+

WO2009001743A1 - 新規adamts-13改変体 - Google Patents

新規adamts-13改変体 Download PDF

Info

Publication number
WO2009001743A1
WO2009001743A1 PCT/JP2008/061211 JP2008061211W WO2009001743A1 WO 2009001743 A1 WO2009001743 A1 WO 2009001743A1 JP 2008061211 W JP2008061211 W JP 2008061211W WO 2009001743 A1 WO2009001743 A1 WO 2009001743A1
Authority
WO
WIPO (PCT)
Prior art keywords
adamts
acid residue
residue
domain
aspartic acid
Prior art date
Application number
PCT/JP2008/061211
Other languages
English (en)
French (fr)
Inventor
Kenji Soejima
Original Assignee
Juridical Foundation The Chemo-Sero-Therapeutic Research Institute
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 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute filed Critical Juridical Foundation The Chemo-Sero-Therapeutic Research Institute
Priority to JP2009520528A priority Critical patent/JP5254973B2/ja
Priority to EP08777372.7A priority patent/EP2172544B1/en
Priority to US12/666,051 priority patent/US8685665B2/en
Publication of WO2009001743A1 publication Critical patent/WO2009001743A1/ja
Priority to US14/166,177 priority patent/US8906661B2/en
Priority to US14/527,856 priority patent/US9109217B2/en

Links

Classifications

    • 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)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489Metalloendopeptidases (3.4.24)
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • 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)
    • C12Y304/24087ADAMTS13 endopeptidase (3.4.24.87)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Urology & Nephrology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

 ADAMTS-13の酵素活性を増強させる方法及び/又は抗ADAMTS-13中和抗体との反応性を低減させる方法、並びに当該方法により作製されたADAMTS-13の改変体を提供する。本発明の方法は、ADAMTS-13のディスインテグリン様ドメイン、システインリッチドメイン又はスペーサードメインに存在する荷電アミノ酸のうち、下記アミノ酸を除く少なくとも一つを他のアミノ酸に置換することを特徴とする:ディスインテグリン様ドメイン内の第326位のアルギニン、第330位のアスパラギン酸、第343位のアスパラギン酸及び第349位のアルギニン、システインリッチドメイン内の第480位のアスパラギン酸、第488位のアルギニン、第498位のアルギニン、第507位のアルギニン、第533位のアスパラギン酸及び第543位のアスパラギン酸、並びにスペーサードメイン内の第641位のグルタミン酸及び第660位のアルギニン。当該方法により作製されたADAMTS-13の改変体を有効成分として含有する血栓性疾患の治療剤も提供される。
PCT/JP2008/061211 2007-06-22 2008-06-19 新規adamts-13改変体 WO2009001743A1 (ja)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2009520528A JP5254973B2 (ja) 2007-06-22 2008-06-19 新規adamts−13改変体
EP08777372.7A EP2172544B1 (en) 2007-06-22 2008-06-19 Novel adamts-13 mutant
US12/666,051 US8685665B2 (en) 2007-06-22 2008-06-19 ADAMTS-13 mutant
US14/166,177 US8906661B2 (en) 2007-06-22 2014-01-28 ADAMTS-13 mutant
US14/527,856 US9109217B2 (en) 2007-06-22 2014-10-30 ADAMTS-13 mutant

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP2007164531 2007-06-22
JP2007-164531 2007-06-22
JP2008-020177 2008-01-31
JP2008020177 2008-01-31
JP2008-020012 2008-01-31
JP2008020012 2008-01-31

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/666,051 A-371-Of-International US8685665B2 (en) 2007-06-22 2008-06-19 ADAMTS-13 mutant
US14/166,177 Division US8906661B2 (en) 2007-06-22 2014-01-28 ADAMTS-13 mutant

Publications (1)

Publication Number Publication Date
WO2009001743A1 true WO2009001743A1 (ja) 2008-12-31

Family

ID=40185561

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2008/061211 WO2009001743A1 (ja) 2007-06-22 2008-06-19 新規adamts-13改変体

Country Status (4)

Country Link
US (3) US8685665B2 (ja)
EP (3) EP2759593B1 (ja)
JP (2) JP5254973B2 (ja)
WO (1) WO2009001743A1 (ja)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013500711A (ja) * 2009-07-31 2013-01-10 バクスター・ヘルスケヤー・ソシエテ・アノニム 組換えadamts13および他のタンパク質を精製する方法ならびにそれらの組成物
WO2013096793A1 (en) * 2011-12-21 2013-06-27 The Children's Hospital Of Philadelphia Gain-of-function adamts13 variants resistant to autoantibody inhibition and methods of use thereof
WO2023235964A1 (en) * 2022-06-06 2023-12-14 Mcmaster University Thrombolytic protease resistant adamts13 mutants

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2759593B1 (en) * 2007-06-22 2017-03-01 The Chemo-Sero-Therapeutic Research Institute Novel ADAMTS-13 mutant
GB201510870D0 (en) * 2015-05-26 2015-08-05 Baxalta Inc And Katholieke Universiteit Leuven And Baxalta Gmbh Treatment of infarction
IL300596A (en) * 2020-08-13 2023-04-01 Hadasit Medical Res Services & Development Limited Mutants of disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (adamts-13), preparations and their uses in therapeutic methods
JP2023549878A (ja) 2020-11-18 2023-11-29 グリーン・クロス・コーポレイション 自己抗体に対する回避率又は活性が向上したadamts13バリアント
KR20230159285A (ko) * 2022-05-10 2023-11-21 주식회사 녹십자 혈장 단백질의 동결 건조를 위한 신규한 액상 제형물
TW202400238A (zh) * 2022-05-10 2024-01-01 南韓商綠十字股份有限公司 血漿蛋白之新穎液體調配物

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2824434B2 (ja) 1989-11-28 1998-11-11 財団法人化学及血清療法研究所 新規発現ベクター
WO2002088366A1 (fr) 2001-04-25 2002-11-07 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Enzyme de clivage du facteur de von willebrand (vwf)
WO2004029242A1 (ja) 2002-09-25 2004-04-08 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute フォンビルブランド因子特異的切断酵素に対する抗体及びそれを用いたアッセイ系
WO2005062054A1 (ja) 2003-12-22 2005-07-07 Mitsubishi Kagaku Iatron, Inc. フォンヴィルブランド因子分解酵素の測定による血栓症の検出方法
JP2007248395A (ja) 2006-03-17 2007-09-27 Chemo Sero Therapeut Res Inst 急性冠症候群でのadamts13の測定と利用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7037658B2 (en) * 2001-08-16 2006-05-02 Regents Of University Of Michigan Methods and compositions for detecting variant ADAMTS13 genes
US7572591B2 (en) * 2003-03-17 2009-08-11 The Juridical Foundation Chemo-Sero-Therapeutic Research Institute Construct comprising recognition domain of antibody against von Willebrand factor-specific cleaving enzyme
EP2759593B1 (en) * 2007-06-22 2017-03-01 The Chemo-Sero-Therapeutic Research Institute Novel ADAMTS-13 mutant

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2824434B2 (ja) 1989-11-28 1998-11-11 財団法人化学及血清療法研究所 新規発現ベクター
WO2002088366A1 (fr) 2001-04-25 2002-11-07 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Enzyme de clivage du facteur de von willebrand (vwf)
WO2004029242A1 (ja) 2002-09-25 2004-04-08 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute フォンビルブランド因子特異的切断酵素に対する抗体及びそれを用いたアッセイ系
WO2005062054A1 (ja) 2003-12-22 2005-07-07 Mitsubishi Kagaku Iatron, Inc. フォンヴィルブランド因子分解酵素の測定による血栓症の検出方法
JP2007248395A (ja) 2006-03-17 2007-09-27 Chemo Sero Therapeut Res Inst 急性冠症候群でのadamts13の測定と利用

Non-Patent Citations (22)

* Cited by examiner, † Cited by third party
Title
"ANTIBODY ENGINEERING"
"BIOINFORMl\TICS A Practical Guide to the Analysis of Genes and Proteins", JOHN WILEY & SONS, INC.
"Molecular Cloning", vol. 3, 2001, COLD SPRING HARBOR LABORATORY PRESS
ANDERSON, P.J.; KOKAME, K.; SADLER, J.E.: "Zinc and calcium ions cooperatively modulate ADAMTS13 activity", J. BIOL. CHEM., vol. 281, 2006, pages 850 - 857, XP002660108, DOI: doi:10.1074/JBC.M504540200
BERNARDO, A.; BALL, C.; NOLASCO, L.; MOAKE, J.F.; DONG, J.F.: "Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow", BLOOD, vol. 104, 2004, pages 100 - 106
BRIAN K. KAY ET AL.: "Antibody Engineering: A PRACTICAL APPROACH"
DATABASE GENBANK [online] XP008138836, accession no. NCBI Database accession no. (DQ422807) *
GERRITSEN, HE.; TURECEK, PL.; SCHWARZ, HP.; LAMMLE, B.; FURLAN, M.: "Assay of von Willebrand factor (vWF)-cleaving protease based on decreased collagen binding affinity of degraded vWF: a tool for the diagnosis of thrombotic thrombocytopenic purpura (TTP). Thromb", HAEMOST., vol. 82, 1999, pages 1386 - 1389, XP000922765
ISONISHI A. ET AL.: "Ko ADAMTS13 Mouse Monoclonal Kotai no Sakusei to Sono Seijo", JAPANESE JOURNAL OF THROMBOSIS AND HEMOSTASIS, vol. 15, no. 5, 2004, pages 422 + LECTURE NO. O-07, XP008129123 *
KOKAME K. ET AL.: "von Willebrand Inshi Setsudan Koso o Cord suru Hito ADAMTS13 Idenshi no Hen'i to Tagata", SEIKAGAKU, vol. 74, no. 8, 2002, pages 1040 + LECTURE NO. 4P-460, XP008129122 *
KOZAK M, J. MOL. BIOL., vol. 196, 1987, pages 947
MILSTEIN ET AL., METHOD ENZYMOL., vol. 73, 1981, pages 3 - 46
MORRISON K.L. ET AL.: "Combinatorial alanine-scanning", CURRENT OPINION IN CHEMICAL BIOLOGY, vol. 5, no. 3, 2001, pages 302 - 307, XP002325957 *
NOLASCO, L.H.; TURNER, N.A.; BERNARDO, A.; TAO, Z.; CLEARY, T.G.; DONG, J.F.; MOAKE, J.L.: "emolytic uremic syndrome-associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers", BLOOD, vol. 106, 2005, pages 4199 - 4209
ONO, T.; MIMURO, J.; MADOIWA, S.; SOEJ IMA, K.; KASHIWAKURA, Y.; ISHIWATA, A.; TAKANO, K.; OHMORI, T.; SAKATA, Y.: "Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure", BLOOD, vol. 107, 2006, pages 528 - 534, XP003008274, DOI: doi:10.1182/blood-2005-03-1087
PLAIMAUER B. ET AL.: "Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation", BLOOD, vol. 107, no. 1, 2006, pages 118 - 125, XP008129136 *
See also references of EP2172544A4 *
SOEJ IMA, K.; NAKAMURA, H.; HIRASHIMA, M.; MORIKAWA, W.; NOZAKI, C.; NAKAGAKI, T.: "Analysis on the molecular species and concentration of circulating ADAMTS13 in blood", BIOCHEM., vol. 139, 2006, pages 147 - 154, XP002380916, DOI: doi:10.1093/jb/mvj013
SOEJIMA K. ET AL.: "VWF Setsudan Koso (ADAMTS13) no Kozo to Kino", IGAKU NO AYUMI, KETSUEKI SHIKKAN -STATE OF ARTS VER 3, 2005, pages 143 - 146 *
SOEJIMA, K.; MATSUMOTO, M.; KOKAME, K.; YAGI, H.; ISHIZASHI, H.; MAEDA, H., NOZAKI, C.; MIYATA, T.; FUJIMURA, Y.; NAKAGAKI, T.: "ADAMTS-13 cysteine- rich/spacer domains are functionally essential for von Willebrand factor cleavage", BLOOD, vol. 102, 2003, pages 3232 - 3237, XP002340971, DOI: doi:10.1182/blood-2003-03-0908
SOEJIMA, K.; MIMURA, N.; HIRASHIMA, M.; MAEDA, H.; HAMAMOTO, T.; NAKAGAKI, T.; NOZAKI, C.: "A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving, protease?", J. BIOCHEM., vol. 130, 2001, pages 475 - 480, XP001079224
SOEJIMA, K.; NAKAGAKI, T.: "Interplay between ADAMTS13 and von Willebrand factor in inherited and acquired thrombotic microangiopathies", SEMIN. HEMATOL., vol. 42, 2005, pages 56 - 62

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013500711A (ja) * 2009-07-31 2013-01-10 バクスター・ヘルスケヤー・ソシエテ・アノニム 組換えadamts13および他のタンパク質を精製する方法ならびにそれらの組成物
JP2015147815A (ja) * 2009-07-31 2015-08-20 バクスター・ヘルスケヤー・ソシエテ・アノニムBaxter Healthcare SA 組換えadamts13および他のタンパク質を精製する方法ならびにそれらの組成物
WO2013096793A1 (en) * 2011-12-21 2013-06-27 The Children's Hospital Of Philadelphia Gain-of-function adamts13 variants resistant to autoantibody inhibition and methods of use thereof
US20150044171A1 (en) * 2011-12-21 2015-02-12 The Children's Hospital Of Philadelphia Gain-of-Function ADAMTS13 Variants Resistant to Auto Antibody Inhibition and Methods of Use Thereof
US9546360B2 (en) * 2011-12-21 2017-01-17 The Children's Hospital Of Philadelphia Gain-of-function ADAMTS13 variants resistant to auto antibody inhibition and methods of use thereof
WO2023235964A1 (en) * 2022-06-06 2023-12-14 Mcmaster University Thrombolytic protease resistant adamts13 mutants

Also Published As

Publication number Publication date
US8906661B2 (en) 2014-12-09
US20120064057A1 (en) 2012-03-15
EP2374878A3 (en) 2012-05-30
EP2172544A4 (en) 2010-09-22
JPWO2009001743A1 (ja) 2010-08-26
EP2374878A2 (en) 2011-10-12
JP5254973B2 (ja) 2013-08-07
US9109217B2 (en) 2015-08-18
US20140193881A1 (en) 2014-07-10
EP2374878B1 (en) 2015-08-19
EP2172544A1 (en) 2010-04-07
EP2759593B1 (en) 2017-03-01
JP2013116126A (ja) 2013-06-13
JP5492322B2 (ja) 2014-05-14
EP2172544B1 (en) 2014-11-12
US8685665B2 (en) 2014-04-01
EP2759593A1 (en) 2014-07-30
US20150050716A1 (en) 2015-02-19

Similar Documents

Publication Publication Date Title
WO2009001743A1 (ja) 新規adamts-13改変体
WO2006116949A8 (fr) Nouvelle souche du bacillus subtilis et son utilisation dans la préparation de médicament pour traiter la thrombose
BRPI0509671A (pt) alfa-amilases mutante
EP3892709A3 (en) Variants and compositions comprising variants with high stability in presence of a chelating agent
MX2010006096A (es) Anticuerpo anti-nr10 y su uso.
MX2007013725A (es) Produccion de beta-glucanos y mananos.
MXPA06010900A (es) Inhibidores de histona desacetilasa.
MY155049A (en) Immuno-based botolinum toxin serotype a activity assay
MX2009005655A (es) Composiciones y usos de un polipeptido alfa-amilasa del bacilo de la especie 195.
MY151457A (en) Topical formulation and uses thereof
HK1131167A1 (zh) 淚液脂質運載蛋白的突變蛋白及其獲得方法
WO2010020475A3 (de) Verfahren zur verbesserung der reinigungsleistung eines wasch- oder reinigungsmittels
WO2006093348A3 (en) Method and composition for treating peripheral vascular diseases
TW200745047A (en) Heterocyclic compounds
WO2007117482A3 (en) Renin inhibitors
WO2008024139A3 (en) Inhibitors of fatty acid amide hydrolase
WO2006022664A3 (en) Alanine 2, 3 aminomutases
MY159035A (en) Control agent for soft rot and control method for the same
MX2009003763A (es) Inhibidores de metaloproteasa derivados de heterociclicos.
WO2007079180A3 (en) Inhibitors of fatty acid amide hydrolase
WO2013026575A3 (en) Glucose oxidase
WO2009019138A3 (en) Enzymatic process for obtaining 17 alpha-monoesters of cortexolone and/or its 9,11-dehydroderivatives
PT1851322E (pt) Processo para a redução enzimática enantiosselectiva de compostos cetónicos
SI1656450T1 (sl) Cefalosporin-C-acilazni mutant in postopek za pripravo 7-ACA z uporabo le-tega
WO2006063055A3 (en) Enzyme conjugates for use as detoxifying agents

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08777372

Country of ref document: EP

Kind code of ref document: A1

DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2009520528

Country of ref document: JP

Ref document number: 12666051

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2008777372

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务,不要输入任何密码和下载