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`DECLARATION OF DUNCAN HALL
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`
`1. I am a Records Request Processor at the Internet Archive, located in San Francisco,
`California. I make this declaration of my own personal knowledge.
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`2. The Internet Archive is a website that provides access to a digital library of Internet
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`3. The Internet Archive has created a service known as the Wayback Machine. The
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`5. The Internet Archive assigns a URL on its site to the archived files in the format
`http://web.archive.org/web/[Year in yyyy][Month in mm][Day in dd][Time code in
`hh:mm:ss]/[Archived URL] aka an “extended URL”. Thus, the extended URL
`http://web.archive.org/web/19970126045828/http://www.archive.org/ would be the
`URL for the record of the Internet Archive home page HTML file
`(http://www.archive.org/) archived on January 26, 1997 at 4:58 a.m. and 28
`seconds (1997/01/26 at 04:58:28). The date indicated by an extended URL applies
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`6. Attached hereto as Exhibit A are true and accurate copies of screenshots of the
`Internet Archive's records of the archived files for the URLs and the dates specified
`in the attached coversheet of each printout.
`
`Miltenyi Ex. 1006 Page 1
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`7.
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`I declare under penalty of perjury that the foregoing is true and correct.
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`Miltenyi Ex. 1006 Page 2
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`EXHIBIT A
`EXHIBIT A
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`Miltenyi Ex. 1006 Page 3
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`Miltenyi Ex. 1006 Page 3
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`

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`https://web.archive.org/web/20090507184629/https:/clinicaltrials.gov/ct2/show/NCT0089121
`5
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`Miltenyi Ex. 1006 Page 4
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`I ~I; l i: 11' L l
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`\ H r ; 1 I /J [
`
`lhtrps:/ /d infcaltrials.gov/ct2/show/NCT00891.2 l S
`
`5 carirures
`~ ,.,v O.O!i - '\!Jun ."!02~ ,
`
`Clinica/Trit,ls.gov
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`As ervice of the U.S. t~~ion•I Institutes of Heillth
`
`Full Text View
`
`II
`
`II
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`SE:P
`►
`2011
`
`E:l
`
`0
`
`fJ
`
`Pilot Study for Patients With Chemotherapy Resistant or Refractory CD19 Leukemia and Lymphoma (CART-19)
`
`This study Is not yet open for participant recruitment.
`Ven1ied by Univers~y of Pennsylvan1a, April 2009
`
`First Rereived : April 29, 2009
`
`last Updated: Apr1l 30, 2009 Hislo[¥ of Changl!§.
`
`Sponsors and Collab0ra1or.,1: University of Pennsylvania
`Lenligen Corporation
`
`lnformaUon provided by:
`
`lJniverslty of Pennsylvania
`
`Cllnlcalnlals.gov ldenUHer: NCT00891215
`
`► Purpose
`
`This is a study for people who have been previously lreated For Leukemia/Lymphoma. In particular, it is a study for peop'le who have a type of Leukemia/lymphoma that involves B cells (a
`type o1 while rell), which contain the cancer. This is a new approach tor treatment of Leukemia/Lymphoma that involves B cells (tumor cells) , This study wi ll take the subject's while blood
`cells (T cells) and modify them in order lo largel the cancer.
`
`The subjecl's T cells will be modified in one or two different ways lhat will aJlow the cells to idenlify· and kil l the tumor cells (B cells), Both ways ol modifying lhe cells tells the T cells to go lo
`the B cells (tumor cells) ahd turn "on" and potentially kill lhe B cells (tumor cells) . The modification is a genetic change to !he T cells. or gene transfer, In order to allow the modified T cells lo
`recognize your tumor cells but not other normal cel ls in the subjecrs body, These modified cells are called CAAT-19 T cells ,
`
`The two lypes ol CAAT-19 T cells will be given back lo subject's through an inluston, In addition to determin,ng the safety of this approach, the purpose of the study is to determine which
`way 01 modlfylng the T cells works better In turning them · on• to tight cancer, This Is done by monllonng levels or bo1J1 types or modllled cells In tne subject's blood stream, and II poss101e, In
`the bone marrow and tumor tissue for four weeks alter the infusion. It is expected that one type of modified cell wil l grow better than the other in the subject's blood . However, it is possible
`that there will be no difference between t he two types of• cells.
`
`Condition
`
`Acute Lymphocytic Leukemia
`Foilicu1ar Lymphoma
`Chronic Lymphocytic Leukemia (CLL)
`Mantle Cell Lymphoma
`Prolymphocytic Leukemia
`Large Cell Lymphoma
`
`Intervention
`
`Biological : CAAT-19
`
`Phase
`
`Phase I
`
`MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chron ic 1Y.!!!P.homa
`
`U.S. '°DA Resources
`
`lntervenlional
`Study Type:
`Study Design: Treatment, Open label, Single Group Assignment, Satety/Efficacy Study
`
`Otftc1al Trtle:
`
`Pilot'Sludy ot Redirected Autologous t Cells Engineered to Contai n Anli-cdt 9 Attached to tcr~ and 4-1 bb Signaling Domains in Patients With Chemotherapy Resistanl or
`Refractory cd19+ Leukemia and Lymphoma
`
`Fu rther study detalls as provided by University of Pennsylvania:
`
`Primary Outcome Measures:
`The change in the ratio of lhe vector transduced cells to each other between baseline and week four will be evaluated. Observation and monitoring ol patients will
`continue on a monthly basis until week 24 post dosing. I Time Frame : 24 Weeks l I Designated as safely issue: Yes l
`
`Secondary Outcome Measures:
`• Subjects 6 to 10 will be dosed with mixlures ol 1CR :4-1BB and TCA or1ly cells, using a compelilive repopulalion strategy to determine the optimal sjgnal transduction
`module in the chimeric receplor" I Time Frame : 24 Weeks ] f Designated as safety issue: No J
`
`Estimated Enrollment:
`Study Start Date:
`Estimated Study Completion Date:
`Estimated Primary Completion Date:
`
`10
`June2009
`June 2010
`June 2010 (Final data collection date lor primruy outcome measure)
`
`Intervention Oelails:
`
`Biologicat: CART-19
`TotaJ dose of CAAT-19 T Cells ; -2xE9 - 5xE10. CAA'T-19 Cell lnlusion given over.a days (Day 1, Day 2 , Day 11) Each intusion is approximately 20 minures.
`Detailed Description:
`
`This is an open label, single center, pilot study to evaluate the safely and tolerability, and differential persistence and engraltment of autologous T cells engineered to express
`a chimeric anl.igen receptor targeting CD19 which is linked either to the CD3 or CD3 :4-1 BB signaling chains in a competttive repopulation setting In patients wtth
`chemotherapy-resistant or - refractory CD19+ leukemia or lymphoma, Upon enrollment, patients will undergo leukapheresis (10L) and an optional bone marrow+/- lymph
`node biopsy approximately four weeks prior to dosing. T cells will be isolated from the leukapheresis by elutriation, split and genetically modified in parallel by a lentMral vector
`expressing one of the two chimeric antigen receptors, and then the cells will be expanded in parallel. Between dosing and treatment, patients may undergo an additional
`chemotherapy treatment depending upon their di.seese. Al dosing, patients will receive a mixture of the redirected autologousT cells .against CD19 (CAAT-19 cell s), Which
`were produced in parallel. Twenty minutes afte< dosing, blood samples will be taken to serve as a baseline control for the ratio betweer> the cells with either vector. Patients will
`be monitored weekly for four weeks. At the end ol lour weeks, patients will undergo a second leukapheresis (2L) and second optional bone marrow+/- lymph node biopsy. At
`this point the patient will aJso undergo restaging. The change in the ratio of the vector transduced cells to each other between baseline and week four will be evaluated.
`Observation and monitoring of patients Will continue on a monthly basis until week 24 post dosing. AnnuaJ follow-up Jar lentiviral vector safety wil l be carried out for 15 years in
`accordance with FDA guidelines for retrovlral vectors. Ten subjects will be targeted for this study, with an expected rate of drop out of 30¾ due to disease progression between
`·enrollment and week four post dosing.
`
`Miltenyi Ex. 1006 Page 5
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`► Eligibility
`
`Ages Eli.gible for Study:
`Genders Eligible for Study:
`Accepts Healthy Volunteers:
`
`18; Years to 90 Years
`Both
`No
`
`Criteria
`
`Inclusion Criteria:
`CD19+ ACUTE'LYMPHOBLAStlC LEUKEMIA (ALL), Must be ,n CR2 or CR3 and not.eligible for allogenetc Stem Cell Transplant because of (age1 comorbld disease, lack
`of related or unrelated donor)
`CD1'9+ FOLLICULAR LYMPHOMA. Must have at least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody (Ritu~an) therapy. Must
`have Stage Jll-lV disease. less than 1 year between last chemotherapy and most current diagnosis of pro9ressi on. Disease respondin,g or s1able after most recenl therapy
`C019-;- CHRONIC L Y.MPHOCYTIC LEUKEMIA (CLL). Musi have at' ,least 2 prior combination chemotherapy regimens (not inclllding single agent monoclonal antibody
`(Rituxan) therap,y.less than 1 year between last chemotherapy and most current diagnosis of progression. Disease responding or stable after most recent therapy. Nol
`eljgibll> or appropriate for conventional allogeneic Siem Cell Transplant.
`CD10+ MANTLE CELL LYMPHOMA. Beyond 1 sl CR with relapsed err persistent disease. Not eligible or appropriate for conventional allogeneic or autolagous SCT. Disease
`responding or stable af\er most recent therapy, Relapse alter prior autologous Sterr, Cell Transplant.
`CD19+ 8-CELL PROLYMPHOCYilC L.EUKEMIA (PlL), Relapsed or residual disease after at least 1 prlor therapy and not ellgible for allogeneic Stem Cell Transplant.
`CD19+ DIFl"USE LARGE-CELL LYMPHOMA. Residual disease after primary therapy. Not el(glble for autologous Stem Cell Transplant. Relapsed atter prior autoklgous
`Siem ·Cell Transplant. Beyond 1st CR wilh relapsed or persistent disease. Not eligible or appropriate for conventional ct autologous Siem Cell Transplant.
`Age greater or equal lo 18 years al age.
`Expected 'Survival> 12 weeks,
`Creafinine < 2.5 mg/di.
`ALT/AST< 3x normal,
`Bilorubin < 2.0 mg/di.
`Any subject who relapses alter prior aUlologous Stem Cell Transplant Will be eligible regardless of other pfiof therapy.
`Adequate venous access for apheresis and, no other reasons that subj'ect cannot undergo apheresis.
`Able lo give voluntaly informed consent.
`
`Exclusion Criteria;
`
`Women who are pregnant or lactating.
`Subject has uncontrolled active infection,
`Subject has HIV
`Subject has active Mepafitis 9 or Hepafitl~ C i·nfeclion.
`Subject uses .systemic steroids (lnhaled steroids are ok).
`Subject has previously been given any gene therapy products.
`Subject has any uncontrolled active medfcal disorder that would preclude partlcipation in th1s study.
`
`► Contacts and Locations
`
`Please refer to this study by its Clln1caJTrials.gov ide~tifler: NCT00891215
`
`Contacts
`
`Contact: David Porter, MD
`
`!rnctu@mrul.med.uf1enn.edu
`
`Locations
`
`United States, Pennsylvania
`
`University of Pennsylvania
`Philadelphia, Pennsylvania. Unttecl Stales, 19104
`
`Sponsors ancl Collaborators
`University of Pennsyl'vanla
`lentigen Corporation
`
`Investigators
`
`Principal lnvestigatorc Davi'd Porter, MO University of Pennsylvanfa
`
`► More Information
`
`Additional Information:
`
`Abramson Cancer Center Clinioal Trials ~
`
`No publications provided
`
`Responsible Party:
`
`Study ID Numbers:
`Study Ar.st Received:
`Last Updated:
`ClinicalTrials.gov Identifier:
`Health Authority:
`
`Unrversity of Pennsylvania ( Dr, Carl H. June, Director, ir<V1slatfonal Reseaicn Programs, Abr<IJl1son Cancer Cen.ter, Professor of Patt,oJogy and Laboratory
`Medicine)
`UPCC 04409
`April 29, 2009
`April 30, 2009
`NCT00891215 Hlslo[Y. of Chang!!§.
`United Slates: Food and Drug AdministraOon
`
`Keywords provided by University ol Pennsylvania,
`CD19.f
`Leukemia
`lymphoma
`
`Study placed in ihe following topic categories:
`Leukemia, lymphoid
`lymphoma, Large B-Cell, Diffuse
`Protymphocytic Leuk.emia
`Precursor Cell Lymphoblaslic leukemi a-l ymphoma
`tmmur,oproliferaU\le Disorders
`Lymphoma, Mantle-Cell
`Lymphoma, Follicufar
`••~ ... ti.-. r-.... 11 I ., ....... i...,.._.,..
`
`Chronic Lymphocytlc l eukemia
`l eukemia, Prolym,phocytic
`8-<:ell lymphomas
`leukemia, lymphocytio, Chronic, 8-Cell
`lymphoma, Large-cell
`Leukemia, 8-cell, Chronic
`lymphoma, Non-Hodgkin
`1.,.,.1,,......,.il"I D r-... u
`
`Miltenyi Ex. 1006 Page 6
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`nna.1 " 1c vc11 1-y11,...,1rv11 1a
`
`Follicular lymphoma
`lymphoma, B--Cell
`Leukemia
`lymphatic Diseases
`
`Additional relevant MeSH terms:
`Leukemia, Lymphoid
`l ymphoma, l arge B-Cell. Diffuse
`lmmunoproliferative Disorders
`Precursor Cell l ymphoblastic Leukemia-Lymphoma
`Neoplasms by Histologic i ype
`Immune System Diseases
`lymphoma, Mantle-Cell
`Lymphoma, Follicular
`Lymphoma, B-Cell
`
`ClinicalTrials.gov processed this record on May 07, 2009
`
`1..lt::Uf\ic;"ll , I Q. u-vc11
`
`Lymphoprollferative Disorders
`lymphoma
`Acute lymphoblastic Leukemia
`
`lymphatic Diseases
`Leukemia
`Neoplasms
`Leukemia, Prolymphocytic
`Leukemia, Lymphocytic, Chronic1 B-Cell
`Lymphoma, Non-Hodgkin
`Leukemia, B-Cel l
`Lymphoproliferative Disorders
`Lymphoma
`
`IJ,S. Nauona! uorarv 01 M&dla'lo contact tt9lP- DOS'K.
`U.S. Nallon;:it tnstllUTes 01 Haal1h U.S. OtlQ"Brtmant or lioaltn a human Sorvl.!:"os-.
`.t.JsA.q!W ~~9!!!- Prrvac:~ Acct1~bu1~. R OOi:f{lm o.1 lntmmatlan Act
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`Miltenyi Ex. 1006 Page 7
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