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Extract from the Register of European Patents

EP About this file: EP3600345

EP3600345 - OXIDATION-RESISTANT AAT GENE THERAPY [Right-click to bookmark this link]
StatusGrant of patent is intended
Status updated on  18.02.2026
Database last updated on 28.03.2026
FormerExamination is in progress
Status updated on  27.10.2022
FormerRequest for examination was made
Status updated on  03.01.2020
FormerThe international publication has been made
Status updated on  06.10.2018
Most recent event   Tooltip28.03.2026New entry: Renewal fee paid 
Applicant(s)For all designated states
Cornell University
395 Pine Tree Road
Suite 310
Ithaca, NY 14850 / US
[2020/06]
Inventor(s)01 / CRYSTAL, Ronald G.
New York, New York 10021 / US
02 / STILES, Katie
Bronx, New York 10461 / US
03 / SOSULSKI, Meredith
New York, New York 10028 / US
04 / KAMINSKY, Stephen M.
Bronx, New York 10471 / US
05 / SONDHI, Dolan
New York, New York 10023 / US
06 / DE, Bishnu
New Hyde Park, New York 11040 / US
07 / ROSENBERG, Jonathan
Cranbury, New Jersey 08512 / US
 [2026/13]
Former [2020/06]01 / CRYSTAL, Ronald G.
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
02 / STILES, Katie
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
03 / SOSULSKI, Meredith
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
04 / KAMINSKY, Stephen M.
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
05 / SONDHI, Dolan
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
06 / DE, Bishnu
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
07 / ROSENBERG, Jonathan
32 Maplewood Avenue
Cranbury New Jersey 08512 / US
Representative(s)Forresters IP LLP
Skygarden
Erika-Mann-Straße 11
80636 München / DE
[N/P]
Former [2020/06]Gowshall, Jonathan Vallance
Forresters IP LLP
Skygarden
Erika-Mann-Strasse 11
80636 München / DE
Application number, filing date18777905.329.03.2018
[2020/06]
WO2018US25183
Priority number, dateUS201762478357P29.03.2017         Original published format: US 201762478357 P
[2020/06]
Filing languageEN
Procedural languageEN
PublicationType: A1 Application with search report
No.:WO2018183705
Date:04.10.2018
Language:EN
[2018/40]
Type: A1 Application with search report 
No.:EP3600345
Date:05.02.2020
Language:EN
The application published by WIPO in one of the EPO official languages on 04.10.2018 takes the place of the publication of the European patent application.
[2020/06]
Search report(s)International search report - published on:US04.10.2018
(Supplementary) European search report - dispatched on:EP03.12.2020
ClassificationIPC:A61K31/712, A61K48/00, C07K14/81, C12N15/00, C12N15/09, C12N15/63, C12N15/86
[2021/01]
CPC:
C07K14/8125 (EP); C12N15/86 (EP,US); A61K31/712 (EP);
A61K48/005 (EP); A61K48/00 (US); C12N2750/14141 (US);
C12N2750/14144 (EP) (-)
Former IPC [2020/06]A61K31/712, A61K48/00, C07K14/81, C12N15/00, C12N15/09, C12N15/63
Designated contracting statesAL,   AT,   BE,   BG,   CH,   CY,   CZ,   DE,   DK,   EE,   ES,   FI,   FR,   GB,   GR,   HR,   HU,   IE,   IS,   IT,   LI,   LT,   LU,   LV,   MC,   MK,   MT,   NL,   NO,   PL,   PT,   RO,   RS,   SE,   SI,   SK,   SM,   TR [2020/06]
TitleGerman:OXIDATIONSRESISTENTE AAT-GENTHERAPIE[2020/06]
English:OXIDATION-RESISTANT AAT GENE THERAPY[2020/06]
French:THÉRAPIE GÉNIQUE À AAT RÉSISTANT À L'OXYDATION[2020/06]
Entry into regional phase29.10.2019National basic fee paid 
29.10.2019Search fee paid 
29.10.2019Designation fee(s) paid 
29.10.2019Examination fee paid 
Examination procedure29.10.2019Examination requested  [2020/06]
29.06.2021Amendment by applicant (claims and/or description)
26.10.2022Despatch of a communication from the examining division (Time limit: M04)
03.03.2023Reply to a communication from the examining division
28.07.2025Despatch of a communication from the examining division (Time limit: M04)
06.11.2025Reply to a communication from the examining division
27.11.2025Despatch of a communication from the examining division (Time limit: M04)
06.01.2026Reply to a communication from the examining division
18.02.2026Communication of intention to grant the patent
Fees paidRenewal fee
21.02.2020Renewal fee patent year 03
29.03.2021Renewal fee patent year 04
28.03.2022Renewal fee patent year 05
27.03.2023Renewal fee patent year 06
27.03.2024Renewal fee patent year 07
27.03.2025Renewal fee patent year 08
27.03.2026Renewal fee patent year 09
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Documents cited:Search[Y] WO2013003641  (INHIBRX LLC et al.)
 [Y] WO9426896  (US HEALTH et al.) [Y] 1-15 * abstract * * page 4, paragraph 13 * * page 5, paragraph 13 * * page 20, paragraph 73 * * page 35, paragraph 121 *
 [Y] FR2599752  (TRANSGENE SA et al.) [Y] 1-15 * abstract * * page 3, line 35 - page 4, line 25 * * page 6, line 18 - page 7, line 16 *
 [Y]   CRYSTAL ET AL: "The alpha 1-antitrypsin gene and its deficiency states", TRENDS IN GENETICS, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 5, 1 January 1989 (1989-01-01), pages 411 - 417, XP025208042, ISSN: 0168-9525, [retrieved on 19890101], DOI: 10.1016/0168-9525(89)90200-X

DOI:   http://dx.doi.org/10.1016/0168-9525(89)90200-X
International search[XY] US4711848  (INSLEY MARGARET Y et al.) [X] 1-4 * entire document *[Y] 5, 6
 [XY] US6072029  (COURTNEY MICHAEL et al.) [X] 17-19 * entire document *[Y] 20-24
 [Y] WO2016126857  (UNIV FLORIDA et al.) [Y] 20-24 * entire document *
 [A] US9574192  (SEHGAL ALFICA et al.) [A] 1-6, 17-24 * entire document *
 [Y]   TAGGART ET AL.: "Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, no. 35, 23 June 2000 (2000-06-23), pages 27258 - 27265, XP055544656 [Y] 5, 6 * . entire document *

DOI:   http://dx.doi.org/10.1074/jbc.M004850200
 [A]   CHIUCHIO ET AL.: "Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease", ANNALS OF THE AMERICAN THORACIC SOCIETY, vol. 13, no. 4, 1 August 2016 (2016-08-01), pages S352 - S369, XP055544662 [A] 1-6, 17-24 * . entire document *

DOI:   http://dx.doi.org/10.1513/AnnalsATS.201506-344KV
 [A]   MCLEAN ET AL.: "Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency", BIOLOGICS, vol. 3, 13 July 2009 (2009-07-13), pages 63 - 75, XP055544669 [A] 1-6, 17-24 * . entire document *
Examination  JENNINGS C A ET AL: "INFLAMMATORY LUNG DISEASE MOLECULAR DETERMINANTS OF EMPHYSEMA, BRONCHITIS, AND FIBROSIS", INFLAMMATION: BASIC PRINCIPLES AND CLINICAL CORRELATES, XX, XX, 1 January 1992 (1992-01-01), pages 983 - 997, XP001149593
by applicantWO2013003641
 US5443505
 US4863457
 US5378475
   TAGGART ET AL., J. BIOL. CHEM., vol. 275, 2000, pages 27258 - 27265 [A] 1-6, 17-24 * . entire document *
   SONG SEMBURY JLAIPIS PJBERNS KLCRAWFORD JMFLOTTE TR: "Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors", GENE THER, vol. 8, 2001, pages 1299 - 1306 [A] 1-6, 17-24 * . entire document *
   WRIGHT ET AL., CURR. OPIN. DRUG DISCOV. DEVEL, vol. 6, no. 2, 2003, pages 174 - 178
   WRIGHT ET AL., MOLECULAR THERAPY, vol. 12, 2005, pages 171 - 178
   JOHNSON DTRAVIS J: "The oxidative inactivation of human alpha-1-proteinase inhibitor. Further evidence for methionine at the reactive center", J BIOL CHEM, vol. 254, 1979, pages 4022 - 4026
   DE BHEGUY ALEOPOLD PLWASIF NKORST RJHACKETT NRCRYSTAL RG: "Intrapleural administration of a serotype 5 adeno-associated virus coding for alpha1-antitrypsin mediates persistent, high lung and serum levels of alpha1-antitrypsin", MOL THER, vol. 10, 2004, pages 1003 - 1010
   PAGOVICH OEWANG BCHIUCHIOLO MJKAMINSKY SMSONDHI DJOSE CLPRICE CCBROOKS SFMEZEY JGCRYSTAL RG: "Anti-hlgE gene therapy of peanut-induced anaphylaxis in a humanized murine model of peanut allergy", J ALLERGY CLIN IMMUNOL, vol. 138, 2016, pages 1652 - 1662
   BRANTLY MNUKIWA TCRYSTAL RG: "Molecular basis of alpha-1-antitrypsin deficiency", AM J MED, vol. 84, 1988, pages 13 - 31
   BRANTLY MLPAUL LDMILLER BHFALK RTWU MCRYSTAL RG: "Clinical features and history of the destructive lung disease associated with alpha-1-antitrypsin deficiency of adults with pulmonary symptoms", AM REV RESPIR DIS, vol. 138, 1988, pages 327 - 336
   JALLAT S, TESSIER LH, BENAVENTE A, CRYSTAL RG, COURTNEY M: "Antiprotease targeting: altered specificity of alpha 1-antitrypsin by amino acid replacement at the reactive centre", REV FR TRANSFUS IMMUNOHEMATOL, vol. 29, 1986, pages 287 - 298
   CRYSTAL RG: "Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy", J CLIN INVEST, vol. 85, 1990, pages 1343 - 1352
   GADEK JEFELLS GAZIMMERMAN RLRENNARD SICRYSTAL RG: "Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema", J CLIN INVEST, vol. 68, 1981, pages 889 - 898
   LUNGARELLA GCAVARRA ELUCATTELLI MMARTORANA PA: "The dual role of neutrophil elastase in lung destruction and repair", INT J BIOCHEM CELL BIOL, vol. 40, 2008, pages 1287 - 1296
   SILVERMAN EKSANDHAUS RA: "Clinical practice. Alpha1-antitrypsin deficiency", N ENGL J MED, vol. 360, 2009, pages 2749 - 2757
   CRYSTAL RGBRANTLY MLHUBBARD RCCURIEL DTSTATES DJHOLMES MD: "The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy", CHEST, vol. 95, 1989, pages 196 - 208
   TUDER RMJANCIAUSKIENE SMPETRACHE I: "Lung disease associated with alpha1-antitrypsin deficiency", PROC AM THORAC SOC, vol. 7, 2010, pages 381 - 386
   GADEK JEKLEIN HGHOLLAND PVCRYSTAL RG: "Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects", J CLIN INVEST, vol. 68, 1981, pages 1158 - 1165
   WEWERS MDCASOLARO MASELLERS SESWAYZE SCMCPHAUL KMWITTES JT: "Crystal RG. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema", N ENGL J MED, vol. 316, 1987, pages 1055 - 1062
   CHAPMAN KRBURDON JGPIITULAINEN ESANDHAUS RASEERSHOLM NSTOCKS JMSTOEL BCHUANG LYAO ZEDELMAN JM: "Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial", LANCET, vol. 386, 2015, pages 360 - 368
   CRYSTAL RG: "Augmentation treatment for alpha1 antitrypsin deficiency", LANCET, vol. 386, 2015, pages 318 - 320
   CRYSTAL RG: "Compelling evidence for the efficacy of alpha1-antitrypsin augmentation treatment for alpha1-antitrypsin deficiency", LANCET RESPIR MED, vol. 5, 2017, pages 7 - 8
   MCELVANEY NGBURDON JHOLMES MGLANVILLE AWARK PATHOMPSON PJHERNANDEZ PCHLUMSKY JTESCHLER HFICKER JH: "Rapid Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE).", LANCET RESPIR MED, vol. 5, 2017, pages 51 - 60
   CHIUCHIOLO MJKAMINSKY SMSONDHI DHACKETT NRROSENBERG JBFRENK EZHWANG YVAN DE GRAAF BGHUTT JAWANG G: "Intrapleural administration of an AAVrh.10 vector coding for human alpha1-antitrypsin for the treatment of alpha1-antitrypsin deficiency", HUM GENE THER CLIN DEV, vol. 24, 2013, pages 161 - 173
   CHULAY JDYE GJTHOMAS DLKNOP DRBENSON JMHUTT JAWANG GHUMPHRIES MFLOTTE TR: "Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method", HUM GENE THER, vol. 22, 2011, pages 155 - 165
   CONLON TJCOSSETTE TERGER KCHOI YKCLARKE TSCOTT-JORGENSEN MSONG SCAMPBELL-THOMPSON MCRAWFORD JFLOTTE TR: "Efficient hepatic delivery and expression from a recombinant adeno-associated virus 8 pseudotyped alpha1-antitrypsin vector", MOL THER, vol. 12, 2005, pages 867 - 875
   DE BPHEGUY AHACKETT NRFERRIS BLEOPOLD PLLEE JPIERRE LGAO GWILSON JMCRYSTAL RG: "High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses", MOL THER, vol. 13, 2006, pages 67 - 76
   FLOTTE TRCONLON TJPOIRIER ACAMPBELL-THOMPSON MBYRNE BJ: "Preclinical characterization of a recombinant adeno-associated virus type 1-pseudotyped vector demonstrates dose-dependent injection site inflammation and dissemination of vector genomes to distant sites", HUM GENE THER, vol. 18, 2007, pages 245 - 256
   HALBERT CLMADTES DKVAUGHAN AEWANG ZSTORB RTAPSCOTT SJMILLER AD: "Expression of human alpha1-antitrypsin in mice and dogs following AAV6 vector-mediated gene transfer to the lungs", MOL THER, vol. 18, 2010, pages 1165 - 1172
   LIMBERIS MP WILSON JM: "Adeno-associated virus serotype 9 vectors transduce murine alveolar and nasal epithelia and can be readministered", PROC NATL ACAD SCI U S A, vol. 103, 2006, pages 12993 - 12998
   LIMBERIS MPVANDENBERGHE LHZHANG LPICKLES RJWILSON JM: "Transduction efficiencies of novel AAV vectors in mouse airway epithelium in vivo and human ciliated airway epithelium in vitro", MOL THER, vol. 17, 2009, pages 294 - 301
   LU YCHOI YKCAMPBELL-THOMPSON MLI CTANG QCRAWFORD JMFLOTTE TRSONG S: "Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector", J GENE MED, vol. 8, 2006, pages 730 - 735
   SONG SMORGAN MELLIS TPOIRIER ACHESNUT KWANG JBRANTLY MMUZYCZKA NBYRNE BJATKINSON M: "Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors", PROC NATL ACAD SCI U S A, vol. 95, 1998, pages 1434 - 1438
   VIRELLA-LOWELL IZUSMAN BFOUST KLOILER SCONLON TSONG SCHESNUT KAFERKOL TFLOTTE TR: "Enhancing rAAV vector expression in the lung", J GENE MED, vol. 7, 2005, pages 842 - 850
   XIAO WBERTA SCLU MMMOSCIONI ADTAZELAAR JWILSON JM: "Adeno-associated virus as a vector for liver-directed gene therapy", J VIROL, vol. 72, 1998, pages 10222 - 10226
   BEATTY KBIETH JTRAVIS J: "Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin", J BIOL CHEM, vol. 255, 1980, pages 3931 - 3934
   CARP HJANOFF A: "Potential mediator of inflammation. Phagocyte-derived oxidants suppress the elastase-inhibitory capacity of alpha 1-proteinase inhibitor in vitro", J CLIN INVEST, vol. 66, 1980, pages 987 - 995
   COHEN AB JAMES HL: "Reduction of the elastase inhibitory capacity of alpha 1-antitrypsin by peroxides in cigarette smoke: an analysis of brands and filters", AM REV RESPIR DIS, 1982, pages 126
   EVANS MD PRYOR WA: "Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor", AM J PHYSIOL, vol. 266, 1994, pages L593 - L611
   MATHESON NRWONG PSTRAVIS J: "Enzymatic inactivation of human alpha-1-proteinase inhibitor by neutrophil myeloperoxidase", BIOCHEM BIOPHYS RES COMMUN, vol. 88, 1979, pages 402 - 409
   SCOTT LJRUSSELL GLNIXON NBDAWES PTMATTEY DL: "Oxidation of alpha1-proteinase inhibitor by the myeloperoxidase-hydrogen peroxidase system promotes binding to immunoglobulin A", BIOCHEM BIOPHYS RES COMMUN, vol. 255, 1999, pages 562 - 567
   SUMMERS FAMORGAN PEDAVIES MJHAWKINS CL: "Identification of plasma proteins that are susceptible to thiol oxidation by hypochlorous acid and N-chloramines", CHEM RES TOXICOL, vol. 21, 2008, pages 1832 - 1840
   TAGGART CCERVANTES-LAUREAN DKIM GMCELVANEY NGWEHR NMOSS JLEVINE RL: "Oxidation of either methionine 351 or methionine 358 in alpha 1-antitrypsin causes loss of anti-neutrophil elastase activity", J BIOL CHEM, vol. 275, 2000, pages 27258 - 27265
   ELLIOTT PRLOMAS DACARRELL RWABRAHAMS JP: "Inhibitory conformation of the reactive loop of alpha 1-antitrypsin", NAT STRUCT BIOL, vol. 3, 1996, pages 676 - 681
   JANOFF ACARP HLEE DKDREW RT: "Cigarette smoke inhalation decreases alpha 1-antitrypsin activity in rat lung", SCIENCE, vol. 206, 1979, pages 1313 - 1314
   COURTNEY MJALLAT STESSIER LHBENAVENTE ACRYSTAL RGLECOCQ JP: "Synthesis in E. coli of alpha 1-antitrypsin variants of therapeutic potential for emphysema and thrombosis", NATURE, vol. 313, 1985, pages 149 - 151
   STRAUS SDFELLS GAWEWERS MDCOURTNEY MTESSIER LHTOLSTOSHEV PLECOCQ JPCRYSTAL RG: "Evaluation of recombinant DNA-directed E.coli produced alpha 1-antitrypsin as an anti-neutrophil elastase for potential use as replacement therapy of alpha 1-antitrypsin deficiency", BIOCHEM BIOPHYS RES COMMUN, vol. 130, 1985, pages 1177 - 1184
   DURANTON J BIETH JG: "Inhibition of proteinase 3 by [alpha] 1 -antitrypsin in vitro predicts very fast inhibition in vivo", AM J RESPIR CELL MOL BIOL, vol. 29, 2003, pages 57 - 61
   SPENCER LTPAONE GKREIN PMROUHANI FNRIVERA-NIEVES JBRANTLY ML: "Role of human neutrophil peptides in lung inflammation associated with alpha1-antitrypsin deficiency", AM J PHYSIOL LUNG CELL MOL PHYSIOL, vol. 286, 2004, pages L514 - L520
   PETRACHE IFIJALKOWSKA IMEDLER TRSKIRBALL JCRUZ PZHEN LPETRACHE HIFLOTTE TRTUDER RM.: "a-1 Antitrypsin Inhibits Caspase-3 Activity, Preventing Lung Endothelial Cell Apoptosis", AM J PATHOL, vol. 169, 2006, pages 1155 - 1166
   JANCIAUSKIENE SMNITA IMSTEVENS T: "Alpha1-antitrypsin, old dog, new tricks. Alpha1-antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP", J BIOL CHEM, vol. 282, 2007, pages 8573 - 8582
   BERGIN DAREEVES EPMELEADY PHENRY MMCELVANEY OJCARROLL TPCONDRON CCHOTIRMALL SHCLYNES MO'NEILL SJ: "alpha-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8", J CLIN INVEST, vol. 120, 2010, pages 4236 - 4250
   SHAHAF GMOSER HOZERI EMIZRAHI MABECASSIS ALEWIS EC: "alpha-1-antitrypsin gene delivery reduces inflammation, increases T-regulatory cell population size and prevents islet allograft rejection", MOL MED, vol. 17, 2011, pages 1000 - 1011
   LEWIS EC: "Expanding the clinical indications for alpha(1)-antitrypsin therapy", MOL MED, vol. 18, 2012, pages 957 - 970
   JONIGK DAL-OMARI MMAEGEL LMULLER MIZYKOWSKI NHONG JHONG KKIM SHDORSCH MMAHADEVA R: "Anti-inflammatory and immunomodulatory properties of alpha1-antitrypsin without inhibition of elastase", PROC NATL ACAD SCI U S A, vol. 119, 2013, pages 15007 - 15012
   BERGIN DAREEVES EPHURLEY KWOLFE RJAMEEL RFITZGERALD SMCELVANEY NG: "The circulating proteinase inhibitor alpha-1 antitrypsin regulates neutrophil degranulation and autoimmunity", SCI TRANSL MED, vol. 6, 2014, pages 217ra1
   EHLERS MR: "Immune-modulating effects of alpha-1 antitrypsin", BIOL CHEM, vol. 395, 2014, pages 1187 - 1193
   GERAGHTY PEDEN EPILLAI MCAMPOS MMCELVANEY NGFORONJY RF: "alpha1-Antitrypsin activates protein phosphatase 2A to counter lung inflammatory responses", AM J RESPIR CRIT CARE MED, vol. 190, 2014, pages 1229 - 1242
   GUYOT NWARTELLE JMALLERET LTODOROV AADEVOUASSOUX GPACHECO YJENNE DEBELAAOUAJ A: "Unopposed cathepsin G, neutrophil elastase, and proteinase 3 cause severe lung damage and emphysema", AM J PATHOL, vol. 184, 2014, pages 2197 - 2100
   KANER ZOCHAYON DESHAHAF GBARANOVSKI BMBAHAR NMIZRAHI MLEWIS EC: "Acute Phase Protein alpha1-Antitrypsin Reduces the Bacterial Burden in Mice by Selective Modulation of Innate Cell Responses", J INFECT DIS, vol. 211, 2015, pages 1489 - 1498
   SINDEN NJBAKER MJSMITH DJKREFT JUDAFFORN TRSTOCKLEY RA: "alpha-1-antitrypsin variants and the proteinase/antiproteinase imbalance in chronic obstructive pulmonary disease", AM J PHYSIOL LUNG CELL MOL PHYSIOL, vol. 308, 2015, pages L179 - L190
   ALAM SLI ZJANCIAUSKIENE SMAHADEVA R: "Oxidation of Z alpha1-antitrypsin by cigarette smoke induces polymerization: a novel mechanism of early-onset emphysema", AM J RESPIR CELL MOL BIOL, vol. 45, 2011, pages 261 - 269
   LOCKETT ADVAN DEMARK MGU YSCHWEITZER KSSIGUA NKAMOCKI KFIJALKOWSKA IGARRISON JFISHER AJSERBAN K: "Effect of cigarette smoke exposure and structural modifications on the alpha-1 Antitrypsin interaction with caspases", MOL MED, vol. 19, 2012, pages 445 - 454
   ALAM SLI ZATKINSON CJONIGK DJANCIAUSKIENE SMAHADEVA R: "Z alpha1-antitrypsin confers a proinflammatory phenotype that contributes to chronic obstructive pulmonary disease", AM J RESPIR CRIT CARE MED, vol. 189, 2014, pages 909 - 931
   "The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha 1-antitrypsin. The Alpha-1-Antitrypsin Deficiency Registry Study Group", AM J RESPIR CRIT CARE MED, vol. 158, 1998, pages 49 - 59
   LOMAS DA PARFREY H: "Alpha1-antitrypsin deficiency", 4: MOLECULAR PATHOPHYSIOLOGY. THORAX, vol. 59, 2004, pages 529 - 535
   TANASH HANILSSON PMNILSSON JAPIITULAINEN E: "Survival in severe alpha-1-antitrypsin deficiency (PiZZ", RESPIR RES, vol. 11, 2010, pages 44
   DE SERRES FJBLANCO I: "Prevalence of alpha1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: a comprehensive review", THER ADV RESPIR DIS, vol. 6, 2012, pages 277 - 295
   PERLMUTTER DH SILVERMAN GA: "Hepatic fibrosis and carcinogenesis in alpha1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders", COLD SPRING HARB PERSPECT BIOL, vol. 3, 2011, pages a005801
   TOPIC ALJUJIC MRADOJKOVIC D: "Alpha-1-antitrypsin in pathogenesis of hepatocellular carcinoma", HEPAT MON, vol. 12, 2012, pages e7042
   INATY H ARABELOVIC S: "alpha1-Antitrypsin deficiency in a patient diagnosed with granulomatosis with polyangiitis", BMJ CASE REP, 2013, pages 2013
   TECKMAN JH: "Liver disease in alpha-1 antitrypsin deficiency: current understanding and future therapy", COPD, vol. 1, 2013, pages 35 - 43
   ALBERICI FMARTORANA DVAGLIO A: "Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis", NEPHROL DIAL TRANSPLANT, vol. 30, 2014, pages i37 - i45
   DE SERRES FBLANCO I: "Role of alpha-1 antitrypsin in human health and disease", J INTERN MED, vol. 276, 2014, pages 311 - 335
   STONE HPYE ASTOCKLEY RA: "Disease associations in alpha-1-antitrypsin deficiency", RESPIR MED, vol. 108, 2014, pages 338 - 343
   DUVOIX AROUSSEL BDLOMAS DA: "Molecular pathogenesis of alpha-1-antitrypsin deficiency", REV MAL RESPIR, vol. 31, 2014, pages 992 - 1002
   GREENE CMMILLER SDCARROLL TMCLEAN CO'MAHONY MLAWLESS MWO'NEILL SJTAGGART CCMCELVANEY NG: "Alpha-1 antitrypsin deficiency: a conformational disease associated with lung and liver manifestations", J INHERIT METAB DIS, vol. 31, 2008, pages 21 - 34
   MORNEX JFCHYTIL-WEIR AMARTINET YCOURTNEY MLECOCQ JPCRYSTAL RG: "Expression of the alpha-1-antitrypsin gene in mononuclear phagocytes of normal and alpha-1-antitrypsin-deficient individuals", J CLIN INVEST, vol. 77, 1986, pages 1952 - 1961
   VAN 'T WOUT EFVAN SCHADEWIJK ASAVAGE NDSTOLK JHIEMSTRA PS: "alpha1-antitrypsin production by proinflammatory and antiinflammatory macrophages and dendritic cells", AM J RESPIR CELL MOL BIOL, vol. 46, 2012, pages 365 - 376
   DU BOIS RMBERNAUDIN JFPAAKKO PHUBBARD RTAKAHASHI HFERRANS VCRYSTAL RG: "Human neutrophils express the alpha 1-antitrypsin gene and produce alpha 1-antitrypsin", BLOOD, vol. 77, 1991, pages 2724 - 2730
   VENEMBRE PBOUTTEN ASETA NDEHOUX MSCRESTANI BAUBIER MDURAND G: "Secretion of alpha 1-antitrypsin by alveolar epithelial cells", FEBS LETT, vol. 346, 1994, pages 171 - 174
   CICHY JPOTEMPA JTRAVIS J: "Biosynthesis of alpha1-proteinase inhibitor by human lung-derived epithelial cells", J BIOL CHEM, vol. 272, 1997, pages 8250 - 8255
   GEBOES KRAY MBRUTGEERTS PCALLEA FDESMET VJVANTRAPPEN G: "Morphological identification of alpha-l-antitrypsin in the human small intestine", HISTOPATHOLOGY, vol. 6, 1982, pages 55 - 60
   PERLMUTTER DHDANIELS JDAUERBACH HSDE SCHRYVER-KECSKEMETI KWINTER HSALPERS DH: "The alpha 1-antitrypsin gene is expressed in a human intestinal epithelial cell line", J BIOL CHEM, vol. 264, 1989, pages 9485 - 9490
   COX DWMARKOVIC VDTESHIMA IE: "Genes for immunoglobulin heavy chains and for alpha 1-antitrypsin are localized to specific regions of chromosome 14q", NATURE, vol. 297, 1982, pages 428 - 430
   SCHROEDER WTMILLER MFWOO SLSAUNDERS GF: "Chromosomal localization of the human alpha 1-antitrypsin gene (PI) to 14q31-32", AM J HUM GENET, vol. 37, 1985, pages 868 - 872
   LAURELL C-B ERIKSSON S: "The electrophoretic alpha1-globulin pattern of serum in alpha1-antitrypsin deficiency", SCAND J CLIN LAB INVEST, vol. 15, 1963, pages 132 - 140
   SEIXAS SGARCIA OTROVOADA MJSANTOS MTAMORIM AROCHA J: "Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism", HUM GENET, vol. 108, 2001, pages 20 - 30
   STOLLER JK ABOUSSOUAN LS: "A review of alpha1-antitrypsin deficiency", AM J RESPIR CRIT CARE MED, vol. 185, 2012, pages 246 - 259
   KURACHI KCHANDRA TDEGEN SJWHITE TTMARCHIORO TLWOO SLDAVIE EW: "Cloning and sequence of cDNA coding for alpha 1-antitrypsin", PROC NATL ACAD SCI U S A, vol. 78, 1981, pages 6826 - 6830
   JEPPSSON JO: "Amino acid substitution Glu leads to Lys alpha1-antitrypsin PiZ", FEBS LETT, vol. 65, 1976, pages 195 - 197
   BIRRER PMCELVANEY NGCHANG-STROMAN LMCRYSTAL RG: "Alpha 1-antitrypsin deficiency and liver disease", J INHERIT METAB DIS, vol. 14, 1991, pages 512 - 525
   GOOPTU B LOMAS DA: "Conformational pathology of the serpins: themes, variations, and therapeutic strategies", ANNU REV BIOCHEM, vol. 78, 2009, pages 147 - 176
   LOMAS DAEVANS DLFINCH JTCARRELL RW: "The mechanism of Z alpha 1-antitrypsin accumulation in the liver", NATURE, vol. 357, 1992, pages 605 - 607
   NUKIWA TSATOH KBRANTLY MLOGUSHI FFELLS GACOURTNEY MCRYSTAL RG: "Identification of a second mutation in the protein-coding sequence of the Z type alpha 1-antitrypsin gene", J BIOL CHEM, vol. 261, 1986, pages 15989 - 15994
   LONG GLCHANDRA TWOO SLDAVIE EWKURACHI K: "Complete sequence of the cDNA for human alpha 1-antitrypsin and the gene for the S variant", BIOCHEMISTRY, vol. 23, 1984, pages 4828 - 4837
   OWEN MCCARRELL RWBRENNAN SO: "The abnormality of the S variant of human alpha-1-antitrypsin", BIOCHIM BIOPHYS ACTA, vol. 453, 1976, pages 257 - 261
   YOSHIDA AEWING CWESSELS MLIEBERMAN JGAIDULIS L: "Molecular abnormality of PI S variant of human alpha1-antitrypsin", AM J HUM GENET, vol. 29, 1977, pages 233 - 239
   OGUSHI FHUBBARD RCFELLS GACASOLARO MACURIEL DTBRANTLY MLCRYSTAL RG: "Evaluation of the S-type of alpha-1-antitrypsin as an in vivo and in vitro inhibitor of neutrophil elastase", AM REV RESPIR DIS, vol. 137, 1988, pages 364 - 370
   BORNHORST JAGREENE DNASHWOOD ERGRENACHE DG: "alpha1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population", CHEST, vol. 143, 2013, pages 1000 - 1008
   FDA, B. P. A. C, 2017
   "American Thoracic S European Respiratory S. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency", AM J RESPIR CRIT CARE MED, vol. 168, 2003, pages 818 - 900
   THOMPSON HEALTHCARE, RED BOOK: PHARMACY'S FUNDAMENTAL REFERENCE, 2010
   BERNSTEIN JAALEXIS NBARNES CBERNSTEIN ILBERNSTEIN JANEL APEDEN DDIAZ-SANCHEZ DTARLO SMWILLIAMS PB: "Health effects of air pollution", J ALLERGY CLIN IMMUNOL, vol. 114, 2004, pages 1116 - 1123
   CIENCEWICKI J, TRIVEDI S, KLEEBERGER SR: "Oxidants and the pathogenesis of lung disease", J ALLERGY CLIN IMMUNOL, vol. 122, 2008, pages 456 - 468
   CHIUCHIOLO MJ CRYSTAL RG: "Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease", ANN AM THORAC SOC, vol. 13, 2016, pages S352 - S369
   GARVER RI, JRCHYTIL ACOURTNEY MCRYSTAL RG: "Clonal gene therapy: transplanted mouse fibroblast clones express human alpha 1-antitrypsin gene in vivo", SCIENCE, vol. 237, 1987, pages 762 - 764
   ROSENFELD MASIEGFRIED WYOSHIMURA KYONEYAMA KFUKAYAMA MSTIER LEPAAKKO PKGILARDI PSTRATFORD-PERRICAUDET LDPERRICAUDET M: "Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo", SCIENCE, vol. 252, 1991, pages 431 - 434
   DAYA S BERNS KL: "Gene therapy using adeno-associated virus vectors", CLIN MICROBIOL REV, vol. 21, 2008, pages 583 - 593
   GAO GVANDENBERGHE LHALVIRA MRLU YCALCEDO RZHOU XWILSON JM: "Clades of adeno-associated viruses are widely disseminated in human tissues", J VIROL, vol. 78, 2004, pages 56381 - 6388
   ASOKAN A, SCHAFFER DV, JUDE SR: "The AAV Vector Toolkit: Poised at the Clinical Crossroads", MOL THER, vol. 20, 2012, pages 699 - 708
   NIWA H, YAMAMURA K, MIYAZAKI J: "Efficient selection for high-expression transfectants with a novel eukaryotic vector", GENE, vol. 108, 1991, pages 193 - 199
   CARRELL ROWEN MBRENNAN SVAUGHAN L: "Carboxy terminal fragment of human alpha-1-antitrypsin from hydroxylamine cleavage: homology with antithrombin III", BIOCHEM BIOPHYS RES COMMUN, vol. 91, 1979, pages 1032 - 1037
   CARRELL RW, JEPPSSON JO, LAURELL CB, BRENNAN SO, OWEN MC, VAUGHAN L, BOSWELL DR.: "Structure and variation of human alpha 1-antitrypsin", NATURE, vol. 298, 1982, pages 329 - 334
   LOEBERMANN H, TOKUOKA R, DEISENHOFER J, HUBER R: " Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function", J MOL BIOL, vol. 177, 1984, pages 531 - 557
   BUHL R, MEYER A, VOGELMEIER C: "Oxidant-protease interaction in the lung. Prospects for antioxidant therapy", CHEST, vol. 110, 1996, pages 267S - 272S
   RODRIGUEZ-PANADERO F MONTES-WORBOYS A: "Mechanisms of pleurodesis", RESPIRATION, vol. 83, 2012, pages 91 - 98
   LI ZALAM SWANG JSANDSTROM CSJANCIAUSKIENE SMAHADEVA R: "Oxidized {alpha}1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema", AM J PHYSIOL LUNG CELL MOL PHYSIOL, vol. 297, 2009, pages L388 - L400
   MORAGA F JANCIAUSKIENE S. A: " Activation of primary human monocytes by the oxidized form of alpha1-antitrypsin", J BIOL CHEM, vol. 275, 2000, pages 7693 - 7700
   UEDA MMASHIBA SUCHIDA K: "Evaluation of oxidized alpha-1-antitrypsin in blood as an oxidative stress marker using anti-oxidative alpha1-AT monoclonal antibody", CLIN CHIM ACTA, vol. 317, 2002, pages 125 - 131
   ROSENBERG S, BARR PJ, NAJARIAN RC, HALLEWELL RA.: "Synthesis in yeast of a functional oxidation-resistant mutant of human alpha-antitrypsin", NATURE, vol. 312, 1984, pages 77 - 80
   NUKIWA, TOGUSHI, FCRYSTAL, R. G: "Alpha 1-antitrypsin deficiency", 1996, MARCEL DEKKER, INC., pages: 33 - 43
   ELLIOTT PRPEI XYDAFFORN TRLOMAS DA: "Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease", PROTEIN SCI, vol. 9, 2000, pages 1274 - 1281
   GADEK JE, FELLS GA, CRYSTAL RG: " Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans", SCIENCE, vol. 206, 1979, pages 1315 - 1316
   BALS RXIAO WSANG NWEINER DJMEEGALLA RLWILSON JM: "Transduction of well-differentiated airway epithelium by recombinant adeno-associated virus is limited by vector entry", J VIROL, vol. 73, 1999, pages 6085 - 6088
   YANG YLI QERTL HCWILSON JM: "Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses", J VIROL, vol. 69, 1995, pages 2004 - 2015
   FERRARI S, GRIESENBACH U, GEDDES DM, ALTON E.: "Immunological hurdles to lung gene therapy", CLIN EXP IMMUNOL, vol. 132, 2003, pages 1 - 8
   DUAN DYUE YYAN ZMCCRAY PB, JRENGELHARDT JF: "Polarity influences the efficiency of recombinant adenoassociated virus infection in differentiated airway epithelia", HUM GENE THER, vol. 9, 1998, pages 2761 - 2776
   LIQUN WANG R, MCLAUGHLIN T, COSSETTE T, TANG Q, FOUST K, CAMPBELL-THOMPSON M, MARTINO A, CRUZ P, LOILER S, MUELLER C, FLOTTE TR: "Recombinant AAV serotype and capsid mutant comparison for pulmonary gene transfer of alpha-1-antitrypsin using invasive and noninvasive delivery", MOL THER, vol. 17, 2009, pages 81 - 87
   YU HBUFF SMBAATZ JEVIRELLA-LOWELL I: "Oral instillation with surfactant phospholipid: a reliable alternative to intratracheal injection in mouse studies", LAB ANIM, vol. 42, 2008, pages 294 - 304
   SONG, S., SCOTT-JORGENSEN, M., WANG, J., POIRIER, A., CRAWFORD, J., CAMPBELL-THOMPSON, M.,FLOTTE, T.R., UNITED STATES, 2002
   CONLON TJCALCEDO RBETTS MRSPENCER CBYRNE BJWILSON JMFLOTTE TR: "Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy", PROC NATL ACAD SCI U S A, vol. 106, 2009, pages 16363 - 16368
   FLOTTE TRTRAPNELL BCHUMPHRIES MCAREY BCALCEDO RROUHANI FCAMPBELL-THOMPSON MYACHNIS ATSANDHAUS RAMCELVANEY NG: "Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing alpha1-antitrypsin: interim re", HUM GENE THER, vol. 22, 2011, pages 1239 - 1247
   MUELLER CCHULAY JDMCELVANEY NGGERNOUX GREEVES EPROUHANI FNHUMPHRIES MGRUNTMAN AMCAMPBELL-THOMPSON MWILSON JM: "Sustained expression with partial correctionof neurtrophil defects 5 years after intramuscular rAAV1 gene therapy for alpha-1 antitrypsin deficiency", MOL THER, vol. 24, 2016, pages S11 - S12
   HEGUY A CRYSTAL RG: "Intrapleural 'outside-in' gene therapy: therapeutics for organs of the chest via gene transfer to the pleura", CURRENT OPINION IN MOLECULAR THERAPEUTICS, vol. 7, 2005, pages 440 - 453
   MAE M CRYSTAL RG: "Gene transfer to the pleural mesothelium as a strategy to deliver proteins to the lung parenchyma ", HUM GENE THER, vol. 13, 2002, pages 1471 - 1482
   FINLEY DJ RUSCH VW: "Anatomy of the pleura", THORAC SURG CLIN, vol. 21, 2011, pages 157 - 163
   WANG NS: "Anatomy and physiology of the pleural space", CLIN CHEST MED, vol. 6, 1985, pages 3 - 16
   RENNARD SI, JAURAND MC, BIGNON J, KAWANAMI O, FERRANS VJ, DAVIDSON J, CRYSTAL RG.: "Role of pleural mesothelial cells in the production of the submesothelial connective tissue matrix of lung", AM REV RESPIR DIS, vol. 130, 1984, pages 267 - 274
   AGOSTONI EZOCCHI L: "Pleural liquid and its exchanges", RESPIR PHYSIOL NEUROBIOL, vol. 159, 2007, pages 311 - 323
   NOPPEN M: "Normal volume and cellular contents of pleural fluid", CURR OPIN PULM MED, vol. 7, 2001, pages 180 - 182
   MUTSAERS SE: " Mesothelial cells: their structure, function and role in serosal repair.", RESPIROLOGY, vol. 7, 2002, pages 171 - 191
   NOPPEN MDE WAELE MLI RGUCHT KVD'HAESE JGERLO EVINCKEN W: "Volume and cellular content of normal pleural fluid in humans examined by pleural lavage", AM J RESPIR CRIT CARE MED, vol. 162, 2000, pages 1023 - 1026
   NEGRINI D MORIONDO A: "Pleural function and lymphatics", ACTA PHYSIOL (OXF, vol. 207, 2013, pages 244 - 259
   VAN DEN HEUVEL MM, SMIT HJ, BARBIERATO SB, HAVENITH CE, BEELEN RH, POSTMUS PE.: "Talc-induced inflammation in the pleural cavity", EUR RESPIR J, vol. 12, 1998, pages 1419 - 1423
   CANTIN ACRYSTAL RG: "Oxidants, antioxidants and the pathogenesis of emphysema", EUR J, vol. 139, 1985, pages 7 - 17
   CROSS CE, VAN D, V, O'NEILL CA, LOUIE S, HALLIWELL B: "Oxidants, antioxidants, and respiratory tract lining fluids", ENVIRON HEALTH PERSPECT, vol. 10, 1994, pages 185 - 191
   WOZNIAK JWANDTKE TKOPINSKI PCHOROSTOWSKA-WYNIMKO J: "Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy", HUM GENE THER, vol. 26, 2015, pages 609 - 718
   MORAGA F, LINDGREN S, JANCIASKIENE S: "Effects of noninhibitory alpha-1-antitrypsin on primary human monocyte activation in vitro", ARCH BIOCHEM BIOPHYS, vol. 386, 2001, pages 221 - 226
   DARNELL RB, FERRANTE RJ, FILLIT H, FINKELSTEIN R, FISHER M, GENDELMAN HE, GOLUB RM, GOUDREAU JL, GROSS RA, GUBITZ AK, HESTERLEE SE: "A call for transparent reporting to optimize the predictive value of preclinical research", NATURE, vol. 490, 2012, pages 187 - 191
   HUBBARD RCOGUSHI FFELLS GACANTIN AMJALLAT SCOURTNEY MCRYSTAL RG: "Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactivate the active site of alpha 1-antitrypsin, rendering it ineffective as an inhibitor of neutrophil elastase", J CLIN INVEST, vol. 80, 1987, pages 1289 - 1295
   GRIFFITHS SW COONEY CL: "Relationship between protein structure and methionine oxidation in recombinant human alpha 1-antitrypsin", BIOCHEMISTRY, vol. 41, 2002, pages 6245 - 6252
   BRANTLY MLWITTES JTVOGELMEIER CFHUBBARD RCFELLS GACRYSTAL RG: "Use of a highly purified alpha 1-antitrypsin standard to establish ranges for the common normal and deficient alpha 1-antitrypsin phenotypes", CHEST, 1991, pages 100
   PADRINES MSCHNEIDER-POZZER MBIETH JG: "Inhibition of neutrophil elastase by alpha-1-proteinase inhibitor oxidized by activated neutrophils", AM REV RESPIR DIS, vol. 139, 1989, pages 783 - 790
   JALLAT SCARVALLO DTESSIER LHROECKLIN DROITSCH COGUSHI FCRYSTAL RG: "Courtney M. Altered specificities of genetically engineered alpha 1 antitrypsin variants", PROTEIN ENG, vol. 1, 1986, pages 29 - 35
   TRAVIS JMATHESON NRGEORGE PMCARRELL RW: "Kinetic studies on the interaction of alpha 1-proteinase inhibitor (Pittsburgh) with trypsin-like serine proteinases", BIOL CHEM HOPPE SEYLER, vol. 367, 1986, pages 853 - 859
   BOUDIER C, LAURENT P, BIETH JG.: "Leukoproteinases and pulmonary emphysema:cathepsin G and other chymotrypsin-like proteinases enhance the elastolytic activity of elastase on lung elastin ", ADV EXP MED BIOL, vol. 167, 1984, pages 313 - 317
   ADVERUM BIOTECHNOLOGIES, I., 2016
   MINGOZZI F HIGH KA: "Immune responses to AAV in clinical trials", CURR GENE THER, vol. 11, 2011, pages 321 - 330
   VAN DER LAAN LJWANG YTILANUS HWJANSSEN HLPAN Q: "AAV-mediated gene therapy for liver diseases: the prime candidate for clinical application?", EXPERT OPIN BIOL THER, vol. 11, 2011, pages 315 - 327
   MANNO CS, PIERCE GF, ARRUDA VR, GLADER B, RAGNI M, RASKO JJ, OZELO MC, HOOTS K,BLATT P, KONKLE B, DAKE M, KAYE R, RAZAVI M, ZAJKO : "Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response", NAT MED, vol. 12, 2006, pages 342 - 347
   SCHNEPP BCCHULAY JDYE GJFLOTTE TRTRAPNELL BCJOHNSON PR: "Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle", HUM GENE THER, vol. 27, 2016, pages 32 - 42
   SONDHI D, PETERSON DA, GIANNARIS EL, SANDERS CT, MENDEZ BS, DE B, ROSTKOWSKI AB,BLANCHARD B, BJUGSTAD K, SLADEK JR, JR., REDMOND D: "AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL", GENE THER, vol. 12, 2005, pages 1618 - 1632
   CHIUCHIOLO MJKAMINSKY SMSONDHI DMANCENIDO DHOLLMANN CCRYSTAL RG: "Phase I/II study of intrapleural administration of a serotype rh.10 replication-deficient adeno-associated virus gene transfer vector expressing the human alpha1-antitrypsin cDNA to individuals with alpha1-antitrypsin deficiency", HUM GENE THER CLIN DEV, vol. 25, 2014, pages 112 - 133
   RENNARD SI, BASSET G, LECOSSIER D, O'DONNELL KM, PINKSTON P, MARTIN PG, CRYSTAL RG.: "Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution", J APPL PHYSIOL, vol. 1986, no. 60, 1985, pages 532 - 538
   NATHWANI AC, TUDDENHAM EG, RANGARAJAN S, ROSALES C, MCINTOSH J, LINCH DC,CHOWDARY P, RIDDELL A, PIE AJ, HARRINGTON C, O'BEIRNE J, : "Adenovirus-associated virus vector-mediated gene transfer in hemophilia B", N ENGL J MED, vol. 365, 2011, pages 2357 - 2365
   MELIANI ALEBORGNE CTRIFFAULT SJEANSON-LEH LVERON PMINGOZZI F: "Determination of anti-adeno-associated virus vector neutralizing antibody titer with an in vitro reporter system", HUM GENE THER METHODS, vol. 26, 2015, pages 45 - 53
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