WO2007015107A2 - Artificial platelets - Google Patents

Artificial platelets Download PDF

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Publication number
WO2007015107A2
WO2007015107A2 PCT/GB2006/002934 GB2006002934W WO2007015107A2 WO 2007015107 A2 WO2007015107 A2 WO 2007015107A2 GB 2006002934 W GB2006002934 W GB 2006002934W WO 2007015107 A2 WO2007015107 A2 WO 2007015107A2
Authority
WO
WIPO (PCT)
Prior art keywords
peptide
fibrinogen
fibrinogen binding
precursor
wound site
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/GB2006/002934
Other languages
English (en)
French (fr)
Other versions
WO2007015107A3 (en
Inventor
Alison Helena Goodall
Sarah Margaret Taylor
Greg Francis Walker
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.)
Haemostatix Ltd
Original Assignee
Haemostatix Ltd
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 Haemostatix Ltd filed Critical Haemostatix Ltd
Priority to CA002625917A priority Critical patent/CA2625917A1/en
Priority to AU2006274685A priority patent/AU2006274685A1/en
Priority to US11/997,540 priority patent/US20090203619A1/en
Priority to EP06765236.2A priority patent/EP1919508B1/en
Priority to JP2008524591A priority patent/JP2009505964A/ja
Publication of WO2007015107A2 publication Critical patent/WO2007015107A2/en
Publication of WO2007015107A3 publication Critical patent/WO2007015107A3/en
Priority to IL189105A priority patent/IL189105A0/en
Anticipated expiration legal-status Critical
Priority to US13/408,897 priority patent/US20130029913A1/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • 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
    • 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
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/14—Peptides being immobilised on, or in, an inorganic carrier
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids

Definitions

  • This invention relates to agents suitable for use as artificial platelets.
  • the agents may be used to treat patients with deficiencies in their own platelets, such as hereditary or acquired defects of platelet numbers (thrombocytopenia) or function (thrombasthenia).
  • Platelet transfusion is currently the only effective treatment for acute bleeding and the prevention of bleeding in patients with disorders of platelet production and/or function.
  • shelf-life of platelet concentrates used for transfusion is only five days.
  • Product 1 is a peptide of sequence NH 2 -GPRPGGGGGGC (SEQ ID NO: 1) cross-linked through the terminal cysteine to a human albumin microsphere. Fibrinogen is bound to the peptide.
  • Product 2 is identical to Product 1 except that fibrinogen is not bound to the peptide. When administered, Product 2 binds endogenous fibrinogen via the peptide.
  • the peptide is capable of binding to fibrinogen such that fibrinogen is maintained in, or close to, its native conformation. This allows preferential interaction with the activated form of the GPIIb-IIIa receptor.
  • an agent for use as an artificial platelet comprising a fibrinogen binding precursor bound to an insoluble carrier, wherein the fibrinogen binding precursor can be converted by a wound site specific agent to a fibrinogen binding component bound to the carrier, the fibrinogen binding component having increased ability to bind fibrinogen compared to the fibrinogen binding precursor, and the fibrinogen binding precursor not being fibrinogen.
  • DVT pulmonary embolism
  • PE pulmonary embolism
  • the dissociation constant of the fibrinogen binding precursor for fibrinogen is greater than 1x10 "6 M.
  • the fibrinogen binding precursor may be a peptide or a peptide analogue, but is preferably a peptide.
  • the fibrinogen binding precursor comprises a fibrinogen binding peptide (i.e. the fibrinogen binding component) joined at its amino terminal end to a blocking component (preferably a peptide) that blocks or inhibits (i.e. reduces) binding of fibrinogen to the fibrinogen binding peptide. Cleavage of the fibrinogen binding precursor by the wound site specific agent exposes the fibrinogen binding peptide bound to the insoluble carrier.
  • the blocking component blocks or inhibits the ability of the fibrinogen binding peptide to bind fibrinogen until cleavage occurs.
  • the blocking component is a peptide of 1-30 amino acid residues in length.
  • the peptide may be capable of binding to the carboxy- and/or amino- terminal domain of the ⁇ -chain of fibrinogen.
  • the peptide may be capable of binding to an RGD-containing motif in one or both of these domains
  • the fibrinogen binding peptide may comprise a sequence derived from a fibrinogen-binding region of GPIIb or GPIIIa.
  • the peptide may comprise the sequence AVTDVNGDGRHDLLVGAPLYM (SEQ ID NO: 5) which corresponds to the sequence of amino acid residues 294-314 of GPIIb, or a fragment or derivative thereof that retains fibrinogen binding activity. Fragments known to retain fibrinogen binding activity are TDVNGDGRHDL (296-306) (SEQ ID NO: 6), GDGRHDLLVGAPL (300-312) (SEQ ID NO: 7), and GAPL (SEQ ID NO: 8).
  • the wound site targeting component may be immobilised to the insoluble carrier, bound to the fibrinogen binding precursor, or part of the fibrinogen binding precursor. In one embodiment the wound site targeting component and the fibrinogen binding precursor are cross-linked separately to the insoluble carrier.
  • the insoluble carrier may be a microparticle (including a solid, hollow, or porous microparticle), preferably a substantially spherical microparticle.
  • the microparticle may be formed of any suitable substance, for example cross-linked protein.
  • a suitable protein is albumin (serum-derived or recombinant, human or non human).
  • Microparticles suitable for use as insoluble carriers in the present invention may be formed by spray drying human serum albumin using well known spray drying technology, for example as in WO 92/18164.
  • a spacer will be required between the fibrinogen binding component and the insoluble carrier to ensure that the fibrinogen-binding activity of the fibrinogen binding component is not adversely affected by the insoluble carrier.
  • the surface of the insoluble carrier may sterically hinder binding of fibrinogen to the fibrinogen binding component unless this is a sufficient distance from the surface of the insoluble carrier.
  • the fibrinogen binding precursor is a peptide which comprises a fibrinogen binding peptide, and the precursor is bound to the insoluble carrier by a terminal amino acid residue
  • a spacer sequence is preferably present between the terminal amino acid residue and the fibrinogen binding peptide of the precursor.
  • the spacer sequence may, for example, be from 1-20, preferably 5- 20, amino acid residues in length.
  • the spacer sequence GGGGGG (SEQ ID NO: 29) or GGGGG (SEQ ID NO: 30) is preferred.
  • Spacer 3 NH 2 -GGGGGG-COOH (SEQ ID NO: 29).
  • microparticles were resuspended in 2.5ml 0.02M Tris containing 2 % mannitol pH 7.5. The microparticles were filled into 200 ⁇ l aliquots and stored at - 7O 0 C
  • a bleeding time of about 20 minutes is typical.
  • Agents of the invention should generally be able to reduce the bleeding time to less than 10 minutes in a minimum of three, and preferably all six, of the test rabbits in a group of six.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Inorganic Chemistry (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
PCT/GB2006/002934 2005-08-04 2006-08-04 Artificial platelets Ceased WO2007015107A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
CA002625917A CA2625917A1 (en) 2005-08-04 2006-08-04 Artificial platelets
AU2006274685A AU2006274685A1 (en) 2005-08-04 2006-08-04 Artificial platelets
US11/997,540 US20090203619A1 (en) 2005-08-04 2006-08-04 Artificial platelets
EP06765236.2A EP1919508B1 (en) 2005-08-04 2006-08-04 Artificial platelets
JP2008524591A JP2009505964A (ja) 2005-08-04 2006-08-04 人工血小板
IL189105A IL189105A0 (en) 2005-08-04 2008-01-29 Artificial platelets
US13/408,897 US20130029913A1 (en) 2005-08-04 2012-02-29 Artificial platelets

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0516091.6 2005-08-04
GBGB0516091.6A GB0516091D0 (en) 2005-08-04 2005-08-04 Therapeutic agent

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US13/408,897 Continuation US20130029913A1 (en) 2005-08-04 2012-02-29 Artificial platelets

Publications (2)

Publication Number Publication Date
WO2007015107A2 true WO2007015107A2 (en) 2007-02-08
WO2007015107A3 WO2007015107A3 (en) 2007-07-26

Family

ID=34984119

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2006/002934 Ceased WO2007015107A2 (en) 2005-08-04 2006-08-04 Artificial platelets

Country Status (9)

Country Link
US (2) US20090203619A1 (enExample)
EP (2) EP2335737A3 (enExample)
JP (1) JP2009505964A (enExample)
CN (1) CN101267843A (enExample)
AU (1) AU2006274685A1 (enExample)
CA (1) CA2625917A1 (enExample)
GB (2) GB0516091D0 (enExample)
IL (1) IL189105A0 (enExample)
WO (1) WO2007015107A2 (enExample)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008113796A1 (en) * 2007-03-21 2008-09-25 Dsm Ip Assets B.V. Cholesterol lowering protein hydrolysates
WO2009046843A1 (en) * 2007-09-11 2009-04-16 Mondobiotech Laboratories Ag Therapeutic uses of peptides kvlpvpq and/or tdvngdgrhdl
WO2009046844A1 (en) * 2007-09-11 2009-04-16 Mondobiotech Laboratories Ag Therapeutic uses of peptide tdvngdgrhdl
WO2008065388A3 (en) * 2006-11-27 2009-11-26 Haemostatix Limited Biogel
WO2012104638A1 (en) 2011-02-01 2012-08-09 Haemostatix Limited Therapeutic agents with improved fibrinogen binding
WO2013021353A1 (en) * 2011-08-11 2013-02-14 Bar-Ilan University Surface modified proteinaceous spherical particles and uses thereof
WO2013114132A1 (en) * 2012-02-01 2013-08-08 Haemostatix Limited Haemostatic wound dressing
WO2014197816A1 (en) * 2013-06-06 2014-12-11 Massachusetts Institute Of Technology Stimulus responsive nanocomplexes and methods of use thereof
WO2015104544A1 (en) * 2014-01-08 2015-07-16 Haemostatix Limited Peptide dendrimers comprising fibrinogen-binding peptides
US11192936B2 (en) 2014-01-10 2021-12-07 Bioverativ Therapeutics Inc. Factor VIII chimeric proteins and uses thereof
US12030925B2 (en) 2018-05-18 2024-07-09 Bioverativ Therapeutics Inc. Methods of treating hemophilia A
US12161696B2 (en) 2016-12-02 2024-12-10 Bioverativ Therapeutics Inc. Methods of treating hemophilic arthropathy using chimeric clotting factors

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WO2014210558A1 (en) * 2013-06-28 2014-12-31 Biogen Idec Ma Inc. Thrombin cleavable linker with xten and its uses thereof
WO2015073418A2 (en) * 2013-11-15 2015-05-21 President And Fellows Of Harvard College Methods and assays for factor viii activity
GB201508024D0 (en) * 2015-05-11 2015-06-24 Haemostatix Ltd Haemostatic compositions
CN107686506B (zh) * 2016-08-05 2021-03-30 首都医科大学 华法林-4-o-乙酰-gprp,其合成,活性和应用
CN108976284B (zh) * 2017-05-31 2021-11-30 首都医科大学 含Gly-Pro-Arg-Pro的五肽修饰的华法林,其合成,活性和应用
CN108976285B (zh) * 2017-05-31 2021-11-30 首都医科大学 Gly-Pro-Arg-Pro-AA修饰的华法林,其合成,活性和应用
EP3618853B1 (en) * 2018-04-24 2020-09-09 Fibriant B.V. Fibrinogen gamma prime variants for use in treating an infection
CN115010784B (zh) * 2022-05-16 2023-03-31 江南大学 一种ace抑制肽及其应用

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Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3095468A1 (en) * 2006-11-27 2016-11-23 Haemostatix Limited Biogel
WO2008065388A3 (en) * 2006-11-27 2009-11-26 Haemostatix Limited Biogel
US9913876B2 (en) 2006-11-27 2018-03-13 Haemostatix Limited Biogel
US9339584B2 (en) 2006-11-27 2016-05-17 Haemostatix Limited Biogel
US20100113368A1 (en) * 2007-03-21 2010-05-06 Luppo Edens Cholesterol lowering protein hydrolysates
WO2008113796A1 (en) * 2007-03-21 2008-09-25 Dsm Ip Assets B.V. Cholesterol lowering protein hydrolysates
WO2009046843A1 (en) * 2007-09-11 2009-04-16 Mondobiotech Laboratories Ag Therapeutic uses of peptides kvlpvpq and/or tdvngdgrhdl
WO2009046844A1 (en) * 2007-09-11 2009-04-16 Mondobiotech Laboratories Ag Therapeutic uses of peptide tdvngdgrhdl
WO2012104638A1 (en) 2011-02-01 2012-08-09 Haemostatix Limited Therapeutic agents with improved fibrinogen binding
US9724379B2 (en) 2011-02-01 2017-08-08 Haemostatix Limited Therapeutic agents with improved fibrinogen binding
WO2013021353A1 (en) * 2011-08-11 2013-02-14 Bar-Ilan University Surface modified proteinaceous spherical particles and uses thereof
US9504759B2 (en) 2011-08-11 2016-11-29 Bar-Ilan University Surface modified proteinaceous spherical particles and uses thereof
RU2661036C2 (ru) * 2012-02-01 2018-07-11 Гемостатикс Лимитед Средство для гемостатической обработки раны
US9808553B2 (en) 2012-02-01 2017-11-07 Haemostatix Limited Haemostatic wound dressing
GB2501348A (en) * 2012-02-01 2013-10-23 Haemostatix Ltd Haemostatic wound dressing
WO2013114132A1 (en) * 2012-02-01 2013-08-08 Haemostatix Limited Haemostatic wound dressing
GB2501348B (en) * 2012-02-01 2020-06-24 Haemostatix Ltd Haemostatic wound dressing
WO2014197816A1 (en) * 2013-06-06 2014-12-11 Massachusetts Institute Of Technology Stimulus responsive nanocomplexes and methods of use thereof
KR20160105820A (ko) * 2014-01-08 2016-09-07 해모스타틱스 리미티드 피브리노겐-결합 펩타이드를 포함하는 펩타이드 덴드리머
WO2015104544A1 (en) * 2014-01-08 2015-07-16 Haemostatix Limited Peptide dendrimers comprising fibrinogen-binding peptides
US10994047B2 (en) 2014-01-08 2021-05-04 Haemostatix Limited Peptide dendrimers comprising fibrinogen-binding peptides
KR102410065B1 (ko) 2014-01-08 2022-06-16 해모스타틱스 리미티드 피브리노겐-결합 펩타이드를 포함하는 펩타이드 덴드리머
US11192936B2 (en) 2014-01-10 2021-12-07 Bioverativ Therapeutics Inc. Factor VIII chimeric proteins and uses thereof
US12161696B2 (en) 2016-12-02 2024-12-10 Bioverativ Therapeutics Inc. Methods of treating hemophilic arthropathy using chimeric clotting factors
US12030925B2 (en) 2018-05-18 2024-07-09 Bioverativ Therapeutics Inc. Methods of treating hemophilia A

Also Published As

Publication number Publication date
US20090203619A1 (en) 2009-08-13
EP2335737A2 (en) 2011-06-22
US20130029913A1 (en) 2013-01-31
WO2007015107A3 (en) 2007-07-26
GB0516091D0 (en) 2005-09-14
GB2429153C (en) 2019-01-23
GB0615545D0 (en) 2006-09-13
AU2006274685A1 (en) 2007-02-08
CN101267843A (zh) 2008-09-17
IL189105A0 (en) 2008-08-07
CA2625917A1 (en) 2007-02-08
GB2429153B (en) 2010-03-10
EP2335737A3 (en) 2013-09-25
JP2009505964A (ja) 2009-02-12
GB2429153A (en) 2007-02-21
EP1919508B1 (en) 2015-02-25
EP1919508A2 (en) 2008-05-14

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