SG11201900366QA - Scalable high recovery methods for producing high yield recombinant adeno-associated viral (raav) vector and recombinant adeno-associated viral (raav) vectors produced thereby - Google Patents

Scalable high recovery methods for producing high yield recombinant adeno-associated viral (raav) vector and recombinant adeno-associated viral (raav) vectors produced thereby

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Publication number
SG11201900366QA
SG11201900366QA SG11201900366QA SG11201900366QA SG11201900366QA SG 11201900366Q A SG11201900366Q A SG 11201900366QA SG 11201900366Q A SG11201900366Q A SG 11201900366QA SG 11201900366Q A SG11201900366Q A SG 11201900366QA SG 11201900366Q A SG11201900366Q A SG 11201900366QA
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SG
Singapore
Prior art keywords
raav
international
recombinant adeno
rule
vector
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SG11201900366QA
Inventor
Guang Qu
John Fraser Wright
Younghoon Oh
Yuhuan Wang
Haibo Zhang
Laura Duncan
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Spark Therapeutics Inc
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Publication date
Application filed by Spark Therapeutics Inc filed Critical Spark Therapeutics Inc
Publication of SG11201900366QA publication Critical patent/SG11201900366QA/en

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    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
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    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
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    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • C12N7/02—Recovery or purification
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    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6472—Cysteine endopeptidases (3.4.22)
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    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/14—Dipeptidyl-peptidases and tripeptidyl-peptidases (3.4.14)
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/14—Type of nucleic acid interfering N.A.
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    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14151—Methods of production or purification of viral material

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 111111110111101110101011111011111011111111010111111111111011101111101111001111 Organization - - - ' International Bureau (10) International Publication Number (43) International Publication Date .....0\" WO 2018/017956 A3 25 January 2018 (25.01.2018) WI P0 I P C T (51) International Patent Classification: Pennsylvania 19010 (US). WANG, Yuhuan; 37 Buck- C12N 15/861 (2006.01) C07K 2/00 (2006.01) ingham Place, Cherry Hill, New Jersey 08003-2665 (US). C12N 7/00 (2006.01) Cl 2N 15/64 (2006.01) ZHANG, Haibo; 30 President Avenue, Rutledge, Penn- A61K 48/00 (2006.01) sylvania 19070 (US). DUNCAN, Laura; 50 South Valley (21) International Application Number: Road, Apt. G-06, Paoli, Pennsylvania 19301 (US). PCT/US2017/043291 (74) Agent: BEDGOOD, Robert M.; PILLSBURY WIN- THROP SHAW PITTMAN LLP, P.O. BOX 10500, (22) International Filing Date: McLean, Virginia 22102 (US). 21 July 2017 (21.07.2017) (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (26) Publication Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (30) Priority Data: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/365,312 21 July 2016 (21.07.2016) US DZ, EC, EE, EG, ES, FL GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (71) Applicant: SPARK THERAPEUTICS, INC. [US/US]; KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 3737 Market Street, Suite 1300, Philadelphia, Pennsylvania MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 19104 (US). OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (72) Inventors: QU, Guang; 22 Beaver Dam Drive, Sick-TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. lerville, New Jersey 08081 (US). WRIGHT, John Fras- er; 68 River Birch Circle, Princeton, New Jersey 08540 (84) Designated States (unless otherwise indicated, for every = = (US). OH, Younghoon; 766 Robinhood Road, Bryn Mawr, kind of regional protection available): ARIPO (BW, GH, = = (54) Title: SCALABLE HIGH RECOVERY METHODS FOR PRODUCING HIGH YIELD RECOMBINANT ADENO-ASSOCIAT- ED VIRAL (RAAV) VECTOR AND RECOMBINANT ADENO-ASSOCIATED VIRAL (RAAV) VECTORS PRODUCED THERE- = BY 1 17 95 6 A3 1 11 111 1111111111 111111 11111 1 1111111 111111 111111 1 111111111 11 11 A 5.00E+13 4.50E+13 4.00E+13 3.50E+13 2 ---- 3.00E+13 1 3 2.50E+13 '8 2.00E+13 1.50E+13 1.00E+13 5.00E+12 aopEioo \" , \..._....... ' \ ./ r' ‘ ‘..\ \., \ K ,,,,, titer (vg/mL) \ r---------------------- diameter ..- % -------- 35 • ‘`-% ' 30 2 • '\" r.. , E 20 8 1 2 1 n . ii 0 -- -- - -- - -- - - - - (nm) . fit 3000 sec-1 1.38E+13 ii t 3000 sec-1 : 35.77 11E10000 sec-Ii 4.81E+13 . IN 10000 sec-1. 36.47 1 Figure 1 ---.... Il © (57) : Provided are methods for producing recombinant adeno-associated virus (rAAV) vector particles at high recovery or ei high titer. Also provided are methods that concentrate rAAV vectors to a high concentration, for example, up to 5E+13 (5x10 13 ) vector C genomes per milliliter (Vg/ml) with little if any rAAV aggregates. [Continued on next page] WO 2018/017956 A3 IMEDIMOM0101011MERIONIMMIIHRIMODEfin GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(U)) — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) — of inventorship (Rule 4.17(iv)) Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) (88) Date of publication of the international search report: 08 March 2018 (08.03.2018)
SG11201900366QA 2016-07-21 2017-07-21 Scalable high recovery methods for producing high yield recombinant adeno-associated viral (raav) vector and recombinant adeno-associated viral (raav) vectors produced thereby SG11201900366QA (en)

Applications Claiming Priority (2)

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US201662365312P 2016-07-21 2016-07-21
PCT/US2017/043291 WO2018017956A2 (en) 2016-07-21 2017-07-21 Scalable high recovery methods for producing high yield recombinant adeno-associated viral (raav) vector and recombinant adeno-associated viral (raav) vectors produced thereby

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BR112018003665A2 (en) 2015-09-28 2018-09-25 Univ North Carolina Chapel Hill methods and compositions for antibody evasion viral vectors
AU2017315679B2 (en) 2016-08-23 2023-12-14 Akouos, Inc. Compositions and methods for treating non-age-associated hearing impairment in a human subject
CN110499287B (en) * 2019-08-30 2021-07-23 博雅干细胞科技有限公司 Method for simply preparing placenta mesenchymal stem cell exosome
MX2022004352A (en) 2019-10-17 2022-07-19 Stridebio Inc Adeno-associated viral vectors for treatment of niemann-pick disease type c.
KR102167829B1 (en) * 2020-02-10 2020-10-20 주식회사 이노테라피 Stabilizers for adeno-associated viruses and methods for stabilizing adeno-associated viruses using the Same
IL295747A (en) 2020-02-21 2022-10-01 Akouos Inc Compositions and methods for treating non-age-associated hearing impairment in a human subject
WO2023085382A1 (en) * 2021-11-12 2023-05-19 Ａｇｃ株式会社 Virus purification method
JP2023141423A (en) * 2022-03-24 2023-10-05 国立大学法人 東京大学 Virus purification method

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3290513T3 (en) * 2004-06-01 2022-12-12 Genzyme Corp COMPOSITIONS AND METHODS FOR PREVENTING AAV VECTOR AGGREGATION
AU2006215313B2 (en) * 2005-01-25 2011-11-24 Pfizer Ireland Pharmaceuticals Method for diafiltration
FR2884255B1 (en) * 2005-04-11 2010-11-05 Vivalis USE OF EBX AVIATION STEM CELL LINES FOR THE PRODUCTION OF INFLUENZA VACCINE
BRPI0908474A2 (en) * 2008-02-12 2016-07-26 Sanofi Pasteur Ltd methods of using ion exchange chromatography and gel filtration for chicken pox virus purification
US8202726B2 (en) * 2008-09-24 2012-06-19 Medimmune, Llc Methods for cultivating cells, propagating and purifying viruses
IN2012DN06629A (en) * 2010-01-28 2015-10-23 Philadelphia Children Hospital
CN107828820B (en) * 2010-10-27 2022-06-07 学校法人自治医科大学 Adeno-associated virus particles for gene transfer into nervous system cells
PL2970948T3 (en) * 2013-03-15 2019-06-28 Glaxosmithkline Biologicals Sa Rna purification methods
EP3054007A1 (en) * 2015-02-09 2016-08-10 Institut National De La Sante Et De La Recherche Medicale (Inserm) Recombinant adeno-associated virus particle purification comprising an immuno-affinity purification step

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IL264270A (en) 2019-02-28
DK3488007T3 (en) 2024-02-19
RU2019104759A3 (en) 2020-11-17
JP7153009B2 (en) 2022-10-13
EP3488007A2 (en) 2019-05-29
RU2019104759A (en) 2020-08-21
EP3488007B1 (en) 2023-12-20
IL301963A (en) 2023-06-01
MX2019000882A (en) 2019-08-12
KR20220162834A (en) 2022-12-08
BR112019001146A2 (en) 2019-04-30
RU2768045C2 (en) 2022-03-23
MY194198A (en) 2022-11-21
KR20190045174A (en) 2019-05-02
AU2017299779A1 (en) 2019-01-31
CA3031095A1 (en) 2018-01-25
CN109790549A (en) 2019-05-21
WO2018017956A2 (en) 2018-01-25
FI3488007T3 (en) 2024-03-19
AU2017299779B2 (en) 2021-12-02
JP2019524101A (en) 2019-09-05
EP3488007A4 (en) 2020-01-01
US20190284576A1 (en) 2019-09-19
PT3488007T (en) 2024-03-14

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