By–Passing Immunization: Building High Affinity Human Antibodies by Chain Shuffling View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1992-07-01

AUTHORS

James D. Marks, Andrew D. Griffiths, Magnus Malmqvist, Tim P. Clackson, Jacqueline M. Bye, Greg Winter

ABSTRACT

Diverse antibody libraries can be displayed on the surface of filamentous bacteriophage, and selected by panning of the phage with antigen. This allows human antibodies to be made directly in vitro without prior immunization, thus mimicking the primary immune response1. Here we have improved the affinity of one such “primary” antibody by sequentially replacing the heavy and light chain variable (V) region genes with repertoires of V–genes (chain shuffling)2 obtained from unimmunized donors. For a human phage antibody for the hapten 2–phenyloxazol–5–one (phOx) (Kd=3.2×10−7 M), we shuffled the light chains and isolated an antibody with a 20 fold improved affinity. By shuffling the first two hypervariable loops of the heavy chain, we isolated an antibody with a further 15–fold improved affinity. The reshuffled antibody differed in five of the six hypervariable loops from the original antibody and the affinity for phOx (Kd=1.1×10−9 M) was comparable to that of mouse hybridomas from the tertiary immune response. Reshuffling offers an alternative to random point mutation for affinity maturation of human antibodies in vitro. More... »

PAGES

779-783

Journal

TITLE

Bio/Technology

ISSUE

7

VOLUME

10

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  • Methods Of Treating And Monitoring Disease With Antibodies
  • Antibodies Against The Rgm A Protein And Uses Thereof
  • Polynucleotides Encoding An Anti-Beta-Amyloid Monoclonal Antibody
  • Notch1 Receptor Antibodies And Methods Of Treatment
  • Polynucleotides Encoding Notch Receptor Antibodies
  • Therapeutic Targets In Cancer
  • Methods And Compositions For Modulating Hepsin Activation Of Macrophage-Stimulating Protein
  • Anti-Gp73 Monoclonal Antibodies And Methods Of Obtaining The Same
  • Anti-5t4 Antibodies And Uses Thereof
  • Methods Of Determining Cellular Chemosensitivity
  • Methods And Compositions For Assessing Responsiveness Of B-Cell Lymphoma To Treatment With Anti-Cd40 Antibodies
  • Antibody Against The Csf-1r
  • Vaccine Compositions And Methods For Restoring Nkg2d Pathway Function Against Cancers
  • Combination Therapies Employing Gitr Binding Molecules
  • Anti-Ox40 Antibodies And Methods Of Use
  • Antibodies To A Non-Ligand Binding Region Of At Least Two Notch Receptors
  • Anti-Cxcr4 Antibodies And Antibody-Drug Conjugates
  • System And Method For Oct Depth Calibration
  • Il-17 Binding Proteins
  • Anti-Alphavbeta1 Integrin Compounds And Methods
  • Chemically Encoded Spatially Addressed Library Screening Platforms
  • Methods Of Culturing And Expanding Mesenchymal Stem Cells
  • Kits Containing Dll3 Antibody Drug Conjugates
  • Monovalent Binding Proteins
  • Human Inkt Cell Activation Using Glycolipids
  • Trispecific Antibodies
  • Anti-Cd83 Antibodies And Use Thereof
  • Nanoparticles Containing Polymeric Nucleic Acid Homologs
  • Antibodies Specific For Tgf-Beta And Methods For Treating Thereof
  • Internalizing Human Monoclonal Antibodies Targeting Prostate And Other Cancer Cells
  • Cell Culture Methods To Reduce Acidic Species
  • Humanized Anti-Beta7 Antagonists And Uses Therefor
  • Methods For Treating Progressive Multiple Sclerosis
  • Il-17 Binding Proteins
  • Anti-Ox40 Antibodies And Methods Of Use
  • Methods To Control Protein Heterogeneity
  • Hcv Antigen-Antibody Combination Assay And Methods And Compositions For Use Therein
  • Composition And Method For The Diagnosis And Treatment Of Iron-Related Disorders
  • Method Of Treatment With Antibodies Having Specificity For Human Ox40
  • Binding Members
  • Hemagglutinin Polypeptides, And Reagents And Methods Relating Thereto
  • Smooth Transition Catheters
  • Cancer Treatment Kits Comprising Therapeutic Antibody Conjugates That Bind To Aminophospholipids
  • Nucleotide And Amino Acid Sequences Encoding An Exported Protein 1 Derived From Plasmodium Vivax And Uses Thereof
  • Nucleotide And Amino Acid Sequences Encoding An Exported Protein 1 Derived From Plasmodium Vivax And Uses Thereof
  • Peptides And Methods Using Same For Diagnosis And Treatment Of Amyloid-Associated Disease
  • Ip-10 Antibodies And Their Uses
  • Antibodies Associated With Alterations In Bone Density
  • Dipeptide Analogs For Treating Conditions Associated With Amyloid Fibril Formation
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Recombinant Il-9 Antibodies And Uses Thereof
  • High Throughput Generation And Affinity Maturation Of Humanized Antibody
  • Antibodies Against Glucocorticoid-Induced Tumor Necrosis Factor Receptor (Gitr) And Uses Thereof
  • Methods For Inducing Or Enhancing An Immune Response By Administering Agonistic Gitr-Binding Antibodies
  • Methods For Identifying Safe And Functional Humanized Antibodies
  • Polynucleotides Encoding Antibodies Directed Against Amyloid-Beta Peptide
  • Host Cell Specific Binding Molecules Capable Of Neutralizing Viruses And Uses Thereof
  • Monoclonal Antibody
  • Human Endothelin Receptor Antibody And Use Thereof
  • Human Endothelin Receptor Antibody And Use Thereof
  • Nucleic Acid Molecule Encoding A Specific Il-1r1 Antibody
  • Assay For Cardiac Troponin Autoantibodies
  • Cancer Treatment Kits Comprising Therapeutic Antibody Conjugates That Bind To Aminophospholipids
  • Anti-Cxcr4 Antibodies And Antibody-Drug Conjugates
  • Binding Members
  • Specific Binding Proteins And Uses Thereof
  • Neovascular-Targeted Immunoconjugates
  • Anti-Nkp46 Antibodies, Toxin Conjugates, And Therapeutic Use Of Same
  • High Potency Recombinant Antibodies And Method For Producing Them
  • Antibody Peg Positional Isomers, Compositions Comprising Same, And Use Thereof
  • Method For Making Multispecific Antibodies Having Heteromultimeric And Common Components
  • Methods For Treating Juvenile Idiopathic Arthritis
  • Treatment Of Fibrosis With Interleukin-11 Receptor Alpha Antibody
  • Recombinant Il-9 Antibodies And Uses Thereof
  • High Throughput Generation And Affinity Maturation Of Humanized Antibody
  • Anti-Ige Antibodies And Method Of Improving Polypeptides
  • Human-Murine Chimeric Antibodies Against Respiratory Syncytial Virus
  • Antibodies Against Glucocorticoid-Induced Tumor Necrosis Factor Receptor (Gitr) And Uses Thereof
  • Methods For Inducing Or Enhancing An Immune Response By Administering Agonistic Gitr-Binding Antibodies
  • Host Cell Specific Binding Molecules Capable Of Neutralizing Viruses And Uses Thereof
  • Monoclonal Antibody
  • Therapeutic Targets In Cancer
  • Antibodies To A Non-Ligand Binding Region Of At Least Two Notch Receptors
  • Anti-Cxcr4 Antibodies And Antibody-Drug Conjugates
  • Compositions And Methods For Diagnosing And Treating Cancer
  • Notch1 Receptor Antibodies And Methods Of Treatment
  • Polynucleotides Encoding Notch Receptor Antibodies
  • Multispecific Fab Fusion Proteins And Use Thereof
  • Modified Immunoglobulin Molecules That Specifically Bind Human Vegf And Dll4
  • Therapeutic Peptides
  • Rationally Designed, Synthetic Antibody Libraries And Uses Therefor
  • Ip-10 Antibodies And Their Uses
  • Anti-Cd79b Antibodies And Immunoconjugates And Methods Of Use
  • Antibodies Against Glucocorticoid-Induced Tumor Necrosis Factor Receptor (Gitr) And Uses Thereof
  • Stable And Soluble Antibodies Inhibiting Tnf Alpha
  • Neovascular-Targeted Immunoconjugates
  • Antibodies Specific To Human Poliovirus Receptor (Pvr)
  • Immunoglobulin Variable Region Cassette Exchange
  • Humanized Antibodies To Interferon Alpha Receptor-1 (Ifnar-1)
  • Use Of Human Tnfα Antibodies For Treatment Of Erosive Polyarthritis
  • Methods Of Improving Vaccine Immunogenicity
  • Methods Of Inducing Or Enhancing An Immune Response In A Subject Having Cancer By Administering Gitr Antibodies
  • Heterodimeric Proteins
  • Therapeutic Dll4 Binding Proteins
  • Immuno-Pet Imaging Of Antibodies And Immunoconjugates And Uses Therefor
  • Method Employing Bispecific Antibodies
  • Albumin Binding Antibodies And Binding Fragments Thereof
  • Human Antibodies That Bind Human Tnfα
  • Carbohydrate Antibodies, Pharmaceutical Compositions And Uses Thereof
  • Assay For Measurement Of Antibodies Binding To A Therapeutic Monoclonal Antibody
  • Humanized Antibodies To Interferon Alpha Receptor-1 (Ifnar-1)
  • Anti-Cd26 Antibodies And Methods Of Use Thereof
  • Antibody Diversity Generation
  • Ca6 Antigen-Specific Cytotoxic Conjugate And Methods Of Using The Same
  • Method For Treating Pruritus Comprising Administering An Nr10 Antagonist
  • High Throughput Generation And Affinity Maturation Of Humanized Antibody
  • Monoclonal Antibodies Against Hmgb1
  • Anti-Htra1 Antibodies And Methods Of Use Thereof
  • Humanized Anti-Cxcr5 Antibodies, Derivatives Thereof And Their Use
  • Genetically Modified Human Natural Killer Cell Lines
  • Use Of Tnfα Inhibitor For Treatment Of Psoriasis
  • Methods For Treating Visceral Pain Associated With Interstitial Cystitis By Administering Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
  • Methods For Identifying Safe And Functional Humanized Antibodies
  • Use Of Dr6 And P75 Antagonists To Promote Survival Of Cells Of The Nervous System
  • Methods Of Treating And Monitoring Disease With Antibodies
  • Antibodies Against The Rgm A Protein And Uses Thereof
  • Polynucleotides Encoding An Anti-Beta-Amyloid Monoclonal Antibody
  • Polynucleotides Encoding Antibodies Directed Against Amyloid-Beta Peptide
  • Method For Treating Joint Damage
  • Anti-Ngf Antibodies And Methods Using Same
  • Stabilized Liquid Anti-Rsv Antibody Formulations
  • Antigen-Binding Molecule Capable Of Binding To Two Or More Antigen Molecules Repeatedly
  • Method For Making Multispecific Antibodies Having Heteromultimeric And Common Components
  • Ip-10 Antibodies And Their Uses
  • Gitr Antigen Binding Proteins And Methods Of Use Thereof
  • Antibodies Specific For Sclerostin And Methods For Increasing Bone Mineralization
  • Antibody Molecules Specific To Human Tumour Necrosis Factor Alpha
  • Immunoassay Of Analytes In Samples Containing Endogenous Anti-Analyte Antibodies
  • Antibodies Associated With Alterations In Bone Density
  • Combination Therapy For Neoplasia Treatment
  • Stabilized Liquid Anti-Rsv Antibody Formulations
  • Human Endothelin Receptor Antibody And Use Thereof
  • Dipeptide Analogs For Treating Conditions Associated With Amyloid Fibril Formation
  • Peptides And Methods Using Same For Diagnosis And Treatment Of Amyloid-Associated Disease
  • Peptides Directed For Diagnosis And Treatment Of Amyloid-Associated Diseases
  • Human Endothelin Receptor Antibody And Use Thereof
  • Nucleic Acid Molecule Encoding A Specific Il-1r1 Antibody
  • Assay For Cardiac Troponin Autoantibodies
  • System And Method For Catheter Steering And Operation
  • Nucleotide And Amino Acid Sequences Encoding An Exported Protein 1 Derived From Plasmodium Vivax And Uses Thereof
  • Nucleotide And Amino Acid Sequences Encoding An Exported Protein 1 Derived From Plasmodium Vivax And Uses Thereof
  • Use Of Hmgb Fragments As Anti-Inflammatory Agents
  • System And Method For Oct Depth Calibration
  • Decreasing Lactate Level And Increasing Polypeptide Production By Downregulating The Expression Of Lactate Dehydrogenase And Pyruvate Dehydrogenase Kinase
  • Proteome Epitope Tags And Methods Of Use Thereof In Protein Modification Analysis
  • Il-1 Binding Proteins
  • Proteome Epitope Tags And Methods Of Use Thereof In Protein Modification Analysis
  • Methods For Identifying And Isolating Cells Expressing A Polypeptide
  • Hmg1 Antibody For Treating Inflammatory Conditions
  • Humanized Anti-Beta7 Antagonists And Uses Therefor
  • Methods For Treating Progressive Multiple Sclerosis
  • Monovalent Binding Proteins
  • Systems For Indicating Parameters In An Imaging Data Set And Methods Of Use
  • Method To Improve Virus Filtration Capacity
  • Unnatural Reactive Amino Acid Genetic Code Additions
  • Bispecific Heterodimeric Fusion Proteins Containing Il-15-Il-15rα Fc-Fusion Proteins And Pd-1 Antibody Fragments
  • Method For Making Heteromultimeric Molecules
  • Antibody To Gdf8 And Uses Thereof
  • Il-1 Binding Proteins
  • Methods Of Controlling Proliferation And Differentiation Of Stem And Progenitor Cells
  • Novel Anti-Plasmodium Parasite Antibodies
  • Method For In Vitro Molecular Evolution Of Protein Function
  • Composition And Method For Diversification Of Target Sequences
  • Recombination Of Polynucleotide Sequences Using Random Or Defined Primers
  • Methods And Compositions For Cellular And Metabolic Engineering
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Methods And Compositions For Cellular And Metabolic Engineering
  • Method For Detecting Highly Functional Polypeptides Or Nucleic Acids
  • Methods For Controlling The Galactosylation Profile Of Recombinantly-Expressed Proteins
  • Cell Culture Compositions With Antioxidants And Methods For Polypeptide Production
  • Fusion Proteins For Treating Cancer And Related Methods
  • Inhibitors Of Memapsin 2 And Use Thereof
  • Methods To Modulate Lysine Variant Distribution
  • Peptide Nanostructure-Coated Electrodes
  • Proteome Epitope Tags And Methods Of Use Thereof In Protein Modification Analysis
  • Nucleic Acids Encoding Antibodies To Matrix Metalloproteinase 9
  • Decreasing Lactate Level And Increasing Polypeptide Production By Downregulating The Expression Of Lactate Dehydrogenase And Pyruvate Dehydrogenase Kinase
  • Proteome Epitope Tags And Methods Of Use Thereof In Protein Modification Analysis
  • Antibody Formulations
  • Methods For Identifying And Isolating Cells Expressing A Polypeptide
  • Il-1 Binding Proteins
  • Low Acidic Species Compositions And Methods For Producing And Using The Same
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Methods For Producing Recombined Antibodies
  • Antibodies Specific For Tgf-Β And Methods Of Treatment Thereof
  • Inhibition And Treatment Of Prostate Cancer Metastasis
  • Biomarker Of Asbestos Exposure And Mesothelioma
  • Anti-Dll3 Antibodies
  • Combination Therapies For Treatment Of Cancer
  • High Concentration Antibody Formulations
  • Ph Adjustment To Improve Thaw Recovery Of Cell Banks
  • Antibody Molecules Having Specificity For Human Il-1Β
  • Il-17 Binding Proteins
  • Methods And Compositions For Polypeptide Engineering
  • Methods For Modular Synthesis Of N-Glycans And Arrays Thereof
  • Protein Recovery
  • Alvocidib Prodrugs Having Increased Bioavailability
  • Synthesis Of Hybrid Polynucleotide Molecules Using Single-Stranded Polynucleotide Molecules
  • Rnai Vitamin D Conjugates
  • Methods For Identifying And Isolating Cells Expressing A Polypeptide
  • Uses Of Wnt Polypeptides
  • Decreasing Lactate Level And Increasing Polypeptide Production By Down Regulating The Expression Of Lactate Dehydrogenase And Pyruvate Dehydrogenase Kinase
  • Yeast Cell Surface Display Of Proteins And Uses Thereof
  • Ctla4-Binding Protein Peptide-Linker Masks
  • Low Acidic Species Compositions And Methods For Producing And Using The Same
  • Compositions And Methods For Detecting And Quantifying Host Cells Protein In Cell Lines And Recombinant Polypeptide Products
  • Profiling Peptides And Methods For Sensitivity Profiling
  • Proteome Epitope Tags And Methods Of Use Thereof In Protein Modification Analysis
  • Cell-Permeable Probes For Identification And Imaging Of Sialidases
  • Methods Of Expanding Stem And Progenitor Cells And Expanded Cell Populations Obtained Thereby
  • Heterodimeric Antibodies That Bind Cd3 And Tumor Antigens
  • Systems And Methods For Amplifying Light
  • Multiplex Protein Fractionation
  • Ionic Strength-Mediated Ph Gradient Ion Exchange Chromatography
  • Purification Of Proteins Using Hydrophobic Interaction Chromatography
  • Protein Purification Using Displacement Chromatography
  • Methods For Controlling The Galactosylation Profile Of Recombinantly-Expressed Proteins
  • Protein Purification Methods To Reduce Acidic Species
  • Dual Variable Domain Immunoglobulins And Uses Thereof
  • Methods Of Making Dll3 Antibody Drug Conjugates
  • Nucleic Acid Encoding Dll3 Antibodies
  • Anti-Gp73 Monoclonal Antibodies And Methods Of Obtaining The Same
  • Methods And Compositions Comprising Purified Recombinant Polypeptides
  • Proteome Epitope Tags And Methods Of Use Thereof In Protein Modification Analysis
  • Alkynyl Sugar Analogs For Labeling And Visualization Of Glycoconjugates In Cells
  • Protein Purification Methods To Reduce Acidic Species
  • Antibodies To Matrix Metalloproteinase 9
  • Protein Isoform Discrimination And Quantitative Measurements Thereof
  • Thermomyces Lanuginosus Kinesin Motor Protein And Methods Of Screening For Modulators Of Kinesin Proteins
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Decreasing Lactate Level And Increasing Polypeptide Production By Downregulating The Expression Of Lactate Dehydrogenase And Pyruvate Dehydrogenase Kinase
  • Methods For Identifying And Isolating Cells Expressing A Polypeptide
  • Low Acidic Species Compositions And Methods For Producing And Using The Same
  • Clotting Factor-Fc Chimeric Proteins To Treat Hemophilia
  • Borrelia Antigens
  • Antibody To Gdf8 And Uses Thereof
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • System For Antibody Expression And Assembly
  • Communications Network System And Methods For Using Same
  • Direct Screening Method
  • Peptides And Methods Using Same For Diagnosis And Treatment Of Amyloid-Associated Disease
  • Guidewire With Centering Mechanism
  • High Affinity Antibodies Against Hmgb1 And Methods Of Use Thereof
  • Exonuclease-Mediated Nucleic Acid Reassembly In Directed Evolution
  • Method Of Treating Tumors
  • Culturing Of Mesenchymal Stem Cells With Fgf4 And Nicotinamide
  • Compositions And Methods For Diagnosing And/Or Treating Influenza Infection
  • Method For Inhibiting Bone Resorption
  • Methods For Treating Juvenile Idiopathic Arthritis
  • Inhibition And Treatment Of Prostate Cancer Metastasis
  • Optical-Electrical Rotary Joint And Methods Of Use
  • Low Acidic Species Compositions And Methods For Producing And Using The Same
  • Ctla4-Binding Protein Peptide-Linker Masks
  • Thermomyces Lanuginosus Kinesin Motor Protein And Methods Of Screening For Modulators Of Kinesin Proteins
  • Methods For Identifying And Isolating Cells Expressing A Polypeptide
  • Methods For Identifying And Isolating Cells Expressing A Polypeptide
  • Low Acidic Species Compositions And Methods For Producing And Using The Same
  • Clotting Factor-Fc Chimeric Proteins To Treat Hemophilia
  • Borrelia Antigens
  • Antibody To Gdf8 And Uses Thereof
  • System For Antibody Expression And Assembly
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Protein Purification Methods To Reduce Acidic Species
  • Multispecific Antibodies
  • Monoclonal Antibody That Binds Human Notch2 And Notch3
  • Decreasing Lactate Level And Increasing Polypeptide Production By Downregulating The Expression Of Lactate Dehydrogenase And Pyruvate Dehydrogenase Kinase
  • High Affinity Antibodies Against Hmgb1 And Methods Of Use Thereof
  • Antibodies To Matrix Metalloproteinase 9
  • Therapeutic Dll4 Binding Proteins
  • Antibody/T-Cell Receptor Chimeric Constructs And Uses Thereof
  • Stable Igg4 Based Binding Agent Formulations
  • Internalizing Human Monoclonal Antibodies Targeting Prostate Cancer Cells In Situ
  • Method Of Modifying Isoelectric Point Of Antibody Via Amino Acid Substitution In Cdr
  • Specific Binding Members, Materials And Methods
  • Ca6 Antigen-Specific Cytotoxic Conjugate And Methods Of Using The Same
  • Antibodies To Lymphotoxin-Α
  • Neovascular-Targeted Immunoconjugates
  • Ip-10 Antibodies And Their Uses
  • Gitr Antibodies And Methods Of Inducing Or Enhancing An Immune Response
  • Anti-Nr10 Antibody And Use Thereof
  • Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
  • Internalizing Human Monoclonal Antibodies Targeting Prostate Cancer Cells In Situ
  • Methods Of Inhibiting Growth Of A Colon Cancer Tumor In A Subject By Administering Monoclonal Antibodies To G Protein-Coupled Receptor 49 (Gpr49)
  • High Affinity Antibodies Against Hmgb1 And Methods Of Use Thereof
  • Alkynyl Sugar Analogs For Labeling And Visualization Of Glycoconjugates In Cells
  • Methods For Controlling The Galactosylation Profile Of Recombinantly-Expressed Proteins
  • Protein Isoform Discrimination And Quantitative Measurements Thereof
  • Protein Purification Methods To Reduce Acidic Species
  • Antibodies To Matrix Metalloproteinase 9
  • Alvocidib Prodrugs Having Increased Bioavailability
  • Synthesis Of Hybrid Polynucleotide Molecules Using Single-Stranded Polynucleotide Molecules
  • Cell-Permeable Probes For Identification And Imaging Of Sialidases
  • Methods Of Expanding Stem And Progenitor Cells And Expanded Cell Populations Obtained Thereby
  • Polynucleotides Encoding Notch1 Receptor Antibodies
  • Use Of Metal Ions For Modulation Of Protein Glycosylation Profiles Of Recombinant Proteins
  • Identification And Expression Of A Novel Kinesin Motor Protein
  • Methods And Compounds For Detection Of Molecular Targets
  • Alkynyl Sugar Analogs For Labeling And Visualization Of Glycoconjugates In Cells
  • Methods Of Bh3 Profiling
  • Biological Products
  • Enhanced Anti-Influenza Agents Conjugated With Anti-Inflammatory Activity
  • Epitopes
  • Influenza Treatment And/Or Characterization, Human-Adapted Ha Polypeptides; Vaccines
  • Anti-Dll4 Antibodies And Methods Using Same
  • Idiotypic Antibodies And Uses Thereof
  • In Vivo Incorporation Of Unnatural Amino Acids
  • Methods And Compositions For Modulating T Helper (Th) Cell Development And Function
  • Anti-Dll3 Antibody Drug Conjugates
  • Methods And Compositions For Polypeptide Engineering
  • Targeting Regulatory T Cells With Heterodimeric Proteins
  • Rsv-Specific Binding Molecules And Means For Producing Them
  • Optical Coherence Tomography System That Is Reconfigurable Between Different Imaging Modes
  • Multispecific Antibodies
  • Methods And Compositions Comprising Purified Recombinant Polypeptides
  • Anti-Complement Factor H Antibodies
  • Methods Of Evolving A Polynucleotides By Mutagenesis And Recombination
  • Antibody Molecules Having Specificity For Human Ox40
  • Antibody/T-Cell Receptor Chimeric Constructs And Uses Thereof
  • Bispecific Anti-Vegf/Anti-Ang-2 Antibodies And Their Use In The Treatment Of Ocular Vascular Diseases
  • Biological Products
  • Antibodies To Tgf-Β
  • Genetically Modified Human Natural Killer Cell Lines
  • Wnt-7b-Like Polypeptides And Nucleic Acids Encoding Same
  • Targeting Regulatory T Cells With Heterodimeric Proteins
  • Humanized Anti-Cxcr5 Antibodies, Derivatives Thereof And Their Uses
  • Modulation Of T Cell Differentiation For The Treatment Of T Helper Cell Mediated Diseases
  • Production Of Chimeric Antibodies - A Combinatorial Approach
  • Combination Therapy With Co-Stimulatory Factors
  • Antigen-Binding Molecule Capable Of Binding Two Or More Antigen Molecules Repeatedly
  • Production Of Anti-Self Antibodies From Antibody Segment Repertoires And Displayed On Phage
  • Genetically Modified Human Natural Killer Cell Lines
  • Anti-Ige Antibodies
  • Zanamivir Phosphonate Congeners With Anti-Influenza Activity And Determining Oseltamivir Susceptibility Of Influenza Viruses
  • Human Inkt Cell Activation Using Glycolipids With Altered Glycosyl Groups
  • Carbonic Anhydrase Ix (G250) Antibodies And Methods Of Use Thereof
  • Compositions And Methods Relating To Universal Glycoforms For Enhanced Antibody Efficacy
  • Anti Notch-1 Antibodies
  • Stable And Soluble Antibodies Inhibiting Tnfα
  • Optimized Antibody Variable Regions
  • Methods For Affinity Maturation-Based Antibody Optimization
  • Internalizing Erbb2 Antibodies
  • End Selection In Directed Evolution
  • Anti-Igf Antibodies
  • Cancer Treatment Kits Using Antibodies To Aminophospholipids
  • Self-Assembled Fmoc-Ff Hydrogels
  • System And Method For Multipath Processing Of Image Signals
  • Compositions And Methods For Diagnosing And/Or Treating Influenza Infection
  • Method For Inhibiting Bone Resorption
  • Antibodies To Carcinoembryonic Antigen (Cea), Methods Of Making Same, And Uses Thereof
  • Bispecific Anti-Vegf/Anti-Ang-2 Antibodies And Their Use In The Treatment Of Ocular Vascular Diseases
  • Biological Products
  • Chimeric T Cell Receptor Comprising Carbonic Anhydrase Ix (G250) Antibody
  • Antibodies To Lymphotoxin-Α
  • Humanized Antibodies To Interferon Alpha Receptor-1 (Ifnar-1)
  • Humanized Anti-Cd79b Antibodies And Immunoconjugates And Methods Of Use
  • Production Of Anti-Self Antibodies From Antibody Segment Repertoires And Displayed On Phage
  • Anti-Cd79b Antibodies And Immunoconjugates And Methods Of Use
  • Genetically Modified Human Natural Killer Cell Lines
  • Method For Obtaining Antibodies
  • Anti-Her2 Glycoantibodies And Uses Thereof
  • Anti-Notch1 Antibodies
  • Multispecific Anti-Her Antibodies
  • Antibodies To Tgf-Β
  • Ca6 Antigen-Specific Cytotoxic Conjugate And Methods Of Using The Same
  • Nucleic Acids Encoding Anti-Nr10 Antibodies
  • Antibodies That Bind To Cytokine Receptor Nr10
  • Methods And Compositions For Polypeptide Engineering
  • In Vivo Incorporation Of Unnatural Amino Acids
  • Therapeutic Composition For Treatment Of Glioblastoma
  • Modulation Of T Cells With Bispecific Antibodies And Fc Fusions
  • Heterodimeric Antibodies That Bind Somatostatin Receptor 2
  • Antibodies With Modified Isoelectric Points
  • Compositions And Methods For The Treatment Of Tumor Of Hematopoietic Origin
  • Anti-Dll3 Antibody Drug Conjugates
  • Multispecific Antibodies
  • Anti-Complement Factor H Antibodies
  • Methods Of Evolving A Polynucleotides By Mutagenesis And Recombination
  • Multivalent Dll3 Antibodies
  • Anti-Dll3 Antibody Drug Conjugates And Methods Of Use
  • Isolated Monoclonal Anti-Repulsive Guidance Molecule A Antibodies And Uses Thereof
  • Bispecific Antibodies That Bind To Cd38 And Cd3
  • Antibody Molecules Having Specificity For Human Ox40
  • Methods For Isolating Antibodies That Bind Sclerostin
  • Anti-Fgfr3 Antibodies And Methods Using Same
  • Predicting Response To Alvocidib By Mitochondrial Profiling
  • Heterodimeric Antibodies To Cd3 X Cd20
  • Antibody Libraries
  • Methods And Compositions For Polypeptide Engineering
  • Non-Affinity Purification Of Proteins
  • Anti-Fgfr3 Antibodies And Methods Using Same
  • Chemically Encoded Spatially Addressed Library Screening Platforms
  • Methods And Compositions For Polypeptide Engineering
  • Modulators Of Hepatocyte Growth Factor Activator
  • Method And Apparatus To Identify Vulnerable Plaques With Thermal Wave Imaging Of Heated Nanoparticles
  • Lrp-8 Binding Dual Variable Domain Immunoglobulin Proteins
  • Methods To Control Protein Heterogeneity
  • Composition And Method For The Diagnosis And Treatment Of Iron-Related Disorders
  • Anti-Dll3 Antibody Drug Conjugates And Methods Of Use
  • Benzocyclooctyne Compounds And Uses Thereof
  • Fusion Proteins For Treating Cancer And Related Methods
  • Bispecific Anti-Vegf/Anti-Ang-2 Antibodies And Their Use In The Treatment Of Ocular Vascular Diseases
  • Methods And Compositions Of Matter Concerning April/G70, Bcma, Blys/Agp-3 And Taci
  • Monoclonal Antibodies Against Hmgb1
  • Human Monoclonal Anti-Pd-L1 Antibodies And Methods Of Use
  • Inhibitors Of The Interaction Between Hmgb Polypeptides And Toll-Like Receptor 2 As Anti-Inflammatory Agents
  • Methods And Compositions For Increasing Antibody Production
  • Anti-Sortilin Antibodies And Methods Of Use Thereof
  • Methods For Diagnosing And Treating Inflammatory Bowel Disease
  • Methods Of Treating Diabetes And Compositions Capable Of Same
  • Use Of Anti-Cd83 Agonist Antibodies For Treating Autoimmune Diseases
  • Production Of Humanised Antibodies To Tnfα
  • Methods For Treating Headache Using Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
  • Rationally Designed, Synthetic Antibody Libraries And Uses Therefor
  • Antibodies Against Glucocorticoid-Induced Tumor Necrosis Factor Receptor (Gitr) And Uses Thereof
  • Anti-Trem2 Antibodies And Methods Of Use Thereof
  • Rsv Specific Binding Molecule
  • Production Of Anti-Self Antibodies From Antibody Segment Repertories And Displayed On Phage
  • Antibodies That Bind Il-4 And/Or Il-13 And Their Uses
  • Isolated Polypeptides Of Cd44 And Uses Thereof
  • Dkk1 Antibodies And Methods Of Use
  • Antibody Molecules Which Bind Cd22
  • Genetically Modified Human Natural Killer Cell Lines
  • Dna Encoding Antibody Molecules Which Bind Il-17a And Il-17f
  • Monoclonal Anti-Il-1racp Antibodies
  • Glycoengineered Binding Protein Compositions
  • Anti-Fzd10 Monoclonal Antibodies And Methods For Their Use
  • Anti-Ige Antibodies
  • Rsv-Specific Binding Molecule
  • Anti-Mesothelin Binding Proteins
  • Methods For Diagnosing And Treating Inflammatory Bowel Disease
  • Mutated Anti-Tnfα Antibodies And Methods Of Their Use
  • Treatment Of Allergic Diseases With Recombinant Antibodies
  • Humanized Antibodies Against Ceacam1
  • Human Antibodies That Bind Human Tnfα
  • Detection Methods Employing Hcv Core Lipid And Dna Binding Domain Monoclonal Antibodies
  • Dual Variable Domain Immunoglobulin And Uses Thereof
  • Cell Culture Media And Methods Of Antibody Production
  • Anti-Cd33 Antibodies And Methods Of Use Thereof
  • Monoclonal Antibody 175 Targeting The Egf Receptor And Derivatives And Uses Thereof
  • Compositions And Methods In Cancer Associated With Altered Expression Of Prlr
  • Therapeutic Targets In Cancer
  • Methods For Treating Bone Cancer By Administering A Nerve Growth Factor Antagonist Antibody
  • Antibodies That Bind The Glutamate Ligand Binding Region Of Notch3
  • Compositions And Methods In Cancer Associated With Altered Expression Of Kcnj9
  • Therapeutic Dll4 Binding Proteins
  • Compositions And Methods For Treatment And Detection Of Cancers
  • Humanized Antibodies That Bind Lgr5
  • Therapeutic Dll4 Binding Proteins
  • Anti-Pdgf-C Antibodies
  • Anti-Il-12/Il-23 Antibodies
  • Anti-Fzd10 Monoclonal Antibodies And Methods For Their Use
  • Dkk1 Antibodies And Methods Of Use
  • Antibody Molecules Which Bind Cd22
  • Genetically Modified Human Natural Killer Cell Lines
  • Dna Encoding Antibody Molecules Which Bind Il-17a And Il-17f
  • Monoclonal Anti-Il-1racp Antibodies
  • Compositions And Methods For Detecting And Quantifying Host Cell Protein In Cell Lines And Recombinant Polypeptide Products
  • Human-Murine Chimeric Antibodies Against Respiratory Syncytial Virus
  • Zanamivir Phosphonate Congeners With Anti-Influenza Activity And Determining Oseltamivir Susceptibility Of Influenza Viruses
  • Adenovirus Isolated From Titi Monkeys
  • Methods For Treating Headache Using Antagonist Antibodies Directed Against Calcitonin Gene-Related Peptide
  • Rationally Designed, Synthetic Antibody Libraries And Uses Therefor
  • Antibodies Against Glucocorticoid-Induced Tumor Necrosis Factor Receptor (Gitr) And Uses Thereof
  • Anti-Trem2 Antibodies And Methods Of Use Thereof
  • Rsv Specific Binding Molecule
  • Production Of Anti-Self Antibodies From Antibody Segment Repertories And Displayed On Phage
  • Antibodies That Bind Il-4 And/Or Il-13 And Their Uses
  • Glycoengineered Binding Protein Compositions
  • Anti-Fzd10 Monoclonal Antibodies And Methods For Their Use
  • Anti-Ige Antibodies
  • Rsv-Specific Binding Molecule
  • Anti-Mesothelin Binding Proteins
  • Methods For Diagnosing And Treating Inflammatory Bowel Disease
  • Mutated Anti-Tnfα Antibodies And Methods Of Their Use
  • Treatment Of Allergic Diseases With Recombinant Antibodies
  • Use Of Anti-Cd83 Agonist Antibodies For Treating Autoimmune Diseases
  • Production Of Humanised Antibodies To Tnfα
  • Compositions And Methods For Treatment And Detection Of Cancers
  • Compositions And Methods In Cancer Associated With Altered Expression Of Prlr
  • Therapeutic Targets In Cancer
  • Methods For Treating Bone Cancer By Administering A Nerve Growth Factor Antagonist Antibody
  • Antibodies That Bind The Glutamate Ligand Binding Region Of Notch3
  • Non-Stochastic Generation Of Genetic Vaccines And Enzymes
  • Vegf/Dll4 Binding Agents And Uses Thereof
  • Methods For Treating Pain By Administering A Nerve Growth Factor Antagonist And An Nsaid
  • Antibodies Directed Against Amyloid-Beta Peptide
  • Nucleic Acid Molecules Encoding A Humanized Antibody
  • Isolated Polypeptides Of Cd44 And Uses Thereof
  • Monophosphorylated Lipid A Derivatives
  • Methods Of Treating Cardiovascular Disease With An Asgr Inhibitor
  • Methods And Compositions For Increasing Antibody Production
  • Anti-Sortilin Antibodies And Methods Of Use Thereof
  • Methods For Diagnosing And Treating Inflammatory Bowel Disease
  • Methods Of Treating Diabetes And Compositions Capable Of Same
  • Treatment Of Fibrosis With Il-11 Receptor Alpha Antibody
  • Separate-Cistron Contructs For Secretion Of Aglycosylated Antibodies From Prokaryotes
  • Methods And Compositions For Immuno-Histochemical Detection
  • Insulin Vitamin D Conjugates
  • Multispecific Antibodies
  • Heterodimeric Proteins
  • Ilt3 Binding Molecules And Uses Therefor
  • Nucleic Acids Coding For Antibodies Against Human Il-21 Receptor And Uses Therefor
  • Human Antibodies Specific For Tgfβ2
  • The Isolation And Production Of Catalytic Antibodies Using Phage Technology
  • Methods For Treating Rheumatoid Arthritis Using Human Antibodies That Bind Human Tnfα
  • Treating Headache Comprising Administering An Antibody To Calcitonin Gene-Related Peptide
  • Treatment Of Fibrosis With Interleukin-11 Antibody
  • Antibody Fragments Against The Insulin Receptor And Uses Thereof To Treat Hypoglycemia
  • Bispecific Anti-Vegf/Anti-Ang-2 Antibodies And Their Use In The Treatment Of Ocular Vascular Diseases
  • Methods And Compositions Of Matter Concerning April/G70, Bcma, Blys/Agp-3 And Taci
  • Monoclonal Antibodies Against Hmgb1
  • Human Monoclonal Anti-Pd-L1 Antibodies And Methods Of Use
  • Inhibitors Of The Interaction Between Hmgb Polypeptides And Toll-Like Receptor 2 As Anti-Inflammatory Agents
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  • Therapeutic Dll4 Binding Proteins
  • Compositions And Methods In Cancer Associated With Altered Expression Of Kcnj9
  • Therapeutic Dll4 Binding Proteins
  • Vegf/Dll4 Binding Agents And Uses Thereof
  • Humanized Antibodies Against Ceacam1
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  • Cell Culture Media And Methods Of Antibody Production
  • Anti-Cd33 Antibodies And Methods Of Use Thereof
  • Heterodimeric Human Igg1 Polypeptides With Isoelectric Point Modifications
  • Monoclonal Antibody 175 Targeting The Egf Receptor And Derivatives And Uses Thereof
  • Powdered Protein Compositions And Methods Of Making Same
  • Stirred Tank Bioreactor
  • Removal Of A-Scan Streaking Artifact
  • Multimodal Segmentation In Intravascular Images
  • System And Method For Graphical Processing Of Medical Data
  • High Affinity Antibodies Against Hmgb1 And Methods Of Use Thereof
  • Fusion Proteins For Treating Cancer And Related Methods
  • Exonuclease-Mediated Nucleic Acid Reassembly In Directed Evolution
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  • Signaling Conjugates And Methods Of Use
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  • Treatment Of Fibrosis With Interleukin-11 Antibody
  • Chimeric Fibroblast Growth Factors With Altered Receptor Specificity
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  • Method For Treating Joint Damage
  • Flavivirus Neutralizing Antibodies And Methods Of Use Thereof
  • Production Of Anti-Self Antibodies From Antibody Segment Repertoires And Displayed On Phage
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  • Antibodies That Bind To Mhc Class I Polypeptide-Related Sequence A
  • Improved Anti-Vegfr-2 Monoclonal Antibody
  • Dual Variable Domain Immunoglobulins And Uses Thereof
  • Rsv-Specific Binding Molecules And Means For Producing Them
  • Therapeutic Vitamin D Conjugates
  • Antigen Binding Constructs To Cd8
  • Il-I Binding Proteins
  • Composition And Method For The Diagnosis And Treatment Of Iron-Related Disorders
  • Method Of Treating An Ischemia-Reperfusion Injury-Related Disorder By Administering Gpcr Ligands
  • Anti-Rankl Antibodies And Methods Of Use
  • Methods For Chemically Synthesizing Immunoglobulin Chimeric Proteins
  • Reactive Labelling Compounds And Uses Thereof
  • Nucleic Acids Encoding, And Methods Of Producing, Antibodies Specific For Transforming Growth Factor (Tgf)-Β
  • Rapid And Sensitive Method For Detection Of Biological Targets
  • Modulated Lysine Variant Species Compositions And Methods For Producing And Using The Same
  • Biological Products
  • Method For Analyzing Proteins
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Method For Creating Polynucleotide And Polypeptide Sequences
  • Method For In Vitro Molecular Evolution Of Protein Function
  • Methods And Compositions For Cellular And Metabolic Engineering
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Bh3 Peptides And Methods Of Use Thereof
  • Cardiotrophin-1 Defective Mouse
  • Cardiotrophin-1 Compositions And Methods For The Treatment Of Tumor
  • Method For Analyzing Proteins
  • Method Of Improving Characteristics Of Proteins
  • Immunoglobulin Chimeric Monomer-Dimer Hybrids
  • Method For In Vitro Molecular Evolution Of Protein Function
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Directed Evolution Of Thermophilic Enzymes
  • Methods For Generating Polynucleotides Having Desired Characteristics By Iterative Selection And Recombination
  • Identification And Expression Of A Novel Kinesin Motor Protein
  • Libraries Of Genetic Packages Comprising Novel Hc Cdr3 Designs
  • Methods And Compositions For Cellular And Metabolic Engineering
  • Methods Of Producing Two Chain Proteins In Bacteria
  • Formulations With Reduced Oxidation
  • Method For Making Heteromultimeric Molecules
  • Methods And Compositions For Cellular And Metabolic Engineering
  • Quantification Of Single Target Molecules In Histological Samples
  • Immunoglobulin Chimeric Monomer-Dimer Hybrids
  • Production Of Proteins In Glutamine-Free Cell Culture Media
  • Methods For Modulating Protein Glycosylation Profiles Of Recombinant Protein Therapeutics Using Monosaccharides And Oligosaccharides
  • Low Acidic Species Compositions And Methods For Producing And Using The Same
  • Methods Of Improving Stem Cell Homing And Engraftment
  • Binding Domains Of Proteins Of The Repulsive Guidance Molecule (Rgm) Protein Family And Functional Fragments Thereof, And Their Use
  • Cytokine Receptor And Nucleic Acids Encoding The Same
  • Antibody To Gdf8 And Uses Thereof
  • Il-1 Binding Proteins
  • Catalytically Active Recombinant Memapsin And Methods Of Use Thereof
  • Il-1 Binding Proteins
  • Methods To Modulate Lysine Variant Distribution
  • Systems And Methods For Narrowing A Wavelength Emission Of Light
  • Low Acidic Species Compositions And Methods For Producing And Using The Same Using Displacement Chromatography
  • Elucidation Of Ion Exchange Chromatography Input Optimization
  • Novel Anti-Plasmodium Parasite Antibodies
  • Feeding Formula Appliance
  • Compositions And Methods For Treatment And Detection Of Cancers
  • Systems And Methods For Generating Images Of Tissue
  • Antibodies Recognizing A Carbohydrate Containing Epitope On Cd-43 And Cea Expressed On Cancer Cells And Methods Using Same
  • Multivalent Antibodies And Uses Therefor
  • Anti Ceacam1 Antibodies And Methods Of Using Same
  • Anti-Bv8 Antibodies And Uses Thereof
  • Dual Specific Binding Proteins Directed Against Il-13 And Il-17
  • Complement Factor H Antibodies
  • Rsv-Specific Binding Molecules And Means For Producing Them
  • Heterodimeric Proteins
  • Anti-Dll3 Antibody Drug Conjugates
  • Combination Therapies For Treatment Of Cancer
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  • Method Of Treatment Comprising Purified Recombinant Il-13 Antibody
  • Peptides Which Bind To G Protein-Coupled Receptors
  • Engineered Anti-Cd20 Antibody Fragments For In Vivo Targeting And Therapeutics
  • Antibodies Specific To Fcrn
  • High Affinity Antibodies Against Hmgb1 And Methods Of Use Thereof
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt0792-779

    DOI

    http://dx.doi.org/10.1038/nbt0792-779

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1007019873

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/1368267


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    25 schema:description Diverse antibody libraries can be displayed on the surface of filamentous bacteriophage, and selected by panning of the phage with antigen. This allows human antibodies to be made directly in vitro without prior immunization, thus mimicking the primary immune response1. Here we have improved the affinity of one such “primary” antibody by sequentially replacing the heavy and light chain variable (V) region genes with repertoires of V–genes (chain shuffling)2 obtained from unimmunized donors. For a human phage antibody for the hapten 2–phenyloxazol–5–one (phOx) (Kd=3.2×10−7 M), we shuffled the light chains and isolated an antibody with a 20 fold improved affinity. By shuffling the first two hypervariable loops of the heavy chain, we isolated an antibody with a further 15–fold improved affinity. The reshuffled antibody differed in five of the six hypervariable loops from the original antibody and the affinity for phOx (Kd=1.1×10−9 M) was comparable to that of mouse hybridomas from the tertiary immune response. Reshuffling offers an alternative to random point mutation for affinity maturation of human antibodies in vitro.
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