SG11201810210UA - Engineered botulinum neurotoxins - Google Patents

Engineered botulinum neurotoxins

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Publication number
SG11201810210UA
SG11201810210UA SG11201810210UA SG11201810210UA SG11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA SG 11201810210U A SG11201810210U A SG 11201810210UA
Authority
SG
Singapore
Prior art keywords
international
boston
pct
disclosed
substitution mutations
Prior art date
Application number
SG11201810210UA
Inventor
Sicai Zhang
Min Dong
Paul Stenmark
Original Assignee
Childrens Medical Center
Paul Stenmark
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Childrens Medical Center, Paul Stenmark filed Critical Childrens Medical Center
Publication of SG11201810210UA publication Critical patent/SG11201810210UA/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/33Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Clostridium (G)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/48Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886Metalloendopeptidases (3.4.24), e.g. collagenase
    • A61K38/4893Botulinum neurotoxin (3.4.24.69)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/10Drugs for disorders of the urinary system of the bladder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/24Metalloendopeptidases (3.4.24)
    • C12Y304/24069Bontoxilysin (3.4.24.69), i.e. botulinum neurotoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization 111111111111111111111111111111111111111111111111111111111111111111111111111111111111 International Bureau (10) International Publication Number (43) International Publication Date .....0\"\" WO 2017/214447 Al 14 December 2017 (14.12.2017) WIP0 I PCT (51) International Patent Classification: (74) Agent: EL-HAYEK, Roque; Wo1f, Greenfield & Sacks, C07K 14/33 (2006.01) A61K 38/48 (2006.01) P.c., 600 Atlantic Avenue, Boston, MA 02210-2206 (US). A61K 38/00 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: PCT/US2017/036628 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (22) International Filing Date: 08 June 2017 (08.06.2017) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, KP, KR, (25) Filing Language: English KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, 62/347,579 08 June 2016 (08.06.2016) US TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant. CHILDREN'S MEDICAL CENTER COR- (84) Designated States (unless otherwise indicated, for every PORATION [US/US]; 55 Shattuck Street, Boston, MA kind of regional protection available): ARIPO (BW, GH, 02115 (US). GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (72) Inventor; and UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (71) Applicant: STENMARK, Paul [SE/SE]; Svantearrhenius- EE, ES, FL FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, — vag 16c, 10691 Stockholm (SE). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, Inventors: ZHANG, Sicai; En 1070, 300 Longwood Ave, (72) TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, = Boston, MA (US). DONG, Min; 12 Croft Lane, Weatogue, CT 06089 (US). KM, ML, MR, NE, SN, TD, TG). = Title: ENGINEERED BOTULINUM NEUROTOXINS (54) = (57) : Disclosed herein are modified Clostridial Botulinum neurotoxin (BoNT) polypep- 3 tides with a modified receptor binding domain of Clostridial Botulinum serotype B, compris- = — ing one or more substitution mutations at positions corresponding 1248 or 1249 in serotype B, Z strain 1. Specific substitution mutations include I1248F, I1248Y, I1248H, I1248W, V1249W, = g g. V1249F, V1249Y, V1249H, I1248WN1249F, I1248WN1249Y, I1248WN1249H, I1248F/ = = = 1 V1249Y, I1248FN1249H, I1248YN1249H, I1248F/V1249W, I1248YN1249W, I1248H/ bind i V 1249W, I1248Y/V1249F, I1248H/V1249F, or I1248HN1249Y. Other substitution mutations are = = also disclosed. Isolated modified receptor binding domains, chimeric molecules, pharmaceutical _ total compositions, and methods of using the same are also disclosed. = ..... actin = = FIG. 4A 4 = — = 2 1 — Il Ir ... ' Il ei 4. 1' ‘., IN 4B FIG. P S I ei C [Continued on next page] WO 2017/214447 Al MIDEDIMOMMIDIRMEM001101011101110HOHNEVOIMIE 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 amendments (Rule 48.2(h)) of receipt of
SG11201810210UA 2016-06-08 2017-06-08 Engineered botulinum neurotoxins SG11201810210UA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662347579P 2016-06-08 2016-06-08
PCT/US2017/036628 WO2017214447A1 (en) 2016-06-08 2017-06-08 Engineered botulinum neurotoxins

Publications (1)

Publication Number Publication Date
SG11201810210UA true SG11201810210UA (en) 2018-12-28

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SG10201912099TA SG10201912099TA (en) 2016-06-08 2017-06-08 Engineered botulinum neurotoxins

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Country Status (13)

Country Link
US (1) US11104891B2 (en)
EP (1) EP3468985A1 (en)
JP (2) JP7152392B2 (en)
KR (1) KR20190025906A (en)
CN (1) CN109476713A (en)
AU (1) AU2017277905B2 (en)
BR (1) BR112018075363A2 (en)
CA (1) CA3026492A1 (en)
EA (1) EA201892784A1 (en)
IL (1) IL263058B2 (en)
MX (1) MX2018015254A (en)
SG (2) SG11201810210UA (en)
WO (1) WO2017214447A1 (en)

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EP3274364B1 (en) * 2015-03-26 2021-08-04 President and Fellows of Harvard College Engineered botulinum neurotoxin
TW201718627A (en) * 2015-06-11 2017-06-01 梅茲製藥有限兩合公司 Recombinant clostridial neurotoxin, a use thereof, and a method for generating the same, a pharmaceutical composition comprising the same and a precursor corresponding to the same, a nucleic acid sequence encoding the precursor and a method for obtaining
GB201607901D0 (en) * 2016-05-05 2016-06-22 Ipsen Biopharm Ltd Chimeric neurotoxins
UA127310C2 (en) * 2016-05-16 2023-07-19 Презідент Енд Феллоуз Оф Гарвард Колледж Method for purification and activation of botulinum neurotoxin
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US11117935B2 (en) 2016-08-24 2021-09-14 President And Fellows Of Harvard College Engineered botulinum neurotoxin
US11129906B1 (en) 2016-12-07 2021-09-28 David Gordon Bermudes Chimeric protein toxins for expression by therapeutic bacteria
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CN114957482A (en) * 2021-02-26 2022-08-30 重庆誉颜制药有限公司 Modified single-chain polypeptide of neurotoxin and application thereof
KR20230001254A (en) 2021-06-28 2023-01-04 (주)메디톡스 Recombinant botulinum toxin type A light chain, recombinant botulinum toxin, and its compositions, uses and methods
KR20230001260A (en) 2021-06-28 2023-01-04 (주)메디톡스 Recombinant botulinum toxin type A light chain, recombinant botulinum toxin, and its compositions, uses and methods
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CN114369623B (en) * 2022-01-12 2023-07-07 中国人民解放军空军军医大学 Syntagmin 2-RNAi based on Cre-lox recombination system and application thereof
CN114410683B (en) * 2022-01-12 2023-11-28 中国人民解放军空军军医大学 RIM3-RNAi based on Cre-lox recombination system and application thereof
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Also Published As

Publication number Publication date
WO2017214447A1 (en) 2017-12-14
AU2017277905B2 (en) 2022-04-14
JP7152392B2 (en) 2022-10-12
JP2019523015A (en) 2019-08-22
CN109476713A (en) 2019-03-15
CA3026492A1 (en) 2017-12-14
US20190300869A1 (en) 2019-10-03
AU2017277905A1 (en) 2018-12-20
US11104891B2 (en) 2021-08-31
IL263058A (en) 2018-12-31
EA201892784A1 (en) 2019-05-31
MX2018015254A (en) 2019-08-16
IL263058B2 (en) 2023-11-01
SG10201912099TA (en) 2020-02-27
IL263058B1 (en) 2023-07-01
BR112018075363A2 (en) 2019-03-19
KR20190025906A (en) 2019-03-12
EP3468985A1 (en) 2019-04-17
JP2022112031A (en) 2022-08-01

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