WO2015184008A1 - Fucosidase from bacteroides and methods using the same - Google Patents

Fucosidase from bacteroides and methods using the same Download PDF

Info

Publication number
WO2015184008A1
WO2015184008A1 PCT/US2015/032744 US2015032744W WO2015184008A1 WO 2015184008 A1 WO2015184008 A1 WO 2015184008A1 US 2015032744 W US2015032744 W US 2015032744W WO 2015184008 A1 WO2015184008 A1 WO 2015184008A1
Authority
WO
WIPO (PCT)
Prior art keywords
fucosidase
fucose
linked
seq
glycoconjugate
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/US2015/032744
Other languages
English (en)
French (fr)
Inventor
Chi-Huey Wong
Tsung-I Tsai
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.)
Academia Sinica
Original Assignee
Academia Sinica
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 AU2015267051A priority Critical patent/AU2015267051B2/en
Priority to KR1020167036507A priority patent/KR20170010003A/ko
Priority to EP15800191.7A priority patent/EP3149161B1/en
Priority to EP21162500.9A priority patent/EP3904388A1/en
Priority to KR1020227043794A priority patent/KR102576850B1/ko
Priority to CA2950577A priority patent/CA2950577A1/en
Application filed by Academia Sinica filed Critical Academia Sinica
Priority to JP2016569720A priority patent/JP7093612B2/ja
Priority to CN201580027982.6A priority patent/CN106661562A/zh
Publication of WO2015184008A1 publication Critical patent/WO2015184008A1/en
Priority to IL249183A priority patent/IL249183B/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/14—Preparation of compounds containing saccharide radicals produced by the action of a carbohydrase (EC 3.2.x), e.g. by alpha-amylase, e.g. by cellulase, hemicellulase
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C07K16/108—Orthomyxoviridae (F), e.g. influenza virus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • 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)
    • 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)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/575—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/5758—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites
    • G01N33/5759—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites involving compounds localised on the membrane of tumour or cancer cells
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/72—Increased effector function due to an Fc-modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/01051—Alpha-L-fucosidase (3.2.1.51)
    • Y—GENERAL 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • Fucose is an important component of many O- or N-linked oligosaccharide structures of glycoconjugates. Fucose-containing glycans are involved in numerous biological events, including development and apoptosis, and are involved in the pathology of inflammation, cancer, and cystic fibrosis. Defucosylation of the glycoconjugates is an important process for understanding the biological effects of the glycoconjugates.
  • a-L-fucosidases are exo-glycosidases, responsible for the removal of fucose residues from the non-reducing end of glycoconjugates by hydrolyzing a-(l,2), a-(l,3), a-(l,4), and a-(l,6) linkages of fucoses attached, primarily to galactose or N-acetylglucosamine.
  • ADCC antibody-dependent cellular cytotoxicity
  • ADCC is triggered upon the binding of lymphocyte receptors (FccRs) to the antibody Fc region.
  • ADCC activity is dependent on the amount of fucose attached to the innermost GlcNAc of N- linked Fc oligosaccharide via an a-(l,6) linkage.
  • the present invention provides the compositions and methods for the improved enzymatic hydrolysis of fucose in vitro.
  • the present invention is useful for the efficient cleavage of core fucose in native glycoproteins without denaturation or functional deterioration of glycoproteins.
  • the compositions and methods of the invention can facilitate the Fc glycoengineering of Fc fusion proteins or antibodies, such as therapeutic antibodies.
  • This invention also provides the application of glycan sequencing for distinguishing fucose position on a glycoconjugate.
  • the glycoconjugate may be a glycolipid, glycoprotein, oligosaccharide, or glycopeptide.
  • the present invention relates to an a-fucosidase comprising a polypeptide having at least 85% sequence identity to SEQ ID NO: 1.
  • the ⁇ -fucosidase comprises a polypeptide having at least 88% sequence identity to SEQ ID NO: 1.
  • the a-fucosidase comprises a polypeptide having the sequence identity to SEQ ID NO: 1.
  • the a-fucosidase comprises a polypeptide having the sequence identity to SEQ ID NO: 2. SEQ ID NOs: 1 and 2 share 88% sequence identity.
  • the fucosidase described herein can hydrolyze one or more a(l,2), a(l,3), a(l,4), and a(l,6)-linked fucoses.
  • the fucoses may be present in N- and/or O- linked glycans in a glycoconjugate.
  • the a-fucosidase is a recombinant Bacteroides - fucosidase.
  • the a-fucosidase exhibits pH optimum at 4-9.
  • the present invention relates to a composition
  • a composition comprises the a- fucosidase described above.
  • the composition may further comprise at least one glycosidase.
  • the glycosidase may be an exoglycosidase.
  • the exoglycosidase includes, but not limited to, sialidase, galactosidase, alpha-fucosidase, and bariants thereof.
  • the glycosidase may be an endoglycosidase.
  • the endoglycosidase includes, but not limited to, Endo-beta-N-acetylglucosaminidases (NAG), EndoA, EndoFl, EndoF2, EndoF3, EndoH, EndoM, EndoS, and variants thereof.
  • NAG Endo-beta-N-acetylglucosaminidases
  • the composition of the invention is useful for making defucosylation of a glycoconjugate in vitro.
  • the composition described herein is useful for making core defucosylation of glycoproteins in vitro.
  • the core defucosylation is core a(l,6) defucosylation.
  • the core defucosylation is core a(l,3) defucosylation. The defucosylation can be performed without denaturation or functional deterioration of glycoproteins.
  • Another aspect of the invention provides a method for making defucosylation of a glycoconjugate in vitro.
  • the inventive method comprises the step of contacting the
  • the glycoconjugate comprises one or more fucoses selected from a(l,2), a(l,3), a(l,4), and a(l,6)-linked fucoses.
  • the fucoses may be present in N- and/or O- linked glycans in a glycoconjugate.
  • the glycoconjugate is a glycoprotein.
  • the glycoprotein comprises a core fucose.
  • the core fucose is a core a- (l,3)-linked fucose or a core a-(l,6)-linked fucose.
  • the method further comprises contacting the glycoconjugate with at least one glycosidase.
  • the glycosidas is an endoglycosidase.
  • Endoglycosidase is used to trim off the variable portions of an oligosaccharide in the N-glycan.
  • Examples of endoglycosidases used herein include, but not limited to, Endo-beta-N- acetylglucosaminidases (NAG), EndoA, EndoF l, EndoF2, EndoF3, EndoH, EndoM, EndoS, and variants thereof.
  • NAG Endo-beta-N- acetylglucosaminidases
  • the glycoconjugate can be treated with an endoglycosidase and an a-fucosidase sequentially or simultaneously.
  • the core defucosylation may be core a(l,3) defucosylation or a(l,6) defucosylation.
  • Figure 1 shows the biochemical properties of BfFucH.
  • Figure 3. shows the time course of of BfFucH treatment for Rituxan.
  • N-glycans have not been able to be achieved enzymatically in vitro, mainly because N-glycans are embedded between two Fc domains.
  • the enzymatic defucosylation efficiency is much lower due to steric hindrance, i.e., access of a- fucosidase to fucose residues is blocked by potions of the Fc domains.
  • a number of a-fucosidases are known in the art. Examples include a-fucosidases from Turbo cornutus, Charonia lampas, Bacillus fulminans, Aspergillus niger, Clostridium perfringens, Bovine kidney (Glyko), Chicken liver (Tyagarajan et al., 1996, Glycobiology 6:83- 93) and ⁇ -fucosidase II from Xanthomonas manihotis (Glyko, PROzyme). Some fucosidase are also commercially available (Glyko, Novato, Calif; PROzyme, San Leandro, Calif;
  • WO 2013/12066 disclosed the defucosylation of (Fucod ,6) GlcNAc-Rituximab by an a-fucosidase from bovine kidney.
  • the present disclosure relates to an unexpected discovery of a bacterial a-fucosidase that is able to efficiently cleave core fucose from N-linked glycans.
  • the present disclosure relates to an unexpected discovery of a bacterial a-fucosidase that is able to efficiently cleave core fucoses from N-linked glycans.
  • the a-fucosidase may be an a-fucosidase from Bacteroides fragilis (BfFucH). In some examples, the a-fucosidase may be an a-fucosidase from Bacteroides thetaiotaomicron (BtFucH).
  • the a-fucosidase can be expressed from bacteria, yeast, baculovirus/insect, or mammalian cells.
  • the a-fucosidase can be a recombinant Bacteroides a-fucosidase. In some embodiments, the a-fucosidase can be a recombinant Bacteroides a-fucosidase expressed from E. coli.
  • the a-fucosidase can hydrolyze one or more a(l,2), a(l,3), a(l,4), and a(l,6)-linked fucoses.
  • the fucose may be present in N- and/or O- linked glycans in a glycoconjugate.
  • the fucose can be a core a-(l,3) fucose or a core a-(l,6) fucose.
  • Scheme 1 shows various fucose-containing glycoconjugates.
  • Examples of the substrates suitable for the enzyme include, but not limited to, milk oligosaccharides, cancer associated carbohydrate antigens such as Globo H, Lewis blood groups (a, b, x, y), and sialyl Lewis a (SLe a ) and x (SLe x ).
  • the a- fucosidase can hydrolyze sialyl Lewis a (SLe a ) and x (SLe x ) withour cleaving the terminal sialic acid.
  • Milk oligosaccharides may bear a-(l,2), a-(l,3) and/or a-(l,4) linked fucoses.
  • the present invention also relates to a compostion of the a-fucosidase described above.
  • the a-fucosidase comprises a polypeptide having at least 85% sequence identity to SEQ ID NO: 1.
  • the a-fucosidase comprises a polypeptide having at least 88% identity to SEQ ID NO: 1 , or a functional variant thereof.
  • the a- fucosidase comprises a polypeptide having an amino acid sequence of SEQ ID NO: 1.
  • the a-fucosidase comprises a polypeptide having an amino acid sequence of SEQ ID NO: 2.
  • SEQ ID NO: 2 has 88% sequence identity to SEQ ID NO: 1.
  • Variant polypeptide as described herein are those for which the amino acid sequence varies from that in SEQ ID NO: 1 or 2, but exhibit the same or similar function of the enzyme comprising the polypeptide having an amino acid sequence of SEQ ID NO: 1 or 2.
  • percent (%) sequence identity with respect to a sequence is defined as the percentage of amino acid residues in a candidate polypeptide sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.
  • the polypeptide of the a-fucosidase of the invention may be derivatized or modified to assist with their isolation or purification.
  • the polypeptide for use in the invention is derivatized or modified by addition of a ligand which is capable of binding directly and specifically to a separation means.
  • the polypeptide is derivatized or modified by addition of one member of a binding pair and the separation means comprises a reagent that is derivatized or modified by addition of the other member of a binding pair. Any suitable binding pair can be used.
  • the polypeptide for use in the invention is derivatized or modified by addition of one member of a binding pair
  • the polypeptide is preferably histidine-tagged or biotin-tagged.
  • the amino acid coding sequence of the histidine or biotin tag is included at the gene level and the proteins are expressed recombinantly in E. coli.
  • the histidine or biotin tag is typically present at one end of the polypeptide, either at the N-terminus or at the C-terminus.
  • the histidine tag typically consists of six histidine residues, although it can be longer than this, typically up to 7, 8, 9, 10 or 20 amino acids or shorter, for example 5, 4, 3, 2 or 1 amino acids.
  • the histidine tag may contain one or more amino acid substitutions, preferably conservative substitutions as defined above.
  • composition of the invention can be used for making defucosylation of a glycoconjugate in vitro.
  • inventive method comprises the step of contacting the
  • the glycoconjugate comprises one or more fucoses selected from a-(l,2), a-(l,3), a-(l,4), and a-(l,6)-linked fucoses.
  • the fucoses may be present in N- and/or O- linked glycans in a glycoconjugate.
  • the glycoconjugate is a glycoprotein.
  • the glycoprotein comprises a core fucose.
  • the core fucose is a core a- (1,3) linked fucose or a core a-(l,6) linked fucose.
  • the method further comprises contacting the glycoconjugate with at least one glycosidase.
  • the glycosidas is an endoglycosidase.
  • Endoglycosidase is used to trim off the variable portions of an oligosaccharide in the N-glycan.
  • Examples of endoglycosidases used herein include, but not limited to, Endo-beta-N- acetylglucosaminidases (NAG), EndoA, EndoF l, EndoF2, EndoF3, EndoH, EndoM, EndoS, and variants thereof.
  • the glycoconjugate can be treated with an endoglycosidase and an a-fucosidase sequentially or simultaneously.
  • the core defucosylation may be core a(l,3) defucosylation or a(l,6) defucosylation.
  • the method of the invention can be useful for making Fc glycoengineering from monoclonal antibodies.
  • Exemplary methods of engineering are described in, for example, Wong et al USSN12/959,351, the contents of which is hereby incorporated by reference.
  • the monoclonal antibodies are therapeutic monoclonal antibodies.
  • the method for making a homogeneously glycosylated monoclonal antibody comprises the steps of (a) contacting a monoclonal antibody with an a-fucosidase and at least one endoglycosidase, thereby yielding a defucosylated antibody having a single N-acetylglucosamine (GlcNAc), and (b) adding a carbohydrate moiety to GlcNAc under suitable conditions.
  • a monoclonal antibody with an a-fucosidase and at least one endoglycosidase thereby yielding a defucosylated antibody having a single N-acetylglucosamine (GlcNAc)
  • GlcNAc N-acetylglucosamine
  • the glycan can be prepared by treatment with endo-GlcNACase and exemplary fucosidase, then followed by exemplary endo-S mutant and a glycan oxazoline.
  • the monoclonal antibody according to the method of the invention is Rituximab.
  • the carbohydrate moiety according to the method the invention is sleeted from the group consisting of Sia 2 (a2- 6)Gal 2 GlcNAc 2 Man 3 GlcNAc, Sia 2 (a2-6)Gal 2 GlcNAc 3 Man 3 GlcNAc, Sia 2 (a2- 3)Gal 2 GlcNAc 2 Man 3 GlcNAc, Sia 2 (a2-3)Gal 2 GlcNAc 3 Man 3 GlcNAc, Sia 2 (a2-3/a2- 6)Gal 2 GlcNAc 2 Man 3 GlcNAc, Sia 2 (a2-6/a2-3)Gal 2 GlcNAc 2 Man 3 GlcNAc, Sia 2 (a2-3/a2- 6)Gal 2 GlcNAc 3 Man 3 GlcNAc, Sia 2 (a2-3/a2- 6)Gal 2 GlcNAc 3 Man 3 GlcNA
  • the carbohydrate moiety is a sugar oxazoline.
  • Step (b) in the method of the invention may lead to sugar chain extension.
  • One method for sugar chain extension is through an enzyme-catalyzed glycosylation reaction. It is well known in the art that glycosylation using a sugar oxazoline as the sugar donor among the enzyme-catalyzed glycosylation reactions is useful for synthesizing oligosaccharides because the glycosylation reaction is an addition reaction and advances without any accompanying elimination of acid, water, or the like. (Fujita, et al, Biochim. Biophys. Acta 2001, 1528, 9-14)
  • Suitable conditions in step (b) include incubation of the reaction mixture for at least 20 minutes, 30 minutes, 40 minutes, 50 minutes, 60 minutes, 70 minutes, 80 minutes, 90 minutes or 100 minutes, preferably less than 60 minutes. Incubation preferably takes place at room temperature, more preferably at approximately 20°C, 25 °C, 30°C, 35 °C, 40°C or 45 °C, and most preferably at approximately 37°C.
  • the terms “fucose” and “ L-fucose” are used interchangeably.
  • core fucose and “ core fucose residue” are used interchangeably and refer to a fucose in a 1,3 -position or al,6-position linked to the asparagine- bound N-acetylglucosamine.
  • a-(l,2) Fucosidase refers to an exoglycosidase that specifically catalyzes the hydrolysis of a-(l,2) linked L-fucose residues from oligosaccharides.
  • a-(l,4) Fucosidase refers to an exoglycosidase that specifically catalyzes the hydrolysis of a-(l,4) linked L-fucose residues from oligosaccharides.
  • glycocan refers to a polysaccharide, oligosaccharide or monosaccharide. Glycans can be monomers or polymers of sugar residues and can be linear or branched.
  • a glycan may include natural sugar residues (e.g., glucose, N-acetylglucosamine, N- acetyl neuraminic acid, galactose, mannose, fucose, hexose, arabinose, ribose, xylose, etc.) and/or modified sugars (e.g., 2'-fluororibose, 2'-deoxyribose, phosphomannose, 6' sulfo N- acetylglucosamine, etc).
  • natural sugar residues e.g., glucose, N-acetylglucosamine, N- acetyl neuraminic acid, galactose, mannose, fucose, hexose, arabinose, ribose, xylose, etc.
  • modified sugars e.g., 2'-fluororibose, 2'-deoxyribose, phosphomannose,
  • N-glycan As used herein, the terms "N-glycan”, “N-linked glycan”, “N-linked glycosylation”, “Fc glycan” and “Fc glycosylation” are used interchangeably and refer to an N-linked oligosaccharide attached by an N-acetylglucosamine (GlcNAc) linked to the amide nitrogen of an asparagine residue in a Fc-containing polypeptide.
  • GlcNAc N-acetylglucosamine
  • Fc-containing polypeptide refers to a polypeptide, such as an antibody, which comprises an Fc region.
  • glycosylation pattern and “glycosylation profile” are used interchangeably and refer to the characteristic "fingerprint” of the N-glycan species that have been released from a glycoprotein or antibody, either enzymatically or chemically, and then analyzed for their carbohydrate structure, for example, using LC-HPLC, or MALDI-TOF MS, and the like. See, for example, the review in Current Analytical Chemistry, Vol. 1, No. 1 (2005), pp. 28-57; herein incorporated by reference in its entirety.
  • glycoengineered Fc when used herein refers to N-glycan on the Fc region has been altered or engineered either enzymatically or chemically.
  • Fc glycoengineering refers to the enzymatic or chemical process used to make the glycoengineered Fc.
  • the terms “homogeneous”, “uniform”, “uniformly” and “homogeneity” in the context of a glycosylation profile of Fc region are used interchangeably and are intended to mean a single glycosylation pattern represented by one desired N-glycan species, with no trace amount of precursor N-glycan.
  • immunoglobulin and “immunoglobulin molecule” are used interchangeably.
  • molecule can also include antigen binding fragments.
  • glycoconjugate encompasses all molecules in which at least one sugar moiety is covalently linked to at least one other moiety.
  • the term specifically encompasses all biomolecules with covalently attached sugar moieties, including for example N-linked glycoproteins, O-linked glycoproteins, glycolipids, proteoglycans, etc.
  • glycolipid refers to a lipid that contains one or more covalently linked sugar moieties (i.e., glycans).
  • the sugar moiety(ies) may be in the form of monosaccharides, disaccharides, oligosaccharides, and/or polysaccharides.
  • the sugar moiety(ies) may comprise a single unbranched chain of sugar residues or may be comprised of one or more branched chains.
  • sugar moieties may include sulfate and/or phosphate groups.
  • glycoproteins contain O-linked sugar moieties; in certain embodiments, glycoproteins contain N-linked sugar moieties.
  • glycoprotein refers to amino acid sequences that include one or more oligosaccharide chains (e.g., glycans) covalently attached thereto.
  • exemplary amino acid sequences include peptides, polypeptides and proteins.
  • exemplary glycoproteins include glycosylated antibodies and antibody-like molecules (e.g., Fc fusion proteins).
  • Exemplary antibodies include monoclonal antibodies and/or fragments thereof, polyclonal antibodies and/or fragments thereof, and Fc domain containing fusion proteins (e.g., fusion proteins containing the Fc region of IgGl, or a glycosylated portion thereof).
  • N-glycan refers to a polymer of sugars that has been released from a glycoconjugate but was formerly linked to the glycoconjugate via a nitrogen linkage (see definition of N-linked glycan below).
  • O-glycan refers to a polymer of sugars that has been released from a glycoconjugate but was formerly linked to the glycoconjugate via an oxygen linkage (see definition of O-linked glycan below).
  • a functional variant of a wild-type enzyme possesses the same enzymatic activity as the wild-type counterpart and typically shares a high amino acid sequence homology, e.g., at least about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the amino acid sequence of the wild-type counterpart.
  • the "percent identity" of two amino acid sequences is determined using the algorithm of Karlin and Altschul Proc. Natl. Acad. Sci. USA 87:2264-68, 1990, modified as in Karlin and Altschul Proc. Natl. Acad.
  • a functional variant can have various mutations, including addition, deletion, or substitution of one or more amino acid residues. Such a variant often contain mutations in regions that are not essential to the enzymatic activity of the wild-type enzyme and may contain no mutations in functional domains or contain only conservative amino acid substitutions. The skilled artisan will realize that conservative amino acid substitutions may be made in lipoic acid ligase mutants to provide functionally equivalent variants, i.e., the variants retain the functional capabilities of the particular lipoic acid ligase mutant.
  • a "conservative amino acid substitution” refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the amino acid substitution is made.
  • Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references which compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et al, eds., Second Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1989, or Current Protocols in Molecular Biology. F.M. Ausubel, et al, eds., John Wiley & Sons, Inc., New York.
  • Conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D.
  • Any of the enzymes involved in the deglycosylation system can be prepared via routine technology.
  • the enzyme is isolated form a natural source.
  • the enzyme is prepared by routine recombinant technology.
  • the coding sequence of a target enzyme can be subjected to coden optimization based on the host cell used for producing the enzyme. For example, when E.
  • coli cells are used as the host for producing an ezyme via recombinant technology, the gene encoding that enzyme can be modified such that it contains codons commonly used in E. coli.
  • the details of one or more embodiments of the invention are set forth in the description below. Other features or advantages of the present invention will be apparent from the following drawings and detailed description of several embodiments, and also from the appending claims.
  • the a-fucosidases were amplified by PCR from Bacteroides fragilis NCTC 9343 genomic DNA (ATCC 25285) and Bacteroides Thetaiotaomicron VPI-5482 (ATCC 29148), respectively, and cloned into pET47b+ (EMD Biosciences, San Diego, CA) with N-termial poly- histine with internal AcTEV protease cutting site.
  • Endo F l (GenBank: AAA24922.1), Endo F2 (GenBank: AAA24923.1), Endo F3 (GenBank: AAA24924.1), Endo H (GenBank: AAA26738.1) and PNGase F (Genbank: GenBank:
  • J05449.1 were codon optimized for E.coli, and cloned into pET28a with MBP fusion in N- terminus, respectively. All sequences of the clones were first confirmed by Applied Biosystems 3730 DNA Analyzer.
  • a pa r o pr mers or orwar F) an reverse R) PCR react ons to amp y coding sequence of each gene.
  • Protein expression constructs were transformed into BL21(DE3) (EMD Biosciences, San Diego, CA) for protein expression using 0.2 mM isopropyl ⁇ -D-thiogalactopyranoside (IPTG) in 16°C for 24hours. Cells were disrupted by microfluidizer and then centrifuged. Supernatants were collected and loaded onto Ni-NTA agarose column (QIAGEN GmbH, Hilden, Germany) and washed with ten folds of washing buffer (sodium phosphate buffer (pH 7.0), 300 niM sodium chloride, and 10 mM imidazole).
  • washing buffer sodium phosphate buffer (pH 7.0), 300 niM sodium chloride, and 10 mM imidazole.
  • Elution was employed by two folds of elution buffer (sodium phosphate buffer (pH 7.0), 300 mM sodium chloride, and 250 mM imidazole), followed bybuffer exchanging into reaction buffer by Amicon Ultra- 15 10K (EMD Millipore Chemicals, Billerica, MA). Protein purity was examined by SDS-PAGE and quantitative protein concentration was measured by Qubit® Protein Assay Kits (Invitrogen, Carlsbad, CA). The recombinant fucosidase with his-tag followed by Ni-NTA column purification resulted in a yield of 60 mg/ Lwith greater than 95% purity. Protein concentration was determined according to the method of Brandford (Protein Assay; Bio-Rad, Hercules, CA, USA) with bovine serum albumin as standards. The purity and molecular mass of the enzyme was examined by SDS-PAGE.
  • the purified fucosidase from Bacteroides fragilis exhibited a molecular mass of about 50 kDa in sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) which is close to the theoretical molecular weight of 47.3 kDa.
  • BfFucH preformed well at mild condition (pH 7.0-7.5).
  • BfFucH is not affected by certain divalent metal ions, and exogenous addition of metal ions did not influence the activity.
  • Ni 2+ can dramatically reduce the enzymatic activity by 60%.
  • Zn 2+ and Cu 2+ can completely abolish the enzymatic activity.
  • the chelator EDTA showed no effect on the enzymatic activity, indicating the metal ions do not participate in the catalytic reaction.
  • the enzyme is funationally active and stable at room temperate and at 4°C.
  • the fucosidases described herein can be used to determine the fucose position in N- glycan.
  • the BfFucH hydrolysis activity on N-glycans with various fucoses attached at different positions was evaluated.
  • Two synthetic glycopeptides, 0800F and 0823F, were prepared. Both glycopeptides have the fucoses bound to outer GlcNAc and the innermost GlcNAc at the glycosylation site, respectively.
  • LPS lipopolysaccharide
  • FDH formaldehyde dehygrogenase
  • Aleuria aurantia possesses a fucose-specific lectin (AAL) that is widely used as a specific probe for fucose.
  • AAL recognizes and binds specifically to fucose and terminal fucose residues on complex oligo saccharides and glycoconjugates.
  • AAL can be used to determine the core defucosylation.
  • Endoglycosidase is useful for trimming off the variable portions of an oligosaccharide in the N-glycan.
  • TNFa tumor necrosis factor-alpha
  • Adalimumab Humanab
  • Anti-tumor necrosis factor-alpha (TNFa) antibody was purchased from (North Chicago, IL).
  • Anti-human CD20 mouse/human chimeric IgGl rituximab was purchased from Genentech, Inc. (South San Francisco, CA)/IDEC Pharmaceutical (San Diego, CA).
  • TNF receptor-Fc fusion protein Etanercept Enbrel® was purchased from Wyeth Pharmaceuticals (Hampshire, UK).
  • Epoetin beta (Recormon®) was purchased from Hoffmann-La Roche Ltd (Basel, Switzerland).
  • Interferon la was purchased from EMD Serono, Inc. (Boston, MA).
  • Para-Nitrophenyl a- or ⁇ -monosaccharide, Lewis sugars, blood type sugars and human milk oligosaccharides were purchased from Carbosynth Limited. (Berkshire, UK).
  • Enzyme activity was measured at 25°C in 50mM sodium phosphate buffer, pH 7.0, using pNP-a-L-Fuc (p-nitrophenyl-a-L-Fuc) as a substrate, as standard assay condition.
  • pNP-a-L-Fuc p-nitrophenyl-a-L-Fuc
  • One unit of a-L- fucosidase activity was defined as the formation of 1 ⁇ of pNP and Fuc from the pNP-a-L-Fuc per minute in 50 mM sodium phosphate buffer, pH 7.0, at 25°C.
  • the assay for metal requirement was performed in standard assay condition. Enzymes were mixed with metal ion (Mg 2+ , Mn 2+ , Ca 2+ , Zn 2+ , Co 2+ , or Ni 2+ , Fe 2+ , Cu 2+ ) in a final concentration of 5mM, in the presence and absence of EDTA. All reactions were performed in triplicate for statistical evaluation.
  • metal ion Mg 2+ , Mn 2+ , Ca 2+ , Zn 2+ , Co 2+ , or Ni 2+ , Fe 2+ , Cu 2+
  • the fucose dehydrogenase-based assay was slightly modified from previous reports. Unlike other fucose dehydrogenases from Pseudomonas sp sold by Sigma- Aldrich, which are active only react with NADP+, the recombinant form of FDH from Mesorhizobium loti are functional with only NAD+. The NADH formed was measured by NADPH fluorescence at around 450nm when excited with 340nm by multimode plate readers (SpectraMax M5, Molecular Devices) at 25°C. By using this method, fucosyl-conjugates in various
  • oligosaccharides such as Lewis sugar and human milk oligosaccharides (HMOs) were quantitated within 5 min.
  • glycoproteins were buffer exchanging by reaction buffer 50mM sodium phosphate buffer (pH 7.0).
  • reaction buffer 50mM sodium phosphate buffer pH 7.0.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Virology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Mycology (AREA)
  • Communicable Diseases (AREA)
  • Urology & Nephrology (AREA)
  • Endocrinology (AREA)
  • Cell Biology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
PCT/US2015/032744 2014-05-27 2015-05-27 Fucosidase from bacteroides and methods using the same Ceased WO2015184008A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
KR1020167036507A KR20170010003A (ko) 2014-05-27 2015-05-27 박테로이드 기원의 푸코시다제 및 이의 사용 방법
EP15800191.7A EP3149161B1 (en) 2014-05-27 2015-05-27 Fucosidase from bacteroides and methods using the same
EP21162500.9A EP3904388A1 (en) 2014-05-27 2015-05-27 Fucosidase from bacteroides and methods using the same
KR1020227043794A KR102576850B1 (ko) 2014-05-27 2015-05-27 박테로이드 기원의 푸코시다제 및 이의 사용 방법
CA2950577A CA2950577A1 (en) 2014-05-27 2015-05-27 Fucosidase from bacteroides and methods using the same
AU2015267051A AU2015267051B2 (en) 2014-05-27 2015-05-27 Fucosidase from bacteroides and methods using the same
JP2016569720A JP7093612B2 (ja) 2014-05-27 2015-05-27 Ｂａｃｔｅｒｏｉｄｅｓ由来のフコシダーゼおよびそれを使用する方法
CN201580027982.6A CN106661562A (zh) 2014-05-27 2015-05-27 得自类杆菌属的岩藻糖苷酶及其用途
IL249183A IL249183B (en) 2014-05-27 2016-11-24 Fucosidase from bacteroides and methods using the same

Applications Claiming Priority (10)

Application Number Priority Date Filing Date Title
US201462003136P 2014-05-27 2014-05-27
US201462003104P 2014-05-27 2014-05-27
US62/003,104 2014-05-27
US62/003,136 2014-05-27
US201462003908P 2014-05-28 2014-05-28
US62/003,908 2014-05-28
US201462020199P 2014-07-02 2014-07-02
US62/020,199 2014-07-02
US201562110338P 2015-01-30 2015-01-30
US62/110,338 2015-01-30

Publications (1)

Publication Number Publication Date
WO2015184008A1 true WO2015184008A1 (en) 2015-12-03

Family

ID=54699741

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2015/032744 Ceased WO2015184008A1 (en) 2014-05-27 2015-05-27 Fucosidase from bacteroides and methods using the same
PCT/US2015/032745 Ceased WO2015184009A1 (en) 2014-01-16 2015-05-27 Compositions and methods relating to universal glycoforms for enhanced antibody efficacy

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/US2015/032745 Ceased WO2015184009A1 (en) 2014-01-16 2015-05-27 Compositions and methods relating to universal glycoforms for enhanced antibody efficacy

Country Status (12)

Country Link
US (4) US11319567B2 (https=)
EP (4) EP3904388A1 (https=)
JP (5) JP6894239B2 (https=)
KR (5) KR20170010003A (https=)
CN (3) CN106661562A (https=)
AU (3) AU2015267051B2 (https=)
CA (2) CA2950423A1 (https=)
DK (2) DK3149045T3 (https=)
FI (1) FI3149045T3 (https=)
IL (2) IL249195B (https=)
TW (2) TWI654202B (https=)
WO (2) WO2015184008A1 (https=)

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9879042B2 (en) 2014-09-08 2018-01-30 Academia Sinica Human iNKT cell activation using glycolipids
US9975965B2 (en) 2015-01-16 2018-05-22 Academia Sinica Compositions and methods for treatment and detection of cancers
US9982041B2 (en) 2014-01-16 2018-05-29 Academia Sinica Compositions and methods for treatment and detection of cancers
US9981030B2 (en) 2013-06-27 2018-05-29 Academia Sinica Glycan conjugates and use thereof
US10005847B2 (en) 2014-05-27 2018-06-26 Academia Sinica Anti-HER2 glycoantibodies and uses thereof
US10023892B2 (en) 2014-05-27 2018-07-17 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10086054B2 (en) 2013-06-26 2018-10-02 Academia Sinica RM2 antigens and use thereof
US10087236B2 (en) 2009-12-02 2018-10-02 Academia Sinica Methods for modifying human antibodies by glycan engineering
US10111951B2 (en) 2013-09-06 2018-10-30 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US10118969B2 (en) 2014-05-27 2018-11-06 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10119972B2 (en) 2014-03-27 2018-11-06 Academia Sinica Reactive labelling compounds and uses thereof
US10130714B2 (en) 2012-04-14 2018-11-20 Academia Sinica Enhanced anti-influenza agents conjugated with anti-inflammatory activity
US10150818B2 (en) 2014-01-16 2018-12-11 Academia Sinica Compositions and methods for treatment and detection of cancers
US10214765B2 (en) 2012-08-18 2019-02-26 Academia Sinica Cell-permeable probes for identification and imaging of sialidases
US10260056B2 (en) 2017-03-17 2019-04-16 New England Biolabs, Inc. Cleavage of fucose in N-glycans
US10274488B2 (en) 2008-07-15 2019-04-30 Academia Sinica Glycan arrays on PTFE-like aluminum coated glass slides and related methods
US10317393B2 (en) 2007-03-23 2019-06-11 Academia Sinica Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells
US10338069B2 (en) 2010-04-12 2019-07-02 Academia Sinica Glycan arrays for high throughput screening of viruses
US10336784B2 (en) 2016-03-08 2019-07-02 Academia Sinica Methods for modular synthesis of N-glycans and arrays thereof
US10342858B2 (en) 2015-01-24 2019-07-09 Academia Sinica Glycan conjugates and methods of use thereof
US10495645B2 (en) 2015-01-16 2019-12-03 Academia Sinica Cancer markers and methods of use thereof
US10538592B2 (en) 2016-08-22 2020-01-21 Cho Pharma, Inc. Antibodies, binding fragments, and methods of use
WO2021026264A1 (en) * 2019-08-05 2021-02-11 Cho Pharma, Inc. Fusion protein for remodeling antibody glycoform
US11332523B2 (en) 2014-05-28 2022-05-17 Academia Sinica Anti-TNF-alpha glycoantibodies and uses thereof
US11377485B2 (en) 2009-12-02 2022-07-05 Academia Sinica Methods for modifying human antibodies by glycan engineering
WO2022261021A1 (en) * 2021-06-07 2022-12-15 Amgen Inc. Using fucosidase to control afucosylation level of glycosylated proteins
US11884739B2 (en) 2014-05-27 2024-01-30 Academia Sinica Anti-CD20 glycoantibodies and uses thereof

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201201314D0 (en) * 2012-01-26 2012-03-07 Isis Innovation Composition
AU2013355054B2 (en) 2012-12-07 2017-08-24 Chemocentryx, Inc. Diazole lactams
AR095196A1 (es) 2013-03-15 2015-09-30 Regeneron Pharma Medio de cultivo celular libre de suero
JP2018510844A (ja) * 2015-01-24 2018-04-19 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ がんマーカーおよびその使用方法
CA2973886A1 (en) * 2015-01-30 2016-08-04 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
WO2016196740A1 (en) * 2015-06-02 2016-12-08 The Rockefeller University Tri-specific antibodies for hiv therapy
CN109310677A (zh) * 2016-04-07 2019-02-05 凯莫森特里克斯股份有限公司 通过联合施用ccr1拮抗剂与pd-1抑制剂或pd-l1拮抗剂降低肿瘤负荷
EP3288086A1 (en) 2016-08-26 2018-02-28 LG Electronics Inc. Solar cell module and method for manufacturing the same
WO2018126092A1 (en) * 2016-12-29 2018-07-05 Development Center For Biotechnology Processes for preparing glycoprotein-drug conjugates
US20180325931A1 (en) 2017-01-21 2018-11-15 Ningbo Zhiming Biotechnology Co., Ltd. Use of paeoniflorin-6'-o-benzenesulfonate in treatment of sjögren's syndrome
KR102659791B1 (ko) * 2017-07-06 2024-04-23 리제너론 파마슈티칼스 인코포레이티드 당단백질을 만들기 위한 세포 배양 과정
WO2019222391A1 (en) * 2018-05-15 2019-11-21 The Board Of Trustees Of The University Of Illinois Engineered microorganisms for production of 2' fucosyllactose and l-fucose
CN110760492A (zh) * 2018-07-25 2020-02-07 复旦大学 一种岩藻糖苷酶及其在制备孟买型红细胞中的应用
JP7523789B2 (ja) * 2019-09-04 2024-07-29 独立行政法人国立病院機構 抗炎症性非フコシル化免疫グロブリン製剤及びその製造方法
US12297451B1 (en) 2019-10-25 2025-05-13 Regeneron Pharmaceuticals, Inc. Cell culture medium
TW202216771A (zh) * 2020-06-26 2022-05-01 德商拜耳廠股份有限公司 用於治療應用之ccr8抗體
US12171824B2 (en) 2020-11-06 2024-12-24 Cho Pharma, Inc. Immune composition comprising antigen and glycoengineered antibody thereof
CN113960232B (zh) * 2021-10-28 2024-02-20 苏州大学 一种基于唾液特异性岩藻糖基化结构糖谱及其检测方法和应用
CN116903738A (zh) * 2022-08-02 2023-10-20 北京绿竹生物技术股份有限公司 一种低甘露糖型抗人肿瘤坏死因子-α单抗及其用途
CN116554330B (zh) * 2023-07-04 2023-09-01 天津旷博同生生物技术有限公司 一种抗人cd24工程抗体及应用
AU2024204980A1 (en) * 2023-07-28 2025-02-13 Cho Pharma, Inc. Fucosidase mutants and the use thereof
WO2026032010A1 (en) * 2024-08-05 2026-02-12 The Hong Kong University Of Science And Technology Glycan-targeting protein aggregation therapy

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5395541A (en) * 1989-10-27 1995-03-07 The Procter & Gamble Company Cleaning composition containing a type II endoglycosidase
US6984630B1 (en) * 1998-09-21 2006-01-10 Laboratoires Goemar S.A. Endofucanases and method using same for preparing fuco-oligosaccharides from fucanes, bacterium producing endofucanases and uses of fuco-oligosaccharides for plant protection
US7090973B1 (en) 1999-04-09 2006-08-15 Oscient Pharmaceuticals Corporation Nucleic acid sequences relating to Bacteroides fragilis for diagnostics and therapeutics
WO2011005756A1 (en) * 2009-07-06 2011-01-13 Puretech Ventures, Llc Delivery of agents targeted to microbiota niches
WO2013012066A1 (ja) 2011-07-21 2013-01-24 京セラ株式会社 照明装置、イメージセンサヘッドおよびこれを備える読取装置
WO2013120066A1 (en) 2012-02-10 2013-08-15 University Of Maryland, Baltimore Chemoenzymatic glycoengineering of antibodies and fc fragments thereof
WO2015026484A1 (en) * 2013-07-26 2015-02-26 Academia Sinica Antibody-mediated anti-tumor activity induced by reishi mushroom polysaccharides

Family Cites Families (395)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
US3896111A (en) 1973-02-20 1975-07-22 Research Corp Ansa macrolides
US4151042A (en) 1977-03-31 1979-04-24 Takeda Chemical Industries, Ltd. Method for producing maytansinol and its derivatives
US4137230A (en) 1977-11-14 1979-01-30 Takeda Chemical Industries, Ltd. Method for the production of maytansinoids
USRE30985E (en) 1978-01-01 1982-06-29 Serum-free cell culture media
US4265814A (en) 1978-03-24 1981-05-05 Takeda Chemical Industries Matansinol 3-n-hexadecanoate
US4307016A (en) 1978-03-24 1981-12-22 Takeda Chemical Industries, Ltd. Demethyl maytansinoids
JPS5562090A (en) 1978-10-27 1980-05-10 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55164687A (en) 1979-06-11 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS5566585A (en) 1978-11-14 1980-05-20 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
US4256746A (en) 1978-11-14 1981-03-17 Takeda Chemical Industries Dechloromaytansinoids, their pharmaceutical compositions and method of use
JPS55102583A (en) 1979-01-31 1980-08-05 Takeda Chem Ind Ltd 20-acyloxy-20-demethylmaytansinoid compound
JPS55162791A (en) 1979-06-05 1980-12-18 Takeda Chem Ind Ltd Antibiotic c-15003pnd and its preparation
JPS55164685A (en) 1979-06-08 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
JPS55164686A (en) 1979-06-11 1980-12-22 Takeda Chem Ind Ltd Novel maytansinoid compound and its preparation
US4309428A (en) 1979-07-30 1982-01-05 Takeda Chemical Industries, Ltd. Maytansinoids
JPS5645483A (en) 1979-09-19 1981-04-25 Takeda Chem Ind Ltd C-15003phm and its preparation
EP0028683A1 (en) 1979-09-21 1981-05-20 Takeda Chemical Industries, Ltd. Antibiotic C-15003 PHO and production thereof
JPS5645485A (en) 1979-09-21 1981-04-25 Takeda Chem Ind Ltd Production of c-15003pnd
US4270537A (en) 1979-11-19 1981-06-02 Romaine Richard A Automatic hypodermic syringe
US4376110A (en) 1980-08-04 1983-03-08 Hybritech, Incorporated Immunometric assays using monoclonal antibodies
WO1982001188A1 (en) 1980-10-08 1982-04-15 Takeda Chemical Industries Ltd 4,5-deoxymaytansinoide compounds and process for preparing same
US4450254A (en) 1980-11-03 1984-05-22 Standard Oil Company Impact improvement of high nitrile resins
US4419446A (en) 1980-12-31 1983-12-06 The United States Of America As Represented By The Department Of Health And Human Services Recombinant DNA process utilizing a papilloma virus DNA as a vector
US4315929A (en) 1981-01-27 1982-02-16 The United States Of America As Represented By The Secretary Of Agriculture Method of controlling the European corn borer with trewiasine
US4313946A (en) 1981-01-27 1982-02-02 The United States Of America As Represented By The Secretary Of Agriculture Chemotherapeutically active maytansinoids from Trewia nudiflora
JPS57192389A (en) 1981-05-20 1982-11-26 Takeda Chem Ind Ltd Novel maytansinoid
US4596792A (en) 1981-09-04 1986-06-24 The Regents Of The University Of California Safe vaccine for hepatitis containing polymerized serum albumin
US4741900A (en) 1982-11-16 1988-05-03 Cytogen Corporation Antibody-metal ion complexes
US4601978A (en) 1982-11-24 1986-07-22 The Regents Of The University Of California Mammalian metallothionein promoter system
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
US4599230A (en) 1984-03-09 1986-07-08 Scripps Clinic And Research Foundation Synthetic hepatitis B virus vaccine including both T cell and B cell determinants
US4599231A (en) 1984-03-09 1986-07-08 Scripps Clinic And Research Foundation Synthetic hepatitis B virus vaccine including both T cell and B cell determinants
US4965199A (en) 1984-04-20 1990-10-23 Genentech, Inc. Preparation of functional human factor VIII in mammalian cells using methotrexate based selection
US4970198A (en) 1985-10-17 1990-11-13 American Cyanamid Company Antitumor antibiotics (LL-E33288 complex)
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4601903A (en) 1985-05-01 1986-07-22 The United States Of America As Represented By The Department Of Health And Human Services Vaccine against Neisseria meningitidis Group B serotype 2 invasive disease
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
US5567610A (en) 1986-09-04 1996-10-22 Bioinvent International Ab Method of producing human monoclonal antibodies and kit therefor
US5075109A (en) 1986-10-24 1991-12-24 Southern Research Institute Method of potentiating an immune response
US5811128A (en) 1986-10-24 1998-09-22 Southern Research Institute Method for oral or rectal delivery of microencapsulated vaccines and compositions therefor
US4886499A (en) 1986-12-18 1989-12-12 Hoffmann-La Roche Inc. Portable injection appliance
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
US5079233A (en) 1987-01-30 1992-01-07 American Cyanamid Company N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same
GB8704027D0 (en) 1987-02-20 1987-03-25 Owen Mumford Ltd Syringe needle combination
WO1988007089A1 (en) 1987-03-18 1988-09-22 Medical Research Council Altered antibodies
US4849222A (en) 1987-03-24 1989-07-18 The Procter & Gamble Company Mixtures for treating hypercholesterolemia
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4940460A (en) 1987-06-19 1990-07-10 Bioject, Inc. Patient-fillable and non-invasive hypodermic injection device assembly
US4975278A (en) 1988-02-26 1990-12-04 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
US5004697A (en) 1987-08-17 1991-04-02 Univ. Of Ca Cationized antibodies for delivery through the blood-brain barrier
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
US5053394A (en) 1988-09-21 1991-10-01 American Cyanamid Company Targeted forms of methyltrithio antitumor agents
JP2670680B2 (ja) 1988-02-24 1997-10-29 株式会社ビーエムジー 生理活性物質含有ポリ乳酸系微小球およびその製造法
US5339163A (en) 1988-03-16 1994-08-16 Canon Kabushiki Kaisha Automatic exposure control device using plural image plane detection areas
JPH01287029A (ja) 1988-05-13 1989-11-17 Mect Corp 新規抗ウィルス剤
AU632065B2 (en) 1988-09-23 1992-12-17 Novartis Vaccines And Diagnostics, Inc. Cell culture medium for enhanced cell growth, culture longevity and product expression
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
FR2638359A1 (fr) 1988-11-03 1990-05-04 Tino Dalto Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau
US5175384A (en) 1988-12-05 1992-12-29 Genpharm International Transgenic mice depleted in mature t-cells and methods for making transgenic mice
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
ES2096590T3 (es) 1989-06-29 1997-03-16 Medarex Inc Reactivos biespecificos para la terapia del sida.
US5690938A (en) 1989-07-07 1997-11-25 Oravax, Inc. Oral immunization with multiple particulate antigen delivery system
US5518725A (en) 1989-09-25 1996-05-21 University Of Utah Research Foundation Vaccine compositions and method for induction of mucosal immune response via systemic vaccination
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
EP1690934A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US5061620A (en) 1990-03-30 1991-10-29 Systemix, Inc. Human hematopoietic stem cell
US5112596A (en) 1990-04-23 1992-05-12 Alkermes, Inc. Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability
US5268164A (en) 1990-04-23 1993-12-07 Alkermes, Inc. Increasing blood-brain barrier permeability with permeabilizer peptides
CZ288492B6 (en) 1990-04-24 2001-06-13 Biota Scient Management Derivatives of alpha-D-neuraminic acid, process of their preparation, their use and pharmaceutical preparations based thereon
US5643577A (en) 1990-04-24 1997-07-01 The University Of Newcastle Research Associates Limited Oral vaccine comprising antigen surface-associated with red blood cells
US5229275A (en) 1990-04-26 1993-07-20 Akzo N.V. In-vitro method for producing antigen-specific human monoclonal antibodies
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
DE69132709T2 (de) 1990-06-29 2002-06-20 Large Scale Biology Corp., Vacaville Melaninproduktion durch transformierte mikroorganismen
US5190521A (en) 1990-08-22 1993-03-02 Tecnol Medical Products, Inc. Apparatus and method for raising a skin wheal and anesthetizing skin
ATE300615T1 (de) 1990-08-29 2005-08-15 Genpharm Int Transgene mäuse fähig zur produktion heterologer antikörper
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5714374A (en) 1990-09-12 1998-02-03 Rutgers University Chimeric rhinoviruses
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
WO1992006691A1 (en) 1990-10-19 1992-04-30 Biota Scientific Management Pty. Ltd. Anti-viral compounds that bind the active site of influenza neuramidase and display in vivo activity against orthomyxovirus and paramyxovirus
US5508192A (en) 1990-11-09 1996-04-16 Board Of Regents, The University Of Texas System Bacterial host strains for producing proteolytically sensitive polypeptides
US5264365A (en) 1990-11-09 1993-11-23 Board Of Regents, The University Of Texas System Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides
CA2405246A1 (en) 1990-12-03 1992-06-11 Genentech, Inc. Enrichment method for variant proteins with alterred binding properties
US5527288A (en) 1990-12-13 1996-06-18 Elan Medical Technologies Limited Intradermal drug delivery device and method for intradermal delivery of drugs
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
DE69222303T2 (de) 1991-04-30 1998-01-22 Eukarion Inc Kationisierte antikörper gegen intrazelluläre eiweisse
EP1400536A1 (en) 1991-06-14 2004-03-24 Genentech Inc. Method for making humanized antibodies
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
GB9118204D0 (en) 1991-08-23 1991-10-09 Weston Terence E Needle-less injector
SE9102652D0 (sv) 1991-09-13 1991-09-13 Kabi Pharmacia Ab Injection needle arrangement
WO1993006217A1 (en) 1991-09-19 1993-04-01 Genentech, Inc. EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES
ES2136092T3 (es) 1991-09-23 1999-11-16 Medical Res Council Procedimientos para la produccion de anticuerpos humanizados.
AU665025B2 (en) 1991-09-23 1995-12-14 Cambridge Antibody Technology Limited Production of chimeric antibodies - a combinatorial approach
US5362852A (en) 1991-09-27 1994-11-08 Pfizer Inc. Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties
FI941572L (fi) 1991-10-07 1994-05-27 Oncologix Inc Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä
US5288502A (en) 1991-10-16 1994-02-22 The University Of Texas System Preparation and uses of multi-phase microspheres
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
CA2122719A1 (en) 1991-11-19 1993-05-27 Jack M. Gwaltney, Jr. Combined virustatic antimediator (covam) treatment of common colds
JPH0826057B2 (ja) 1992-01-16 1996-03-13 株式会社ディ・ディ・エス研究所 シアル酸オリゴ糖誘導体及び微粒子キャリヤー
US5667988A (en) 1992-01-27 1997-09-16 The Scripps Research Institute Methods for producing antibody libraries using universal or randomized immunoglobulin light chains
AU675929B2 (en) 1992-02-06 1997-02-27 Curis, Inc. Biosynthetic binding protein for cancer marker
US5328483A (en) 1992-02-27 1994-07-12 Jacoby Richard M Intradermal injection device with medication and needle guard
US5733743A (en) 1992-03-24 1998-03-31 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
US5326856A (en) 1992-04-09 1994-07-05 Cytogen Corporation Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal binding
ZA932522B (en) 1992-04-10 1993-12-20 Res Dev Foundation Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens
JP2904647B2 (ja) 1992-06-12 1999-06-14 株式会社蛋白工学研究所 ５−ブロム−４−クロロインド−３−イル−２−シアル酸の製造方法
DE69334095T2 (de) 1992-07-17 2007-04-12 Dana-Farber Cancer Institute, Boston Verfahren zur intrazellulären Bindung von zielgerichteten Molekülen
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
ATE191853T1 (de) 1992-07-27 2000-05-15 Us Health Zielgerichte liposome zur blut-hirne schranke
EP0656064B1 (en) 1992-08-17 1997-03-05 Genentech, Inc. Bispecific immunoadhesins
US5569189A (en) 1992-09-28 1996-10-29 Equidyne Systems, Inc. hypodermic jet injector
EP0666268B1 (en) 1992-10-22 2000-04-19 Kirin Beer Kabushiki Kaisha Novel sphingoglycolipid and use thereof
US5334144A (en) 1992-10-30 1994-08-02 Becton, Dickinson And Company Single use disposable needleless injector
US5807722A (en) 1992-10-30 1998-09-15 Bioengineering Resources, Inc. Biological production of acetic acid from waste gases with Clostridium ljungdahlii
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
MD1367C2 (ro) 1992-11-13 2000-11-30 Idec Pharmaceuticals Corporation Metode de tratament al limfomului celulelor B, anticorpi anti-CD20, hibridom.
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
JP3523285B2 (ja) 1993-01-22 2004-04-26 雪印乳業株式会社 糖分解酵素の製造法
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
US5374541A (en) 1993-05-04 1994-12-20 The Scripps Research Institute Combined use of β-galactosidase and sialyltransferase coupled with in situ regeneration of CMP-sialic acid for one pot synthesis of oligosaccharides
US20020037517A1 (en) 1993-05-28 2002-03-28 Hutchens T. William Methods for sequencing biopolymers
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
WO1995011010A1 (en) 1993-10-22 1995-04-27 Genentech, Inc. Methods and compositions for microencapsulation of antigens for use as vaccines
US5369017A (en) 1994-02-04 1994-11-29 The Scripps Research Institute Process for solid phase glycopeptide synthesis
WO1995023157A1 (en) 1994-02-25 1995-08-31 E.I. Du Pont De Nemours And Company 4-n-substituted sialic acids and their sialosides
WO1995024176A1 (en) 1994-03-07 1995-09-14 Bioject, Inc. Ampule filling device
US5466220A (en) 1994-03-08 1995-11-14 Bioject, Inc. Drug vial mixing and transfer device
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
US5622701A (en) 1994-06-14 1997-04-22 Protein Design Labs, Inc. Cross-reacting monoclonal antibodies specific for E- and P-selectin
ES2251723T3 (es) 1994-08-12 2006-05-01 Immunomedics, Inc. Inmunoconjugados y anticuerpos humanizados especificos para linfoma de celulas b y celulas de leucemia.
US5639635A (en) 1994-11-03 1997-06-17 Genentech, Inc. Process for bacterial production of polypeptides
JPH10511085A (ja) 1994-12-02 1998-10-27 カイロン コーポレイション 二重特異性抗体を用いる免疫応答を促進する方法
US5663149A (en) 1994-12-13 1997-09-02 Arizona Board Of Regents Acting On Behalf Of Arizona State University Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides
US5599302A (en) 1995-01-09 1997-02-04 Medi-Ject Corporation Medical injection system and method, gas spring thereof and launching device using gas spring
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US6673533B1 (en) 1995-03-10 2004-01-06 Meso Scale Technologies, Llc. Multi-array multi-specific electrochemiluminescence testing
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
WO1996036436A1 (en) 1995-04-25 1996-11-21 Irori Remotely programmable matrices with memories and uses thereof
CA2219361C (en) 1995-04-27 2012-02-28 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP0823941A4 (en) 1995-04-28 2001-09-19 Abgenix Inc HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES
US5730723A (en) 1995-10-10 1998-03-24 Visionary Medical Products Corporation, Inc. Gas pressured needle-less injection device and method
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
US6265150B1 (en) 1995-06-07 2001-07-24 Becton Dickinson & Company Phage antibodies
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5837234A (en) 1995-06-07 1998-11-17 Cytotherapeutics, Inc. Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane
CA2227871A1 (en) 1995-07-26 1997-02-13 Maxim Pharmaceuticals, Inc. Mucosal delivery of polynucleotides
DE19544393A1 (de) 1995-11-15 1997-05-22 Hoechst Schering Agrevo Gmbh Synergistische herbizide Mischungen
US5893397A (en) 1996-01-12 1999-04-13 Bioject Inc. Medication vial/syringe liquid-transfer apparatus
WO1997038123A1 (en) 1996-04-05 1997-10-16 Board Of Regents, The University Of Texas System Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells
GB9607549D0 (en) 1996-04-11 1996-06-12 Weston Medical Ltd Spring-powered dispensing device
US5922845A (en) 1996-07-11 1999-07-13 Medarex, Inc. Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies
US6340702B1 (en) 1996-07-22 2002-01-22 Sankyo Company, Limited Neuraminic acid derivatives, their preparation and their medical use
US6506564B1 (en) 1996-07-29 2003-01-14 Nanosphere, Inc. Nanoparticles having oligonucleotides attached thereto and uses therefor
NZ335368A (en) 1996-11-14 2001-08-31 Biota Scient Management Macromolecular compound with one or more neuraminidase binders, binds to the active site of influenza virus neuraminidase
EP1500329B1 (en) 1996-12-03 2012-03-21 Amgen Fremont Inc. Human antibodies that specifically bind human TNF alpha
TW555562B (en) 1996-12-27 2003-10-01 Kirin Brewery Method for activation of human antigen-presenting cells, activated human antigen-presenting cells and use thereof
CA2284729A1 (en) 1997-04-18 1998-10-29 Novartis Ag Neoglycoproteins
US5993412A (en) 1997-05-19 1999-11-30 Bioject, Inc. Injection apparatus
US6083715A (en) 1997-06-09 2000-07-04 Board Of Regents, The University Of Texas System Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells
JPH1135593A (ja) 1997-07-18 1999-02-09 Daikin Ind Ltd ２−フルオロフコシル−ｎ−アロイルグルコサミン誘導体及びその中間物、並びにそれらの製造方法
TW477783B (en) 1997-12-12 2002-03-01 Gilead Sciences Inc Novel compounds useful as neuraminidase inhibitors and pharmaceutical compositions containing same
IT1298087B1 (it) 1998-01-08 1999-12-20 Fiderm S R L Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni
CA2324648C (en) 1998-03-27 2013-02-26 Prolume, Ltd. Luciferases, fluorescent proteins, nucleic acids encoding the luciferases and fluorescent proteins and the use thereof in diagnostics, high throughput screening and novelty items
ES2292236T3 (es) 1998-04-02 2008-03-01 Genentech, Inc. Variantes de anticuerpos y sus fragmentos.
ES2434961T5 (es) 1998-04-20 2018-01-18 Roche Glycart Ag Ingeniería de glicosilación de anticuerpos para mejorar la citotoxicidad celular dependiente del anticuerpo
US6455571B1 (en) 1998-04-23 2002-09-24 Abbott Laboratories Inhibitors of neuraminidases
PT1308456E (pt) 1998-05-06 2007-12-03 Genentech Inc Purificação de anticorpos por cromatografia de permuta iónica
US6528286B1 (en) 1998-05-29 2003-03-04 Genentech, Inc. Mammalian cell culture process for producing glycoproteins
JP3773153B2 (ja) 1998-05-29 2006-05-10 独立行政法人理化学研究所 シアル酸誘導体
EP2306195A3 (en) 1998-09-18 2012-04-25 Massachusetts Institute of Technology Biological applications of semiconductor nanocrystals
US6696304B1 (en) 1999-02-24 2004-02-24 Luminex Corporation Particulate solid phase immobilized protein quantitation
AUPP913999A0 (en) 1999-03-12 1999-04-01 Biota Scientific Management Pty Ltd Novel chemical compounds and their use
US7854934B2 (en) 1999-08-20 2010-12-21 Sloan-Kettering Institute For Cancer Research Glycoconjugates, glycoamino acids, intermediates thereto, and uses thereof
US6824780B1 (en) 1999-10-29 2004-11-30 Genentech, Inc. Anti-tumor antibody compositions and methods of use
AUPQ422399A0 (en) 1999-11-24 1999-12-16 University Of New South Wales, The Method of screening transformed or transfected cells
US6727356B1 (en) 1999-12-08 2004-04-27 Epoch Pharmaceuticals, Inc. Fluorescent quenching detection reagents and methods
US20020098513A1 (en) 2000-02-17 2002-07-25 Glycominds Ltd. Combinatorial complex carbohydrate libraries and methods for the manufacture and uses thereof
US7019129B1 (en) 2000-05-09 2006-03-28 Biosearch Technologies, Inc. Dark quenchers for donor-acceptor energy transfer
US7863020B2 (en) 2000-06-28 2011-01-04 Glycofi, Inc. Production of sialylated N-glycans in lower eukaryotes
US6514221B2 (en) 2000-07-27 2003-02-04 Brigham And Women's Hospital, Inc. Blood-brain barrier opening
US20020065259A1 (en) 2000-08-30 2002-05-30 Schatzberg Alan F. Glucocorticoid blocking agents for increasing blood-brain barrier permeability
AUPR001000A0 (en) 2000-09-08 2000-10-05 Biota Scientific Management Pty Ltd Novel chemical compounds and their use
US7034036B2 (en) 2000-10-30 2006-04-25 Pain Therapeutics, Inc. Inhibitors of ABC drug transporters at the blood-brain barrier
US20030083299A1 (en) 2000-11-04 2003-05-01 Ferguson Ian A. Non-invasive delivery of polypeptides through the blood-brain barrier
JP2002153272A (ja) 2000-11-24 2002-05-28 Inst Of Physical & Chemical Res 生体分子マイクロアレイ
US7754208B2 (en) 2001-01-17 2010-07-13 Trubion Pharmaceuticals, Inc. Binding domain-immunoglobulin fusion proteins
US20030104402A1 (en) 2001-01-23 2003-06-05 University Of Rochester Methods of producing or identifying intrabodies in eukaryotic cells
US6884869B2 (en) 2001-04-30 2005-04-26 Seattle Genetics, Inc. Pentapeptide compounds and uses related thereto
DE10121982B4 (de) 2001-05-05 2008-01-24 Lts Lohmann Therapie-Systeme Ag Nanopartikel aus Protein mit gekoppeltem Apolipoprotein E zur Überwindung der Blut-Hirn-Schranke und Verfahren zu ihrer Herstellung
JP2002371087A (ja) 2001-06-15 2002-12-26 Mitsubishi Chemicals Corp 有機ホスホン酸
JP4202250B2 (ja) 2001-07-25 2008-12-24 バイオマリン ファーマシューティカル インコーポレイテッド 血液脳関門輸送を調節するための組成物および方法
CN1561389A (zh) 2001-07-25 2005-01-05 纽约大学 糖基神经酰胺作为用于抗传染病和癌症的疫苗的佐剂的用途
CA2454587C (en) 2001-07-25 2012-11-13 Protein Design Labs, Inc. Stable lyophilized pharmaceutical formulation of igg antibodies
EP2180044A1 (en) 2001-08-03 2010-04-28 GlycArt Biotechnology AG Antibody glycosylation variants having increased anti-body-dependent cellular cytotoxicity
EP2042196B1 (en) * 2001-10-10 2016-07-13 ratiopharm GmbH Remodelling and glycoconjugation of Granulocyte Colony Stimulating Factor (G-CSF)
JP4763237B2 (ja) 2001-10-19 2011-08-31 キャボット コーポレイション 基板上に導電性電子部品を製造する方法
AUPR879601A0 (en) 2001-11-09 2001-12-06 Biota Scientific Management Pty Ltd Novel chemical compounds and their use
US20040023295A1 (en) 2001-11-21 2004-02-05 Carol Hamilton Methods and systems for analyzing complex biological systems
KR101033196B1 (ko) 2002-02-14 2011-05-09 이뮤노메딕스, 인코오포레이티드 항-ｃｄ20 항체 및 그 융합 단백질 및 이들의 이용방법
US20030162695A1 (en) 2002-02-27 2003-08-28 Schatzberg Alan F. Glucocorticoid blocking agents for increasing blood-brain barrier permeability
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
AU2003219277A1 (en) 2002-03-14 2003-09-29 Medical Research Council Intracellular antibodies
MXPA04011249A (es) 2002-05-14 2005-06-06 Chiron Srl Vacunas mucosales con adyuvante de quitosano y antigenos meningococicos.
US7157433B2 (en) 2002-07-08 2007-01-02 Glaxosmithkline Istrazivacki Centar Zagreb Compounds, compositions as carriers for steroid/nonsteroid anti-inflammatory; antienoplastic and antiviral active molecules
US20080070324A1 (en) 2002-07-15 2008-03-20 Floyd Alton D Quantity control device for microscope slide staining assays
EP1391213A1 (en) 2002-08-21 2004-02-25 Boehringer Ingelheim International GmbH Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents
US20040062682A1 (en) 2002-09-30 2004-04-01 Rakow Neal Anthony Colorimetric sensor
CN101928344B (zh) 2002-10-17 2014-08-13 根马布股份公司 抗cd20的人单克隆抗体
CN101284136A (zh) 2002-12-03 2008-10-15 布朗歇特洛克菲勒神经科学研究所 传输物质穿过血脑屏障的人工低密度脂蛋白载体
EP3263596A1 (en) 2002-12-16 2018-01-03 Genentech, Inc. Immunoglobulin variants and uses thereof
JP2006524039A (ja) 2003-01-09 2006-10-26 マクロジェニクス，インコーポレーテッド 変異型Ｆｃ領域を含む抗体の同定および作製ならびにその利用法
CN103540600B (zh) * 2003-01-22 2017-12-01 罗氏格黎卡特股份公司 融合构建体及其用来生产Fc受体结合亲和性和效应子功能提高的抗体的用途
US8088387B2 (en) 2003-10-10 2012-01-03 Immunogen Inc. Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates
AR044388A1 (es) 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
US20040259142A1 (en) 2003-06-04 2004-12-23 Imperial College Innovations Limited Products and methods
EP1639090A4 (en) 2003-06-09 2008-04-16 Univ Michigan COMPOSITIONS AND METHODS OF TREATMENT AND DIAGNOSIS OF CANCER
JP4148844B2 (ja) 2003-06-11 2008-09-10 ソニー・エリクソン・モバイルコミュニケーションズ株式会社 情報端末装置及び音声付画像ファイルの出力方法
US7803376B2 (en) * 2003-07-24 2010-09-28 Innate Pharma S.A. Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds
EP1654004A2 (en) 2003-08-08 2006-05-10 Novo Nordisk A/S Synthesis and application of new structural well defined branched polymers as conjugating agents for peptides
US20050089473A1 (en) 2003-09-10 2005-04-28 Cedars-Sinai Medical Center Potassium channel mediated delivery of agents through the blood-brain barrier
JP2007505697A (ja) 2003-09-15 2007-03-15 ウィックストローム、エリック シリル化治療剤を結合したインプラント
JP2007522094A (ja) 2003-09-22 2007-08-09 アシドフィル エルエルシー 小分子組成物、及びその組成物を使用して薬物効率を高めるための方法
US7019288B2 (en) 2003-09-30 2006-03-28 Sequenom, Inc. Methods of making substrates for mass spectrometry analysis and related devices
US20050221337A1 (en) 2003-10-02 2005-10-06 Massachusetts Institute Of Technology Microarrays and microspheres comprising oligosaccharides, complex carbohydrates or glycoproteins
ES2672640T3 (es) 2003-11-05 2018-06-15 Roche Glycart Ag Moléculas de unión a antígeno con afinidad de unión a receptores Fc y función efectora incrementadas
US7498298B2 (en) 2003-11-06 2009-03-03 Seattle Genetics, Inc. Monomethylvaline compounds capable of conjugation to ligands
US20050255491A1 (en) 2003-11-13 2005-11-17 Lee Frank D Small molecule and peptide arrays and uses thereof
EP1723422A2 (en) 2004-03-05 2006-11-22 The Scripps Research Institute High throughput glycan microarrays
US20050221397A1 (en) 2004-03-30 2005-10-06 Northern Advancement Center For Science & Technology RM2 antigen (beta1,4-GalNAc-disialyl-Lc4) as prostate cancer-associated antigen
WO2005103081A2 (en) 2004-04-20 2005-11-03 Genmab A/S Human monoclonal antibodies against cd20
ITMI20040928A1 (it) 2004-05-07 2004-08-07 Uni Di Bologna Dipartiment O D Procedura per la preparazione di coniugati della doxorubicina con l'albumina umana lattosaminata
AU2005258281A1 (en) 2004-06-24 2006-01-05 The Scripps Research Institute Arrays with cleavable linkers
KR20140032004A (ko) 2004-07-22 2014-03-13 제넨테크, 인크. Ｈｅｒ２ 항체 조성물
US8022043B2 (en) 2004-08-27 2011-09-20 Albert Einstein College Of Medicine Of Yeshiva University Ceramide derivatives as modulators of immunity and autoimmunity
WO2006060171A2 (en) 2004-11-16 2006-06-08 Board Of Regents, The University Of Texas System Methods and compositions related to phage-nanoparticle assemblies
WO2006055925A2 (en) 2004-11-19 2006-05-26 Swiss Federal Institute Of Technology Microarrays for analyte detection
WO2006064983A1 (en) 2004-12-14 2006-06-22 Korea Research Institute Of Bioscience And Biotechnology Monoclonal antibody specific human embryonic stem cell
US7923013B2 (en) 2004-12-28 2011-04-12 The Rockefeller University Glycolipids and analogues thereof as antigens for NKT cells
JP5090928B2 (ja) 2004-12-28 2012-12-05 ザ ロックフェラー ユニバーシティ Ｎｋｔ細胞に対する抗原としての糖脂質及びその類似体
US8551483B2 (en) 2005-01-06 2013-10-08 Innate Pharma S.A.S. Methods of treating viral infections by administering KIR2DL-binding antibodies
US7837990B2 (en) 2005-03-28 2010-11-23 The Rockefeller University In vivo expanded NKT cells and methods of use thereof
EP1865058B1 (en) 2005-03-31 2011-01-12 Biomedics Inc. Anti-cd-20 monoclonal antibody
US20060252096A1 (en) 2005-04-26 2006-11-09 Glycofi, Inc. Single chain antibody with cleavable linker
MX2007014673A (es) 2005-05-24 2008-04-08 Avestha Gengraine Tech Pvt Ltd Metodo para la produccion de un anticuerpo monoclonal para cd20 para el tratamiento de linfoma de celular b.
KR20080031001A (ko) 2005-06-02 2008-04-07 아스트라제네카 아베 Ｃｄ20에 대한 항체 및 그의 용도
DK1896071T3 (en) * 2005-06-30 2015-05-26 Janssen Biotech Inc Methods and compositions with increased therapeutic activity
JP2007036104A (ja) 2005-07-29 2007-02-08 Nec Electronics Corp 半導体装置およびその製造方法
WO2007028106A2 (en) * 2005-08-31 2007-03-08 Centocor, Inc. Host cell lines for production of antibody constant region with enhanced effector function
JP5129149B2 (ja) 2005-10-31 2013-01-23 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン 癌を処置および診断するための組成物および方法
MY149159A (en) 2005-11-15 2013-07-31 Hoffmann La Roche Method for treating joint damage
US7781203B2 (en) 2005-12-29 2010-08-24 Corning Incorporated Supports for assaying analytes and methods of making and using thereof
US20090060921A1 (en) * 2006-01-17 2009-03-05 Biolex Therapeutics, Inc. Glycan-optimized anti-cd20 antibodies
CA2647632C (en) 2006-03-27 2017-06-27 University Of Maryland Biotechnology Institute Glycoprotein synthesis and remodeling by enzymatic transglycosylation
MX2008014529A (es) 2006-05-18 2009-01-28 Veterinaermedizinische Uni Wie Metodo de deteccion para virus de influenza.
CA2655246A1 (en) 2006-06-09 2007-12-21 University Of Maryland, Baltimore Glycosylation engineered antibody therapy
WO2008006373A1 (en) 2006-07-12 2008-01-17 Merck Patent Gmbh Solid-phase detection of terminal monosaccharides cleaved from glycosylated substrates
JP2008025989A (ja) 2006-07-15 2008-02-07 Keio Gijuku 局在表面プラズモン共鳴法と質量分析法によるリガンドの分析方法及びそのためのセンサー素子
JP2010501161A (ja) 2006-08-18 2010-01-21 オンコセラピー・サイエンス株式会社 Ｒｅｇ４またはｋｉａａ０１０１を過剰発現している癌の治療または予防
US8444971B2 (en) 2006-11-27 2013-05-21 Diadexus, Inc. OVR110 antibody compositions and methods of use
US8765390B2 (en) 2006-12-08 2014-07-01 The Board Of Trustees Of The Leland Stanford Junior University Identification and isolation of squamous carcinoma stem cells
US9239329B2 (en) 2006-12-18 2016-01-19 Japan Science And Technology Agency Method of measuring interaction between biomaterial and sugar chain, method of evaluating biomaterial in sugar chain selectivity, method of screening biomaterial, method of patterning biomaterials, and kits for performing these methods
AU2008206884B2 (en) 2007-01-18 2012-07-05 Glykos Finland Oy Novel methods and reagents directed to production of cells
JP2010516241A (ja) 2007-01-18 2010-05-20 スオメン プナイネン リスティ，ヴェリパルベル 新規の特異的細胞結合剤
KR101523698B1 (ko) 2007-01-22 2015-05-29 마크로제닉스 웨스트 인코퍼레이티드 사람 암 줄기세포
WO2008103824A1 (en) 2007-02-23 2008-08-28 Chinese Academy Of Inspection And Quarantine (Caiq) Sensitivity-enhanced dot-antibody linked immunogold assay for virus detection
US20080220988A1 (en) 2007-03-07 2008-09-11 Ada Technologies, Inc. Preparing carbohydrate microarrays and conjugated nanoparticles
DK2123271T3 (da) 2007-03-07 2012-01-23 Daiichi Sankyo Co Ltd Lægemiddel til behandling af influenza
US7943330B2 (en) 2007-03-23 2011-05-17 Academia Sinica Tailored glycoproteomic methods for the sequencing, mapping and identification of cellular glycoproteins
US7960139B2 (en) 2007-03-23 2011-06-14 Academia Sinica Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells
DK2308514T3 (da) 2007-03-23 2013-09-02 To Bbb Holding B V Konjugater til målrettet lægemiddeltransport gennem blod-hjerne barrieren
JP2010523724A (ja) 2007-04-13 2010-07-15 アカデミア シニカ α−ガラクトシルセラミド類似体およびそれらの免疫療法剤としての使用
CA2685015A1 (en) 2007-04-23 2008-11-06 Schering Corporation Anti-mdl-1 antibodies
US8082480B2 (en) 2007-06-27 2011-12-20 Presagis Distributed checksum computation
AU2008275649B2 (en) 2007-07-12 2013-09-05 Sangamo Therapeutics, Inc. Methods and compositions for inactivating alpha 1,6 fucosyltransferase (FUT 8) gene expression
EP2022848A1 (en) 2007-08-10 2009-02-11 Hubrecht Institut A method for identifying, expanding, and removing adult stem cells and cancer stem cells
US20110306049A1 (en) 2007-08-24 2011-12-15 Tokyo Institute Of Technology Method for detecting gynecologic cancer
JP5509080B2 (ja) 2007-08-31 2014-06-04 アカデミア シニカ 抗インフルエンザ活性を有するオセルタミビル含有ホスホネートコンジナーの合成
FR2921387B1 (fr) 2007-09-26 2012-04-20 Sanofi Pasteur Procede de production du virus de la grippe
US8647626B2 (en) 2007-10-02 2014-02-11 Avaxia Biologics, Incorporated Compositions comprising TNF-specific antibodies for oral delivery
US20090123439A1 (en) 2007-11-09 2009-05-14 The Jackson Laboratory Diagnostic and prognosis methods for cancer stem cells
EP2225276B1 (en) 2007-12-31 2014-04-23 Bayer Intellectual Property GmbH Antibodies to tnf alpha
BRPI0908968A8 (pt) 2008-03-21 2016-06-28 Danisco Us Inc composição enriquecidas com hemicelulase para potencializar a hidrólise de biomassa
EP2272854B1 (en) 2008-03-25 2015-08-05 Riken Novel glycolipid and use thereof
JP5792614B2 (ja) 2008-04-09 2015-10-14 ベクトン・ディキンソン・アンド・カンパニーＢｅｃｔｏｎ， Ｄｉｃｋｉｎｓｏｎ Ａｎｄ Ｃｏｍｐａｎｙ 被覆ナノ粒子を使用した高感度免疫学的検定
US8383554B2 (en) 2008-04-14 2013-02-26 Academia Sinica Quantitative microarray of intact glycolipid CD1d interaction and correlation with cell-based cytokine production
WO2009132130A2 (en) * 2008-04-22 2009-10-29 The Rockefeller University Methods of identifying anti-inflammatory compounds
US8906832B2 (en) 2008-04-30 2014-12-09 Academia Sinica Quantitative analysis of carbohydrate-protein interactions using glycan microarrays: determination of surface and solution dissociation constants
CN102036658A (zh) 2008-05-23 2011-04-27 香港大学 治疗流感的联合疗法
WO2009154964A2 (en) * 2008-05-30 2009-12-23 Glycome Technologies Inc. Methods for structural analysis of glycans
CN102065868A (zh) 2008-06-16 2011-05-18 中央研究院 诱发对于Globo H及SSEA3的特异免疫反应的组合物以及其在癌症治疗中的用途
ES2477549T3 (es) 2008-06-16 2014-07-17 Academia Sinica Diagnóstico del cáncer según la concentración de anticuerpos contra Globo H y sus fragmentos
JP2010014691A (ja) 2008-06-20 2010-01-21 Igaku Seibutsugaku Kenkyusho:Kk 腹水中のメソテリン及び／又は巨核球増強因子を検出するための方法、キット、試薬及び装置
US20100003674A1 (en) 2008-07-03 2010-01-07 Cope Frederick O Adult stem cells, molecular signatures, and applications in the evaluation, diagnosis, and therapy of mammalian conditions
US7928077B2 (en) 2008-07-11 2011-04-19 Academia Sinica Alpha-galactosyl ceramide analogs and their use as immunotherapies
JP5986745B2 (ja) 2008-07-15 2016-09-06 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ Ｐｔｆｅ様のアルミニウム・コート・ガラススライド上のグリカンアレイおよび関連する方法
US20100022916A1 (en) 2008-07-24 2010-01-28 Javanbakhsh Esfandiari Method and Apparatus for Collecting and Preparing Biological Samples for Testing
GB0816679D0 (en) 2008-09-11 2008-10-22 Univ Bath Compounds for treating viral infections
WO2010036443A1 (en) 2008-09-26 2010-04-01 Eureka Therapeutics, Inc. Cell lines and proteins with variant glycosylation pattern
WO2010037402A1 (en) * 2008-10-02 2010-04-08 Dako Denmark A/S Molecular vaccines for infectious disease
CN102203290B (zh) 2008-10-27 2015-05-06 北海道公立大学法人札幌医科大学 肿瘤干细胞分子标记
KR20110097772A (ko) * 2008-11-17 2011-08-31 제넨테크, 인크. 생리적 조건하에 거대분자의 응집을 감소시키는 방법 및 제제
CA2751730A1 (en) * 2009-02-25 2010-09-02 Merck Sharp & Dohme Corp. Metabolic engineering of a galactose assimilation pathway in the glycoengineered yeast pichia pastoris
DK2411528T3 (en) 2009-03-27 2015-12-14 Academia Sinica ALFA-SELECTIVE SIALYLPHOSPHATDONORER MAKING SIALOSIDER AND sialoside arrays FOR DETECTION OF INFLUENZA
MX2011011772A (es) * 2009-05-04 2012-02-08 Abbott Biotech Ltd Formulaicones estables de anticuerpos humanos anti-tnf-alfa con alta concentracion de proteina.
AU2010273118B2 (en) 2009-07-15 2015-10-29 The University Of British Columbia 2,3-fluorinated glycosides as neuraminidase inhibitors and their use as anti-virals
US20120171201A1 (en) 2009-07-22 2012-07-05 Enzon Pharmaceuticals, Inc. Methods of treating her2 positive cancer with her2 receptor antagonist in combination with multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin
US20120172329A1 (en) 2009-09-14 2012-07-05 Thailand Excellence Center For Tissue Engineering Phytochemical compositions including xanthones for anti-inflammatory, anti-cytokine storm, and other uses
US10087236B2 (en) * 2009-12-02 2018-10-02 Academia Sinica Methods for modifying human antibodies by glycan engineering
JPWO2011074621A1 (ja) 2009-12-18 2013-04-25 株式会社医学生物学研究所 メソセリン（ｍｓｌｎ）に対する抗体及びその用途
EP2347769A1 (en) 2010-01-20 2011-07-27 Glycotope GmbH Cancer stem cell markers and uses thereof
WO2011100538A1 (en) 2010-02-11 2011-08-18 Alexion Pharmaceuticals, Inc. Therapeutic methods using an ti-cd200 antibodies
BR112012020882A2 (pt) 2010-02-24 2015-11-03 Merck Sharp & Dohme métodos para produzir uma glicoproteína heteróloga e para produzir uma composição de glicoproteína, célula hospedeira, composição de glicoproteína, e, uso da pichia pastoris recombinante.
SG183542A1 (en) 2010-03-12 2012-10-30 Immunogen Inc Cd37-binding molecules and immunoconjugates thereof
US10338069B2 (en) 2010-04-12 2019-07-02 Academia Sinica Glycan arrays for high throughput screening of viruses
CA2796464C (en) 2010-04-16 2021-08-03 Immune Disease Institute, Inc. Sustained polypeptide expression from synthetic, modified rnas and uses thereof
CN103068378B (zh) 2010-05-10 2016-07-06 中央研究院 具有抗流感活性的扎那米韦膦酸酯同类物及其制备方法
WO2011145957A1 (en) 2010-05-20 2011-11-24 Auckland Uniservices Limited Agents and methods for detection and/or imaging of hypoxia
CA2799595C (en) * 2010-05-27 2022-08-16 Merck Sharp & Dohme Corp. Method for preparing antibodies having improved properties
PE20140229A1 (es) * 2010-08-26 2014-03-27 Abbvie Inc Inmunoglobulinas con dominio variable dual y usos de las mismas
GB201015569D0 (en) 2010-09-16 2010-10-27 Medical Res Council Blood assay for prions
WO2012082635A1 (en) 2010-12-13 2012-06-21 Ancora Pharmaceuticals, Inc. Synthetic oligosaccharide group a streptococcus
HK1197068A1 (en) 2011-01-05 2015-01-02 台湾大学 Methods for preparation of glycosphingolipids and uses thereof
US20130331381A1 (en) 2011-02-28 2013-12-12 Mcmaster University Treatment of Cancer WIth Dopamine Receptor Antagonists
US10851174B2 (en) 2011-03-03 2020-12-01 University Of Maryland, Baltimore Core fucosylated glycopeptides and glycoproteins: chemoenzymatic synthesis and uses thereof
US9328170B2 (en) 2011-05-25 2016-05-03 Merck Sharp & Dohme Corp. Method for preparing Fc containing polypeptides having improved properties
HRP20190714T1 (hr) 2011-07-18 2019-06-14 Institute For Research In Biomedicine Neutralizirajuća protutijela anti-influenca a virusa i njihova uporaba
AU2012295802B2 (en) 2011-08-12 2017-03-30 Nissan Chemical Industries, Ltd. Tricyclic heterocyclic compounds and JAK inhibitors
US20140286946A1 (en) * 2011-10-31 2014-09-25 Merck Sharp & Dohme Corp. Method for preparing antibodies having improved properties
EP2780463A4 (en) 2011-11-18 2015-07-01 Merck Sharp & Dohme FC-CONTAINING POLYPEPTIDES WITH INCREASED INFLAMMATORY FEATURES AND INCREASED FCRN BINDING
EP2604281B1 (en) 2011-12-14 2014-07-30 Centre National de la Recherche Scientifique (CNRS) Clicked somatostatin conjugated analogs for biological applications
WO2013106937A1 (en) 2012-01-19 2013-07-25 The University Of British Columbia 3' equatorial-fluorine-substituted neuraminidase inhibitor compounds, compositions and methods for the use thereof as anti-virals
GB201201314D0 (en) * 2012-01-26 2012-03-07 Isis Innovation Composition
WO2013130603A1 (en) 2012-02-27 2013-09-06 Board Of Regents, The University Of Texas System Ganglioside gd2 as a marker and target on cancer stem cells
BR112014024494A2 (pt) 2012-04-02 2017-08-08 Merrimack Pharmaceuticals Inc dosagem e administração de anticorpos anti-igf-1r e anti-erbb3 monoespecíficos e biespecíficos
WO2013151649A1 (en) 2012-04-04 2013-10-10 Sialix Inc Glycan-interacting compounds
US10130714B2 (en) 2012-04-14 2018-11-20 Academia Sinica Enhanced anti-influenza agents conjugated with anti-inflammatory activity
EP2855745A4 (en) 2012-06-01 2016-01-20 Momenta Pharmaceuticals Inc METHODS RELATING TO ADALIMUM AB
WO2014031498A1 (en) 2012-08-18 2014-02-27 Academia Sinica Cell-permeable probes for identification and imaging of sialidases
TWI563091B (en) 2012-08-20 2016-12-21 Academia Sinica Large scale enzymatic synthesis of oligosaccharides
WO2014031762A1 (en) 2012-08-21 2014-02-27 Academia Sinica Benzocyclooctyne compounds and uses thereof
AU2013337926B2 (en) 2012-10-30 2017-12-21 Esperance Pharmaceuticals, Inc. Antibody/drug conjugates and methods of use
AU2013339038B2 (en) * 2012-11-05 2017-12-21 Zenyaku Kogyo Kabushikikaisha Antibody and antibody composition production method
WO2014078373A1 (en) 2012-11-13 2014-05-22 Iogenetics, Llc Antimicrobial compositions
CN103045647A (zh) * 2012-11-29 2013-04-17 大连大学 核心岩藻糖基转移酶基因沉默细胞模型的建立及鉴定方法
GB201305986D0 (en) 2013-04-03 2013-05-15 Asociaci N Ct De Investigaci N Cooperativa En Biomateriales Synthesis and use of isotopically-labelled glycans
AU2014253040A1 (en) 2013-04-13 2015-11-05 Universidade De Coimbra Platform for targeted delivery to stem cells and tumor cells and uses thereof
CN104225616A (zh) 2013-06-08 2014-12-24 中南大学 一种靶向卵巢癌干细胞的抗肿瘤生物制剂
EP3013365B1 (en) 2013-06-26 2019-06-05 Academia Sinica Rm2 antigens and use thereof
WO2014210564A1 (en) 2013-06-27 2014-12-31 Academia Sinica Glycan conjugates and use thereof
US10202590B2 (en) 2013-09-05 2019-02-12 Vib Vzw Cells producing Fc-containing molecules having altered glycosylation patterns and methods and use thereof
US9782476B2 (en) 2013-09-06 2017-10-10 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
EP3043647A4 (en) 2013-09-12 2017-05-10 Teva Pharmaceutical Industries Ltd. Gene expression biomarkers of laquinimod responsiveness
CN103436627B (zh) 2013-09-13 2016-02-03 四川大学华西医院 一种恶性乳腺癌干细胞的筛查试剂盒
WO2015054039A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Fc CONTAINING POLYPEPTIDES HAVING INCREASED BINDING TO FcGammaRIIB
CA2937123A1 (en) * 2014-01-16 2015-07-23 Academia Sinica Compositions and methods for treatment and detection of cancers
US10150818B2 (en) 2014-01-16 2018-12-11 Academia Sinica Compositions and methods for treatment and detection of cancers
TWI682033B (zh) * 2014-03-17 2020-01-11 泉盛生物科技股份有限公司 製造具有經修飾的糖苷化作用之重組糖蛋白之方法
WO2015148915A1 (en) 2014-03-27 2015-10-01 Academia Sinica Reactive labelling compounds and uses thereof
KR20170003720A (ko) * 2014-05-27 2017-01-09 아카데미아 시니카 항-ｃｄ20 글리코항체 및 이의 용도
US10118969B2 (en) 2014-05-27 2018-11-06 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
CA2950423A1 (en) 2014-05-27 2015-12-03 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
KR102512592B1 (ko) 2014-05-27 2023-03-21 아카데미아 시니카 항-ｈｅｒ2 글리코항체 및 이의 용도
CN106714829A (zh) 2014-05-28 2017-05-24 中央研究院 抗TNF‑α醣抗体及其用途
CN106661129B (zh) 2014-08-19 2021-02-05 美天施生物科技有限两合公司 对ssea4抗原具有特异性的嵌合抗原受体
JP6401380B2 (ja) 2014-08-22 2018-10-10 アカデミア シニカＡｃａｄｅｍｉａ Ｓｉｎｉｃａ 新規のグリカンコンジュゲート及びその使用
CA2960712A1 (en) 2014-09-08 2016-03-17 Academia Sinica Human inkt cell activation using glycolipids
CN107135654B (zh) 2014-09-12 2021-10-29 加利福尼亚大学董事会 巨胞饮人类抗cd46抗体和靶向癌症疗法
US10495645B2 (en) 2015-01-16 2019-12-03 Academia Sinica Cancer markers and methods of use thereof
US9975965B2 (en) 2015-01-16 2018-05-22 Academia Sinica Compositions and methods for treatment and detection of cancers
WO2016118090A1 (en) 2015-01-23 2016-07-28 Agency For Science, Technology And Research Cancer specific antigen-binding proteins
AU2015378564A1 (en) 2015-01-24 2017-07-13 Academia Sinica Novel glycan conjugates and methods of use thereof
CA2973886A1 (en) * 2015-01-30 2016-08-04 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US20170283878A1 (en) 2015-12-11 2017-10-05 Academia Sinica Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers
WO2017156192A1 (en) 2016-03-08 2017-09-14 Academia Sinica Methods for modular synthesis of n-glycans and arrays thereof
AU2017239637A1 (en) 2016-03-29 2018-11-15 Obi Pharma, Inc. Antibodies, pharmaceutical compositions and methods
EP3500594A4 (en) 2016-08-22 2020-03-11 Cho Pharma Inc. ANTIBODIES, BINDING FRAGMENTS AND METHOD FOR USE
WO2018039373A1 (en) 2016-08-24 2018-03-01 Cho Pharma Inc Endoglycosidase mutants for glycoprotein remodeling and methods of using it
TWI822055B (zh) 2016-11-21 2023-11-11 台灣浩鼎生技股份有限公司 共軛生物分子、醫藥組成物及方法
WO2020006176A1 (en) 2018-06-27 2020-01-02 Obi Pharma, Inc. Glycosynthase variants for glycoprotein engineering and methods of use

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5395541A (en) * 1989-10-27 1995-03-07 The Procter & Gamble Company Cleaning composition containing a type II endoglycosidase
US6984630B1 (en) * 1998-09-21 2006-01-10 Laboratoires Goemar S.A. Endofucanases and method using same for preparing fuco-oligosaccharides from fucanes, bacterium producing endofucanases and uses of fuco-oligosaccharides for plant protection
US7090973B1 (en) 1999-04-09 2006-08-15 Oscient Pharmaceuticals Corporation Nucleic acid sequences relating to Bacteroides fragilis for diagnostics and therapeutics
WO2011005756A1 (en) * 2009-07-06 2011-01-13 Puretech Ventures, Llc Delivery of agents targeted to microbiota niches
WO2013012066A1 (ja) 2011-07-21 2013-01-24 京セラ株式会社 照明装置、イメージセンサヘッドおよびこれを備える読取装置
WO2013120066A1 (en) 2012-02-10 2013-08-15 University Of Maryland, Baltimore Chemoenzymatic glycoengineering of antibodies and fc fragments thereof
WO2015026484A1 (en) * 2013-07-26 2015-02-26 Academia Sinica Antibody-mediated anti-tumor activity induced by reishi mushroom polysaccharides

Non-Patent Citations (17)

* Cited by examiner, † Cited by third party
Title
"Bacteroides fragilis NCTC 9343 putative exported alpha-L-fucosidase protein", DATABASE EMBL, 3 March 2005 (2005-03-03)
"Bacteroides thetaiotaomicron VPI-5482 alpha-L-fucosidase precursor", DATABASE EMBL, 6 January 2006 (2006-01-06)
"Molecular Cloning: A Laboratory Manual", 1989, COLD SPRING HARBOR LABORATORY PRESS
ALTSCHUL ET AL., J. MOL. BIOL., vol. 215, 1990, pages 403 - 10
ALTSCHUL ET AL., NUCLEIC ACIDS RES, vol. 25, no. 17, 1997, pages 3389 - 3402
CURRENT ANALYTICAL CHEMISTRY, vol. 1, no. 1, 2005, pages 28 - 57
FUJITA ET AL., BIOCHIM. BIOPHYS. ACTA, vol. 1528, 2001, pages 9 - 14
HARUKO SAKURAMA ET AL.: "Differences in the substrate specificities and active-site structures of two [alpha]-L-fucosidases (Glycoside Hydrolasae Family 29) from Bacteroides thetaiotaomicron", BIOSCIENCE BIOTECHNOLOGY BIOCHEMISTRY, vol. 76, no. 5, 23 May 2012 (2012-05-23), pages 1022 - 1024
John Wiley & Sons, Inc.; "GenBank", Database accession no. AAA26738.1
KARLINALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 87, 1990, pages 2264 - 68
KARLINALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 5873 - 77
MACFARLANE ET AL.: "Formation of glycoprotein degrading enzymes by Bacteroides fragilis", FEMS MICROBIOLOGY LETTERS, vol. 77, no. Iss.2-3, 1 January 1991 (1991-01-01), pages 289 - 294, XP023971427 *
PUIGBÒ ET AL., NUCLEIC ACIDS RESEARCH, vol. 35, no. S2, 2007, pages W126 - W130
SHIH-FEN LIAO ET AL.: "Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes", PNAS, vol. 110, no. 34, 1 August 2013 (2013-08-01), pages 13809 - 13814, XP055423499, DOI: 10.1073/pnas.1312457110
TYAGARAJAN ET AL., GLYCOBIOLOGY, vol. 6, 1996, pages 83 - 93
VERMEER ET AL., BIOPHYS J, vol. 78, 2000, pages 394 - 404
WEI HUANG ET AL.: "Chemoenzymatic glycoengineering of intact IgG antibodies for gain of functions", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 134, no. 29, 25 July 2012 (2012-07-25), pages 12308 - 12318, XP055531856, DOI: 10.1021/ja3051266

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10317393B2 (en) 2007-03-23 2019-06-11 Academia Sinica Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells
US10274488B2 (en) 2008-07-15 2019-04-30 Academia Sinica Glycan arrays on PTFE-like aluminum coated glass slides and related methods
US11377485B2 (en) 2009-12-02 2022-07-05 Academia Sinica Methods for modifying human antibodies by glycan engineering
US11267870B2 (en) 2009-12-02 2022-03-08 Academia Sinica Methods for modifying human antibodies by glycan engineering
US10087236B2 (en) 2009-12-02 2018-10-02 Academia Sinica Methods for modifying human antibodies by glycan engineering
US10338069B2 (en) 2010-04-12 2019-07-02 Academia Sinica Glycan arrays for high throughput screening of viruses
US10130714B2 (en) 2012-04-14 2018-11-20 Academia Sinica Enhanced anti-influenza agents conjugated with anti-inflammatory activity
US10214765B2 (en) 2012-08-18 2019-02-26 Academia Sinica Cell-permeable probes for identification and imaging of sialidases
US10086054B2 (en) 2013-06-26 2018-10-02 Academia Sinica RM2 antigens and use thereof
US9981030B2 (en) 2013-06-27 2018-05-29 Academia Sinica Glycan conjugates and use thereof
US10111951B2 (en) 2013-09-06 2018-10-30 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US10918714B2 (en) 2013-09-06 2021-02-16 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US10150818B2 (en) 2014-01-16 2018-12-11 Academia Sinica Compositions and methods for treatment and detection of cancers
US9982041B2 (en) 2014-01-16 2018-05-29 Academia Sinica Compositions and methods for treatment and detection of cancers
US10119972B2 (en) 2014-03-27 2018-11-06 Academia Sinica Reactive labelling compounds and uses thereof
US10023892B2 (en) 2014-05-27 2018-07-17 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10118969B2 (en) 2014-05-27 2018-11-06 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10005847B2 (en) 2014-05-27 2018-06-26 Academia Sinica Anti-HER2 glycoantibodies and uses thereof
US11884739B2 (en) 2014-05-27 2024-01-30 Academia Sinica Anti-CD20 glycoantibodies and uses thereof
US11319567B2 (en) 2014-05-27 2022-05-03 Academia Sinica Fucosidase from bacteroides and methods using the same
US10618973B2 (en) 2014-05-27 2020-04-14 Academia Sinica Anti-HER2 glycoantibodies and uses thereof
US11332523B2 (en) 2014-05-28 2022-05-17 Academia Sinica Anti-TNF-alpha glycoantibodies and uses thereof
US9879042B2 (en) 2014-09-08 2018-01-30 Academia Sinica Human iNKT cell activation using glycolipids
US10533034B2 (en) 2014-09-08 2020-01-14 Academia Sinica Human iNKT cell activation using glycolipids
US10495645B2 (en) 2015-01-16 2019-12-03 Academia Sinica Cancer markers and methods of use thereof
US9975965B2 (en) 2015-01-16 2018-05-22 Academia Sinica Compositions and methods for treatment and detection of cancers
US10342858B2 (en) 2015-01-24 2019-07-09 Academia Sinica Glycan conjugates and methods of use thereof
US10336784B2 (en) 2016-03-08 2019-07-02 Academia Sinica Methods for modular synthesis of N-glycans and arrays thereof
US10538592B2 (en) 2016-08-22 2020-01-21 Cho Pharma, Inc. Antibodies, binding fragments, and methods of use
US10260056B2 (en) 2017-03-17 2019-04-16 New England Biolabs, Inc. Cleavage of fucose in N-glycans
WO2021026264A1 (en) * 2019-08-05 2021-02-11 Cho Pharma, Inc. Fusion protein for remodeling antibody glycoform
US11851691B2 (en) 2019-08-05 2023-12-26 CHO Pharma Inc. Fusion protein for remodeling antibody glycoform
WO2022261021A1 (en) * 2021-06-07 2022-12-15 Amgen Inc. Using fucosidase to control afucosylation level of glycosylated proteins

Also Published As

Publication number Publication date
JP6894239B2 (ja) 2021-06-30
JP7093612B2 (ja) 2022-06-30
CN107406495A (zh) 2017-11-28
JP2018509385A (ja) 2018-04-05
US20200165649A1 (en) 2020-05-28
AU2021200644A1 (en) 2021-03-04
AU2021200644B2 (en) 2024-07-18
DK3149045T3 (da) 2023-03-06
IL249183A0 (en) 2017-01-31
TWI654202B (zh) 2019-03-21
US11319567B2 (en) 2022-05-03
JP2020171320A (ja) 2020-10-22
CN107406495B (zh) 2021-07-27
CA2950577A1 (en) 2015-12-03
US20160017390A1 (en) 2016-01-21
WO2015184009A1 (en) 2015-12-03
EP3149161A4 (en) 2017-12-27
CN107074945B (zh) 2021-08-24
FI3149045T3 (fi) 2023-03-20
JP2017517518A (ja) 2017-06-29
IL249195B (en) 2021-10-31
KR20170098954A (ko) 2017-08-30
AU2015267052A1 (en) 2016-12-15
IL249183B (en) 2020-11-30
US20150344544A1 (en) 2015-12-03
CN106661562A (zh) 2017-05-10
JP2017520241A (ja) 2017-07-27
EP3149045A1 (en) 2017-04-05
IL249195A0 (en) 2017-01-31
EP3149045A4 (en) 2017-12-27
DK3245225T3 (da) 2021-10-18
KR20170005142A (ko) 2017-01-11
JP2020041003A (ja) 2020-03-19
EP3149045B1 (en) 2023-01-18
CN107074945A (zh) 2017-08-18
KR20230033737A (ko) 2023-03-08
EP3149161A1 (en) 2017-04-05
EP3245225A4 (en) 2018-10-31
US10023892B2 (en) 2018-07-17
EP3245225A1 (en) 2017-11-22
EP3904388A1 (en) 2021-11-03
TWI717319B (zh) 2021-02-01
TW201613970A (en) 2016-04-16
EP3149161B1 (en) 2021-07-28
AU2015267051A1 (en) 2017-01-12
AU2015267051B2 (en) 2022-03-17
KR20170010003A (ko) 2017-01-25
KR102821413B1 (ko) 2025-06-17
KR102576850B1 (ko) 2023-09-11
US20190119713A1 (en) 2019-04-25
KR20230004916A (ko) 2023-01-06
CA2950423A1 (en) 2015-12-03
EP3245225B1 (en) 2021-09-22
TW201614068A (en) 2016-04-16

Similar Documents

Publication Publication Date Title
US11319567B2 (en) Fucosidase from bacteroides and methods using the same
AU2012307461B2 (en) Endoglycosidase from Streptococcus pyogenes and methods using it
Giddens et al. Endo-F3 glycosynthase mutants enable chemoenzymatic synthesis of core-fucosylated triantennary complex type glycopeptides and glycoproteins
Davidson et al. Asparagine-linked oligosaccharide processing in lepidopteran insect cells. Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector infected Spodoptera frugiperda (IPLB-SF-21AE) cells
US8323908B2 (en) Method of assessing glycosylation state or functional quality of an IgG containing sample
EP2930241B1 (en) Novel recombinant factor c and method for producing same, and method for measuring endotoxin
JP7557896B2 (ja) Ｏ－糖タンパク質のためのプロテアーゼ及び結合ポリペプチド
Takashima et al. Novel endo-β-N-acetylglucosaminidases from Tannerella species hydrolyze multibranched complex-type N-glycans with different specificities
Ashida et al. 1, 6-α-L-Fucosidases from Bifidobacterium longum subsp. infantis ATCC 15697 involved in the degradation of core-fucosylated N-glycan
CA3249096A1 (en) Fucosidase mutants and the use thereof
Lyu et al. Identification and characterization of emNagII, a novel β-1, 2-N-acetylglucosaminidase from Elizabethkingia meningoseptica
EP2281036A2 (en) Endoglyosidases that cleave o-linked glycans
Thoma et al. Identification, characterization and expression of β-galactosidases from Arion species (Mollusca). Biomolecules 2022, 12, 1578
Takegawa et al. Endoglycosidases (Glycoproteins)
JP2017055675A (ja) 改変複合型糖鎖加水分解酵素
Zu et al. Application of a Novel Α-Galactosidase from Bacteroides Fragilis on Structural Analysis of Raffinose Family Oligosaccharides

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: 15800191

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 249183

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2016569720

Country of ref document: JP

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2950577

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 20167036507

Country of ref document: KR

Kind code of ref document: A

REEP Request for entry into the european phase

Ref document number: 2015800191

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2015800191

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2015267051

Country of ref document: AU

Date of ref document: 20150527

Kind code of ref document: A