WO2009042962A3 - Antidotes for factor xa inhibitors and methods of using the same - Google Patents

Antidotes for factor xa inhibitors and methods of using the same Download PDF

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Publication number
WO2009042962A3
WO2009042962A3 PCT/US2008/078014 US2008078014W WO2009042962A3 WO 2009042962 A3 WO2009042962 A3 WO 2009042962A3 US 2008078014 W US2008078014 W US 2008078014W WO 2009042962 A3 WO2009042962 A3 WO 2009042962A3
Authority
WO
WIPO (PCT)
Prior art keywords
factor
antidotes
inhibitors
methods
same
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2008/078014
Other languages
French (fr)
Other versions
WO2009042962A9 (en
WO2009042962A2 (en
Inventor
Genmin Lu
David R Phillips
Patrick Andre
Uma Sinha
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Portola Pharmaceuticals LLC
Original Assignee
Portola Pharmaceuticals LLC
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
Priority to MX2010003095A priority Critical patent/MX2010003095A/en
Priority to ES08834136.7T priority patent/ES2597436T3/en
Priority to NZ583944A priority patent/NZ583944A/en
Priority to BR122022001846-7A priority patent/BR122022001846B1/en
Priority to EP14197779.3A priority patent/EP2915564B1/en
Priority to SI200831678A priority patent/SI2193196T1/en
Priority to BRPI0816837-7A priority patent/BRPI0816837B1/en
Priority to HRP20161255TT priority patent/HRP20161255T1/en
Priority to KR1020167003860A priority patent/KR102069498B1/en
Priority to KR1020177023761A priority patent/KR20170100071A/en
Priority to AU2008304192A priority patent/AU2008304192B9/en
Priority to KR1020207001549A priority patent/KR102271404B1/en
Priority to EP20198287.3A priority patent/EP3824902A1/en
Priority to LTEP08834136.7T priority patent/LT2193196T/en
Priority to EP08834136.7A priority patent/EP2193196B1/en
Priority to KR1020107008718A priority patent/KR101698214B1/en
Priority to JP2010527220A priority patent/JP5637561B2/en
Priority to PL14197779T priority patent/PL2915564T3/en
Priority to CN2008801079738A priority patent/CN101802188B/en
Priority to EP16167534.3A priority patent/EP3078743B1/en
Priority to CA2697583A priority patent/CA2697583C/en
Priority to DK08834136.7T priority patent/DK2193196T3/en
Priority to PL16167534T priority patent/PL3078743T3/en
Application filed by Portola Pharmaceuticals LLC filed Critical Portola Pharmaceuticals LLC
Publication of WO2009042962A2 publication Critical patent/WO2009042962A2/en
Publication of WO2009042962A3 publication Critical patent/WO2009042962A3/en
Publication of WO2009042962A9 publication Critical patent/WO2009042962A9/en
Priority to IL203993A priority patent/IL203993A/en
Priority to ZA2010/02039A priority patent/ZA201002039B/en
Anticipated expiration legal-status Critical
Priority to AU2013205326A priority patent/AU2013205326A1/en
Priority to CY20161101020T priority patent/CY1118482T1/en
Priority to AU2017200212A priority patent/AU2017200212A1/en
Priority to IL255397A priority patent/IL255397B/en
Priority to IL264886A priority patent/IL264886B/en
Priority to AU2019204123A priority patent/AU2019204123A1/en
Priority to NO2019040C priority patent/NO2019040I1/en
Priority to IL272926A priority patent/IL272926A/en
Priority to CY20201100715T priority patent/CY1123504T1/en
Priority to NL301063C priority patent/NL301063I2/en
Priority to FR20C1045C priority patent/FR20C1045I2/en
Priority to NO2020033C priority patent/NO2020033I1/en
Priority to CY2020042C priority patent/CY2020042I2/en
Priority to LTPA2020540C priority patent/LTC3078743I2/en
Priority to AU2021218033A priority patent/AU2021218033A1/en
Priority to AU2024287094A priority patent/AU2024287094A1/en
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/4826—Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/4833—Thrombin (3.4.21.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/482—Serine endopeptidases (3.4.21)
    • A61K38/4853—Kallikrein (3.4.21.34 or 3.4.21.35)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • 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
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6432—Coagulation factor Xa (3.4.21.6)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21006—Coagulation factor Xa (3.4.21.6)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Toxicology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.
PCT/US2008/078014 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same Ceased WO2009042962A2 (en)

Priority Applications (41)

Application Number Priority Date Filing Date Title
PL16167534T PL3078743T3 (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
NZ583944A NZ583944A (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
BR122022001846-7A BR122022001846B1 (en) 2007-09-28 2008-09-26 USE OF TWO-CHAIN POLYPEPTIDE FOR DRUG PREPARATION TO REDUCE BLEEDING
EP14197779.3A EP2915564B1 (en) 2007-09-28 2008-09-26 Antidotes for factor XA inhibitors and methods of using the same
SI200831678A SI2193196T1 (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
BRPI0816837-7A BRPI0816837B1 (en) 2007-09-28 2008-09-26 PHARMACEUTICAL COMPOSITIONS, ISOLATED TWO-CHAIN POLYPEPTIDE AND USE OF A PHARMACEUTICAL COMPOSITION
HRP20161255TT HRP20161255T1 (en) 2007-09-28 2008-09-26 ANTI-DOTS FOR XA FACTOR INHIBITORS AND PROCEDURES FOR THEIR USE
KR1020167003860A KR102069498B1 (en) 2007-09-28 2008-09-26 ANTIDOTES FOR FACTOR Xa INHIBITORS AND METHODS OF USING THE SAME
KR1020177023761A KR20170100071A (en) 2007-09-28 2008-09-26 ANTIDOTES FOR FACTOR Xa INHIBITORS AND METHODS OF USING THE SAME
AU2008304192A AU2008304192B9 (en) 2007-09-28 2008-09-26 Antidotes for factor Xa inhibitors and methods of using the same
KR1020207001549A KR102271404B1 (en) 2007-09-28 2008-09-26 ANTIDOTES FOR FACTOR Xa INHIBITORS AND METHODS OF USING THE SAME
ES08834136.7T ES2597436T3 (en) 2007-09-28 2008-09-26 Antidotes for factor Xa inhibitors and procedures for their use
LTEP08834136.7T LT2193196T (en) 2007-09-28 2008-09-26 ANTIDOTES FOR FACTOR Xa INHIBITORS AND METHODS OF USING THE SAME
EP08834136.7A EP2193196B1 (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
KR1020107008718A KR101698214B1 (en) 2007-09-28 2008-09-26 ANTIDOTES FOR FACTOR Xa INHIBITORS AND METHODS OF USING THE SAME
JP2010527220A JP5637561B2 (en) 2007-09-28 2008-09-26 Antidote to factor Xa inhibitor and method of use thereof
PL14197779T PL2915564T3 (en) 2007-09-28 2008-09-26 Antidotes for factor XA inhibitors and methods of using the same
CN2008801079738A CN101802188B (en) 2007-09-28 2008-09-26 Antidotes for factor Xa inhibitors and methods of use thereof
EP16167534.3A EP3078743B1 (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
CA2697583A CA2697583C (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
DK08834136.7T DK2193196T3 (en) 2007-09-28 2008-09-26 Clinical profile of Factor Xa inhibitors, and methods of use thereof
MX2010003095A MX2010003095A (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same.
EP20198287.3A EP3824902A1 (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same
IL203993A IL203993A (en) 2007-09-28 2010-02-16 Antidotes for factor xa inhibitors and methods of using the same
ZA2010/02039A ZA201002039B (en) 2007-09-28 2010-03-23 Antidotes for factor xa inhibitors and methods of using the same
AU2013205326A AU2013205326A1 (en) 2007-09-28 2013-04-11 Antidotes for factor XA inhibitors and methods of using the same
CY20161101020T CY1118482T1 (en) 2007-09-28 2016-10-12 CONDITIONS FOR THEIR SUSPENSIONS AND METHODS FOR USE
AU2017200212A AU2017200212A1 (en) 2007-09-28 2017-01-12 Antidotes for factor XA inhibitors and methods of using the same
IL255397A IL255397B (en) 2007-09-28 2017-11-02 Antidotes for factor xa inhibitors and methods of using the same
IL264886A IL264886B (en) 2007-09-28 2019-02-18 Antidotes for factor xa inhibitors and methods of using the same
AU2019204123A AU2019204123A1 (en) 2007-09-28 2019-06-13 Antidotes for factor XA inhibitors and methods of using the same
NO2019040C NO2019040I1 (en) 2007-09-28 2019-11-08 andexane alpha
IL272926A IL272926A (en) 2007-09-28 2020-02-26 Antidotes for factor xa inhibitors and methods of using the same
CY20201100715T CY1123504T1 (en) 2007-09-28 2020-08-04 ANTIDOTES FOR FACTOR HA INHIBITORS AND METHODS OF USING THEM
NL301063C NL301063I2 (en) 2007-09-28 2020-09-09 Andexanet alpha
NO2020033C NO2020033I1 (en) 2007-09-28 2020-09-23 andexane alpha
FR20C1045C FR20C1045I2 (en) 2007-09-28 2020-09-23 ANTIDOTES FOR FACTOR XA INHIBITORS AND METHODS OF USE THEREOF
CY2020042C CY2020042I2 (en) 2007-09-28 2020-12-16 ANTIDOTES FOR FACTOR HA INHIBITORS AND METHODS OF USING THEM
LTPA2020540C LTC3078743I2 (en) 2007-09-28 2020-12-22 ANTIBODIES TO FACTOR XA INHIBITORS AND THEIR USE
AU2021218033A AU2021218033A1 (en) 2007-09-28 2021-08-17 Antidotes for factor XA inhibitors and methods of using the same
AU2024287094A AU2024287094A1 (en) 2007-09-28 2024-12-20 Antidotes for factor XA inhibitors and methods of using the same

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US97634307P 2007-09-28 2007-09-28
US60/976,343 2007-09-28
US9057408P 2008-08-20 2008-08-20
US61/090,574 2008-08-20

Publications (3)

Publication Number Publication Date
WO2009042962A2 WO2009042962A2 (en) 2009-04-02
WO2009042962A3 true WO2009042962A3 (en) 2009-06-04
WO2009042962A9 WO2009042962A9 (en) 2009-09-11

Family

ID=40481812

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/078014 Ceased WO2009042962A2 (en) 2007-09-28 2008-09-26 Antidotes for factor xa inhibitors and methods of using the same

Country Status (26)

Country Link
US (8) US8153590B2 (en)
EP (4) EP3824902A1 (en)
JP (7) JP5637561B2 (en)
KR (4) KR102069498B1 (en)
CN (4) CN102559644B (en)
AU (7) AU2008304192B9 (en)
BR (2) BRPI0816837B1 (en)
CA (1) CA2697583C (en)
CY (3) CY1118482T1 (en)
DK (3) DK2193196T3 (en)
ES (3) ES2597436T3 (en)
FR (1) FR20C1045I2 (en)
HR (2) HRP20161255T1 (en)
HU (4) HUE050063T2 (en)
IL (4) IL203993A (en)
LT (3) LT2193196T (en)
MX (1) MX2010003095A (en)
NL (1) NL301063I2 (en)
NO (2) NO2019040I1 (en)
NZ (1) NZ583944A (en)
PL (3) PL3078743T3 (en)
PT (3) PT3078743T (en)
SG (1) SG185263A1 (en)
SI (3) SI3078743T1 (en)
WO (1) WO2009042962A2 (en)
ZA (2) ZA201002039B (en)

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US7696352B2 (en) * 2004-06-18 2010-04-13 Millennium Pharmaceuticals, Inc. Factor Xa inhibitors
EP2016072B1 (en) 2006-05-05 2014-07-16 Millennium Pharmaceuticals, Inc. Factor xa inhibitors
KR102069498B1 (en) 2007-09-28 2020-01-23 포톨라 파마슈티컬스, 인코포레이티드 ANTIDOTES FOR FACTOR Xa INHIBITORS AND METHODS OF USING THE SAME
CA2743496C (en) 2008-11-14 2018-03-27 Portola Pharmaceuticals, Inc. Antidotes for factor xa inhibitors and methods of using the same in combination with blood coagulating agents
EP2379096B1 (en) * 2008-12-19 2019-10-30 Baxalta GmbH Tfpi inhibitors and methods of use
PL3604510T3 (en) * 2009-03-30 2025-07-28 Alexion Pharmaceuticals, Inc. Antidotes for factor xa inhibitors and methods of using the same
EP2453910B1 (en) 2009-07-15 2016-08-31 Portola Pharmaceuticals, Inc. Unit dose formulation of antidote for factor xa inhibitors for use in preventing bleeding
GB0916576D0 (en) * 2009-09-22 2009-10-28 Malmsten Nils M Polypeptides and uses thereof
EP2316931B1 (en) 2009-10-30 2016-12-28 Senova Gesellschaft für Biowissenschaft und Technik mbH Polymer-coupled peptidases
US8742120B2 (en) * 2009-12-17 2014-06-03 Millennium Pharmaceuticals, Inc. Methods of preparing factor xa inhibitors and salts thereof
EP2513094B1 (en) * 2009-12-17 2015-12-16 Millennium Pharmaceuticals, Inc. Crystalline salts of a factor xa inhibitor
TWI513466B (en) 2010-01-20 2015-12-21 Boehringer Ingelheim Int Anticoagulant antidotes
ES2983470T3 (en) 2010-03-19 2024-10-23 Takeda Pharmaceuticals Co TFPI inhibitors and methods of use
TW201221128A (en) 2010-09-01 2012-06-01 Portola Pharm Inc Crystalline forms of a factor Xa inhibitor
AR082803A1 (en) * 2010-09-01 2013-01-09 Portola Pharm Inc METHODS AND FORMULATIONS FOR THE TREATMENT OF THROMBOSIS WITH BETRIXABAN AND A GLICOPROTEIN P INHIBITOR
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CA2697583A1 (en) 2009-04-02
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