
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`N EWS RELEASES DETAILS
`
`View all News Release
`
`ViroPharma and Halozyme Announce Positive Data
`
`of Subcutaneous Cinryze® (C1 esterase inhibitor
`
`[human]) with Recombinant Human Hyaluronidase
`
`(rHuPHZO)
`
`03/06/2012
`
`- Data Presented at the 2012 Annual Meeting of the American
`
`Academy of Allergy Asthma & Immunology (AAAAi) -
`
`ORLANDO, Fla, March 6, 2012 /PRNewswire/-- ViroPharma Incorporated
`
`(NASDAQ: VPHiVi) and Halozyme Therapeutics (Nasdaq: HALO) today announced
`
`the presentation of positive data from ViroPharma's Phase 2 subcutaneous trial of
`
`Cinryze® (Ci esterase inhibitor [human]) in combination with Halozyme's
`
`EnhanzeTM technology, a proprietary drug delivery platform using Halozyme's
`recombinant human hyaluronidase enzyme (rHuPHZO), in patients with hereditary
`angioedema (HAE), a rare, debilitating and potentially fatal genetic disease. The
`
`presentation occurred as part of the late—breaker session at the 2012 annual
`
`meeting of the American Academy of Allergy Asthma & immunology (AAAAi), held
`
`March 2 to 6, 2012 in Orlando, Fla. According to the presenters, these data
`
`demonstrate that subcutaneous co—administration of Cinryze with rHuPHZO was
`
`easy to administer, well tolerated and resulted in sustained physiologically relevant
`C1 lNH functional concentrations. The presenters concluded that this innovative
`
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`combination administered subcutaneously as a single injection will be further
`
`evaluated for the prevention of HAE attacks.
`
`Cinryze is approved in the United States as intravenous (IV) administration for
`
`routine prophylaxis against angioedema attacks in adolescent and adult patients
`
`with HAE, and in Europe for routine prevention, pre—procedure prevention and
`
`acute treatment of angioedema attacks in adolescent and adult patients with HAE.
`
`in poster #5208 entitled, ‘Safety, Pharmacokinetics (PK), and Pharmacodynamics
`
`(PD) of Subcutaneous (SC) Cinryze® (Cl inhibitor (Cl
`
`lNH) with Recombinant
`
`Human Hyaluronidase (rHuPH20) in Subjects with Hereditary Angioedema (HAE),'
`
`Jennifer Schranz, l\/l.D., ViroPharma's vice president of clinical research, and
`
`colleagues discussed key study results.
`
`- Cinryze with rHuPH20 was well tolerated with no serious adverse events (SAEs),
`
`and no adverse events (AEs) led to study drug discontinuation:
`
`- No subjects experienced an HAE attack during the study;
`
`0 Mild to moderate injection site reactions were the most frequently reported
`AEs.
`
`Cinryze with rHuPH20 delivered physiologically relevant Cl INH functional
`concentrations
`
`- Cinryze 2000U with rHuPH20 resulted in mean C1 lNH functional
`
`concentrations greater than or equal to 0.4U/mL for 92 percent of the 72 hour
`
`post dosing period as compared to 73 percent for 1000U lV.
`
`- Addition of rHuPH20 to Cinryze 2000U resulted in a statistically significant
`
`increase in bioavailability of C1 lNH antigen relative to Cinryze 2000U alone;
`
`' The addition of rHuPH20 to Cinryze resulted in a dose proportional increase of
`
`C1 lNH function for Cmax, Cavg, and AUCtauover the 1000 to 2000U dose range;
`
`o No Ci
`
`lNH antibodies were detected during the 30 day post treatment follow up
`
`after the last dose of Cinryze.
`
`"Cinryze administered intravenously has been shown to be a safe and effective
`
`option in the management of HAE,” said Dr. Schranz. "But HAE is not a disease for
`
`which there is a 'one size fits all' therapy; there are still unmet medical needs for
`
`novel therapeutic options to help patients manage their disease in a manner that
`
`best suits their lives. ViroPharma is developing subcutaneous delivery of Cinryze in
`
`combination with rHuPH20 to provide patients with broader options to help
`
`control their disease. The results of this study support further clinical
`
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`development of the combination, and move us closer to potentially enabling
`prevention—minded patients living with HAE to self administer the drug
`subcutaneously with a single injection per dose.”
`
`Halozyme‘s EnhanzeTM technology, a proprietary drug delivery platform using
`recombinant human hyaluronidase enzyme (rHuPHZO) facilitates the absorption
`and dispersion of drugs or fluids that are injected under the skin. Recombinant
`HuPHZO transiently generates channels in subcutaneous tissues to increase the
`absorption and spread of injected drugs.
`
`About the Study
`This open-label, multiple—dose Phase 2 study was conducted in 12 subjects with
`HAE who previously participated in the ViroPharma trial evaluating the
`pharmacokinetics of subcutaneous injections of Cinryze when given alone relative
`to intravenous infusion. Qualified subjects participated in a single 18—day study
`period, followed by a 30—day post—treatment follow—up. A iOOOU or ZOOOU dose of
`Cinryze in combination with rHuPHZO was administered as a single subcutaneous
`injection, twice weekly, allowing within—subject comparison across the different
`methods of administration. Plasma Ci
`lNH functional activity was assessed by
`chromogenic assay and plasma Ci inhibitor antigenic concentration and C4
`complement levels were assessed by ELlSA.
`
`Additional information about this subcutaneous Cinryze clinical trial can be found
`
`at clinicaltrialsgov.
`
`About Cinwze® (Ci esterase inhibitor [human])
`Cinryze is a highly purified, pasteurized and nanofiltered plasma-derived Cl
`esterase inhibitor product.
`in the U.S., Cinryze is approved by the FDA for routine
`prophylaxis against angioedema attacks in adolescent and adult patients with
`HAE.
`in the EU, the product is approved by the EMA for the treatment and pre—
`procedure prevention of angioedema attacks in adults and adolescents with
`hereditary angioedema (HAE), and routine prevention of angioedema attacks in
`adults and adolescents with severe and recurrent attacks of hereditary
`angioedema (HAE), who are intolerant to or insufficiently protected by oral
`prevention treatments or patients who are inadequately managed with repeated
`acute treatment. Cinryze is for intravenous use only.
`
`Severe hypersensitivity reactions to Cinryze may occur. Thrombotic events have
`occurred in patients receiving Cinryze, and in patients receiving off-label high dose
`Ci inhibitor therapy. Monitor patients with known risk factors for thrombotic
`events. With any blood or plasma derived product, there may be a risk of
`transmission of infectious agents, e.g. viruses and, theoretically, the QB agent. The
`risk has been reduced by screening donors for prior exposure to certain virus
`
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`infections and by manufacturing steps to reduce the risk of viral transmission
`
`including pasteurization and nanofiltration.
`
`The most common adverse reactions in clinical trials associated with Cinryze were
`
`rash, headache, nausea, erythema, phlebitis and local reactions at the injection
`
`site. Adverse events of sinusitis and upper respiratory infection also were
`
`observed in clinical trials. No drug—related serious adverse events (SAEs) were
`
`reported in clinical trials.
`
`Please visit http://wwwviropharma.com/products/cinryze.aspx for the full U.S.
`
`Prescribing information; the prescribing information for other countries can be
`
`found at www.viropharma.com.
`
`About EnhanzeTM Technology
`
`EnhanzeTM technology is a proprietary drug delivery platform using Halozyme's
`
`first approved enzyme, recombinant human hyaluronidase or rHuPHZO. When
`
`formulated with other injectable drugs, Enhanze technology can facilitate the
`
`subcutaneous dispersion and absorption of these drugs. Molecules as large as 200
`nanometers may pass freely through the extracellular matrix, which recovers its
`
`normal density within approximately 24 hours, leading to a drug delivery platform
`
`which does not permanently alter the architecture of the skin. The principal focus
`of Halozyme‘s Enhanze technology platform is the use of rHuPHZO to facilitate
`
`subcutaneous administration for large molecule biological therapeutics, some of
`
`which currently require intravenous administration.
`
`About Hereditary Angioedema (HAE)
`
`HAE is a rare, severely debilitating, life—threatening genetic disorder caused by a
`
`deficiency of Cl inhibitor, a human plasma protein. This condition is the result ofa
`
`defect in the gene controlling the synthesis of Cl inhibitor. Cl inhibitor maintains
`
`the natural regulation of the contact, complement, and fibrinolytic systems, that
`
`when left unregulated, can initiate or perpetuate an attack by consuming the
`
`already low levels of endogenous Ci inhibitor in HAE patients. Patients with C1
`
`inhibitor deficiency experience recurrent, unpredictable, debilitating, and
`potentially life threatening attacks of inflammation affecting the larynx, abdomen,
`
`face, extremities and urogenital tract. Patients with HAE experience approximately
`20 to 100 days of incapacitation per year. There are estimated to be at least 6,500
`
`people with HAE in the United States and at least 10,000 people in the European
`Union.
`
`For more information on HAE, visit the HAEi‘s (international Patient Organization
`
`for C1 inhibitor Deficiencies) website at www.haei.org and the US. HAE
`
`Association‘s website at: www.haea.org.
`
`About ViroPharma incorporated
`
`ViroPharma incorporated is an international biopharmaceutical company
`
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`1 3.04.201 6
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`committed to developing and commercializing novel solutions for physician
`specialists to address unmet medical needs of patients living with diseases that
`have few if any clinical therapeutic options, including Ci esterase inhibitor
`deficiency, treatment of seizures in children and adolescents, adrenal insufficiency
`(Al), and C. difficile infection (CDl). Our goal is to provide rewarding careers to
`employees, to create new standards of care in the way serious diseases are
`treated, and to build international partnerships with the patients, advocates, and
`health care professionals we serve. ViroPharma's commercial products address
`diseases including hereditary angioedema (HAE), seizures in children and
`adolescents, and CDl; forfull U.S. prescribing information on our products, please
`download the package inserts at http://www.viropharma.com/Products.aspx; the
`prescribing information for other countries can be found at
`
`wvwv.viropharma.com.
`
`ViroPharma routinely posts information, including press releases, which may be
`important to investors in the investor relations and media sections of our
`company's web site, www.viropharma.com. The company encourages investors to
`consult these sections for more information on ViroPharma and our business.
`
`About Halozyme
`Halozyme Therapeutics is a biopharmaceutical company dedicated to developing
`and commercializing innovative products that advance patient care. With a
`diversified portfolio of enzymes that target the extracellular matrix, the Company‘s
`research focuses primarily on a family of human enzymes, known as
`hyaluronidases, that increase the absorption and dispersion of biologics.
`Halozyme‘s pipeline addresses therapeutic areas, such as diabetes, oncology and
`dermatology that have significant unmet medical need. The Company markets
`HYLENEX® recombinant (hyaluronidase human injection) and has partnerships
`with Roche, Baxter, ViroPharma and lntrexon. Halozyme is headquartered in San
`Diego, CA. For more information on how we are innovating, please visit our
`corporate website at www.halozyme.com.
`
`7
`ViroPharma Forward Looking Statements
`Certain statements in this press release contain forward-looking statements that
`involve a number of risks and uncertainties. Forward—looking statements provide
`our current expectations or forecasts of future events, including the therapeutic
`indication and use, safety, efficacy, tolerability and potential of Cinryze and our
`focus, goals, strategy, research and development programs, and ability to develop
`pharmaceutical products, commercialize pharmaceutical products, and execute on
`our plans including clinical development activities with Cinryze related to
`subcutaneous administration in combination with rHuPHZO. The safety,
`
`pharmacokinetics and pharmacodynamics data described in this press release are
`preliminary and additional r