Provided herein are IL- 18 polypeptide variants that have binding specificity for the IL- 18 receptor. Also provided herein are fusion proteins, and conjugates comprising the IL- 18 polypeptide variants.
Provided herein are IL- 18 polypeptide prodrugs comprising IL- 18, a half-life extension element, an IL- 18 blocking element and a protease cleavable linker. Also provided herein are phannaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors, host cells for making such polypeptide prodrugs. Also disclosed are methods of using the polypeptide prodrugs in the treatment of diseases, conditions and disorders.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
3.
VARIANT CH3 DOMAINS ENGINEERED FOR PREFERENTIAL CH3 HETERODIMERIZATION, MULTI-SPECIFIC ANTIBODIES COMPRISING THE SAME, AND METHODS OF MAKING THEREOF
Variant CH3 domain polypeptides are provided that preferentially form CH3-CH3 heterodimers over CH3-CH3 homodimers. Such variant CH3 domains can be used to promote desired Fc pairing, thus providing for efficient development of bispecific and multispecific antibodies as well as Fc fusions of different formats. Methods of producing bispecific antibodies using such variant CH3 domains and for producing libraries containing such variant CH3 domains are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
C40B 40/10 - Libraries containing peptides or polypeptides, or derivatives thereof
4.
VARIANT CH3 DOMAINS ENGINEERED FOR PREFERENTIAL CH3 HETERODIMERIZATION, MULTI-SPECIFIC ANTIBODIES COMPRISING THE SAME, AND METHODS OF MAKING THEREOF
Variant CH3 domain polypeptides are provided that preferentially form CH3-CH3 heterodimers over CH3-CH3 homodimers. Such variant CH3 domains can be used to promote desired Fc pairing, thus providing for efficient development of bispecific and multispecific antibodies as well as Fc fusions of different formats. Methods of producing bispecific antibodies using such variant CH3 domains and for producing libraries containing such variant CH3 domains are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity.
Presented herein are systems and methods for constructing antibody libraries using machine learning to inform sequence selection for inclusion in the library. The techniques include (i) the training and use of machine learning models and statistical models to predict biophysical and biochemical properties from sequences, and (ii) the training and use of machine learning models for predicting developability from sequences, and for generating novel sequences. In certain embodiments, the systems and methods generate libraries of antibodies (and/or antibody-encoding polynucleotides) by specifically designing the libraries with directed sequence and/or length diversity. The resulting libraries are useful, for example, in the development of therapeutic agents.
Provided herein are antibody agents that bind specifically to Activin A, as well as compositions comprising Activin A antibody agents, and methods of making and using the same.
Provided herein are antibody agents that bind specifically to GDF15, as well as compositions comprising GDF15 antibody agents, and methods of making and using the same.
The present disclosure relates to anti-idiotypic antibodies binding to anti-CD3 antibodies, and uses thereof, e.g., in assays and methods of treatment.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 25/00 - Drugs for disorders of the nervous system
The present disclosure includes anti-CD3 binding domains and antibodies and/or antigen-binding fragments including such domains. Also included are multispecific antibodies and antibody fragments. The present disclosure further includes nucleic acids and vectors encoding such antibodies or antibody fragments and cells comprising such nucleic acids. Further included are pharmaceutical compositions, in vivo methods, and manufacturing methods relating to anti-CD3 antibodies or antigen-binding fragments.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
THE GOVERNMENT OF THE UNITED STATES, AS REPRESENTED BY THE SECRETARY OF THE ARMY (USA)
Inventor
Walker, Laura M.
Wec, Anna Z.
Guardado-Calvo, Pablo
Rey, Felix A.
Mittler, Eva
Chandran, Kartik
Bradfute, Steven B.
Abelson, Dafna M.
Herbert, Andrew S.
Dye, John
Abstract
Provided herein are hantivirus antibodies. These hantivirus antibodies bind to the Gn and/or Gc subunits of a hantavirus glycoprotein and have broad neutralizing activity against an epitope of different hantavirus species. Such antibodies are used in methods of inducing an immune response and methods of inhibiting hantavirus infection. Additionally provided are methods of treating an infectious disease using such antibodies.
Variant CH1 domains, variant CL domains, and variant CH1-CL domain sets which contain at least one amino acid substitution that promotes preferential CH1-CL pairing are provided. Also provided are polypeptides, molecules, and multi-specific antibodies comprising such variants; and compositions comprising any of the foregoing. Methods of generating a variant CH1 and/or variant CL domain library and methods of using same to identify one or more variant CH1 and/or variant CL domains and/or variant CH1-CL domain sets are also provided. Further provided are methods of screening for a combination of CH1-CL sets suited for multi-specific antibodies and/or antigen-binding antibody fragments.
Provided herein are antibody agents that bind specifically to Activin-A and Activin- B, as well as compositions comprising Activin A/B antibody agents, and methods of making and using the same.
A61P 5/50 - Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
A61P 13/00 - Drugs for disorders of the urinary system
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
15.
PH-DEPENDENT ANTI-CD3 ANTIBODIES AND METHODS RELATING THERETO
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
16.
RATIONALLY DESIGNED, SYNTHETIC ANTIBODY LIBRARIES AND USES THEREFOR
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity. The libraries are designed to reflect the preimmune repertoire naturally created by the human immune system and are based on rational design informed by examination of publicly available databases of human antibody sequences.
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity. The libraries are designed to reflect the preimmune repertoire naturally created by the human immune system, with or without DH segments derived from other species, and are based on rational design informed by examination of publicly available databases of antibody sequences.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as nucleic acid sequences encoding such antibodies, methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
CH1 domain variants engineered for preferential binding to either a kappa CL domain or a lambda CL domain, as well as polypeptides, e.g., antibody heavy chains or antibodies, comprising such engineered CH1 domain variants, and pharmaceutical compositions comprising such CH1 domain variants and/or such polypeptides, and methods for making and using such CH1 domain variants are provided. The CH1 domain variants minimize heavy chain-light chain mispairing and promote cognate heavy chain-light chain pairing, thereby improving the generation of multispecific, e.g., bispecific, antibodies. Also provided are methods of making CH1 domain variant libraries and methods of identifying one or more CH1 domain variants.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
Provided herein are antibody agents that bind specifically to Activin A, as well as compositions comprising Activin A antibody agents, and methods of making and using the same.
Variant CH3 domain polypeptides are provided that preferentially form CH3-CH3 heterodimers over CH3-CH3 homodimers. Such variant CH3 domains can be used to promote desired Fc pairing, thus providing for efficient development of bispecific and multispecific antibodies as well as Fc fusions of different formats. Methods of producing bispecific antibodies using such variant CH3 domains and for producing libraries containing such variant CH3 domains are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
Provided herein are methods of treating and/or preventing certain types and/or instances of nausea and/or emesis with which it had not previously been considered to be associated, by targeting the GDF15-GFRAL pathway.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
The present disclosure relates to anti-idiotypic antibodies binding to anti-CD3 antibodies, and uses thereof, e.g., in assays and methods of treatment.
Anti-CD3 binding domains and antibodies comprising them, including multispecific antibodies, with, inter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use. Reagents for identifying, isolating, selecting, generating and characterizing CD3 binding domains and antibodies comprising them are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
27.
SYSTEMS AND METHODS FOR INTELLIGENT CONSTRUCTION OF ANTIBODY LIBRARIES
Presented herein are systems and methods for constructing antibody libraries using machine learning to inform sequence selection for inclusion in the library. The techniques include (i) the training and use of machine learning models and statistical models to predict biophysical and biochemical properties from sequences, and (ii) the training and use of machine learning models for predicting developability from sequences, and for generating novel sequences. In certain embodiments, the systems and methods generate libraries of antibodies (and/or antibody-encoding polynucleotides) by specifically designing the libraries with directed sequence and/or length diversity. The resulting libraries are useful, for example, in the development of therapeutic agents.
Presented herein are systems and methods for constructing antibody libraries using machine learning to inform sequence selection for inclusion in the library. The techniques include (i) the training and use of machine learning models and statistical models to predict biophysical and biochemical properties from sequences, and (ii) the training and use of machine learning models for predicting developability from sequences, and for generating novel sequences. In certain embodiments, the systems and methods generate libraries of antibodies (and/or antibody-encoding polynucleotides) by specifically designing the libraries with directed sequence and/or length diversity. The resulting libraries are useful, for example, in the development of therapeutic agents.
Provided herein are antibody agents that bind specifically to Activin A, as well as compositions comprising Activin A antibody agents, and methods of making and using the same.
Provided herein are antibody agents that bind specifically to Activin A, as well as compositions comprising Activin A antibody agents, and methods of making and using the same.
The present disclosure includes anti-CD3 binding domains and antibodies and/or antigen-binding fragments including such domains. Also included are multispecific antibodies and antibody fragments. The present disclosure further includes nucleic acids and vectors encoding such antibodies or antibody fragments and cells comprising such nucleic acids. Further included are pharmaceutical compositions, in vivo methods, and manufacturing methods relating to anti-CD3 antibodies or antigen-binding fragments.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure includes anti-CD3 binding domains and antibodies and/or antigen-binding fragments including such domains. Also included are multispecific antibodies and antibody fragments. The present disclosure further includes nucleic acids and vectors encoding such antibodies or antibody fragments and cells comprising such nucleic acids. Further included are pharmaceutical compositions, in vivo methods, and manufacturing methods relating to anti-CD3 antibodies or antigen-binding fragments.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
33.
Polyclonal mixtures of antibodies, and methods of making and using them
A method of broadening epitopic coverage of an antigen of interest, wherein a first sample of the antigen of interest is contacted with a first plurality of host cells collectively expressing a first library of antibodies. Host cells expressing antibodies that bind to the antigen are then collected from among the first plurality of host cells, and a composition is prepared comprising a polyclonal mixture of antibodies expressed by these host cells. A second sample of the antigen of interest is then contacted with an aliquot of the prepared composition and a second plurality of host cells collectively expressing a second library of antibodies. Host cells expressing antibodies that bind to the second sample of the antigen are then collected from among the second plurality of host cells.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
34.
ANTI-GDF15 ANTIBODIES, COMPOSITIONS AND USES THEREOF
Provided herein are antibody agents that bind specifically to GDF15, as well as compositions comprising GDF15 antibody agents, and methods of making and using the same.
Provided herein are antibody agents that bind specifically to GDF15, as well as compositions comprising GDF15 antibody agents, and methods of making and using the same.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Antibodies and antigen-binding fragments thereof with high affinity for CD3 and desirable developability profiles are provided, as well as methods for their manufacture and use.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present invention provides Fc variants and polypeptides, e.g., antibodies and Fc fusion proteins, comprising such Fc variants. In particular, Fc variants with diminished effector function as a consequence of hinge region and CH2 domain mutations, e.g., LALE-PG, are provided. Such variants maintain antigen-binding and favorable developability profiles and may display improved expressability.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
39.
ENGINEERED PH-DEPENDENT ANTI-CD3 ANTIBODIES, AND METHODS FOR THEIR GENERATION AND USE
Engineered pH-dependent anti-CD3 binding domains and antibodies and/or antigen-binding domains comprising same, including multispecific antibodies, with, inter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
40.
LTBP complex-specific inhibitors of TGFβ and uses thereof
Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGFβ and/or LTBP3-TGFβ. The application also provides methods of use of these inhibitors for, for example, inhibiting TGFβ activation, and treating subjects suffering from TGFβ-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGFβ inhibitor for a subject in need thereof are also provided.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
41.
VARIANT CH3 DOMAINS ENGINEERED FOR PREFERENTIAL CH3 HETERODIMERIZATION, MULTI-SPECIFIC ANTIBODIES COMPRISING THE SAME, AND METHODS OF MAKING THEREOF
Variant CH3 domain polypeptides are provided that preferentially form CH3-CH3 heterodimers over CH3-CH3 homodimers. Such variant CH3 domains can be used to promote desired Fc pairing, thus providing for efficient development of bispecific and multispecific antibodies as well as Fc fusions of different formats. Methods of producing bispecific antibodies using such variant CH3 domains and for producing libraries containing such variant CH3 domains are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C40B 40/10 - Libraries containing peptides or polypeptides, or derivatives thereof
42.
VARIANT CH1 DOMAINS AND VARIANT CL DOMAINS ENGINEERED FOR PREFERENTIAL CHAIN PAIRING AND MULTI-SPECIFIC ANTIBODIES COMPRISING THE SAME
Variant CH1 domains, variant CL domains, and variant CH1-CL domain sets which contain at least one amino acid substitution that promotes preferential CH1-CL pairing are provided. Also provided are polypeptides, molecules, and multi-specific antibodies comprising such variants; and compositions comprising any of the foregoing. Methods of generating a variant CH1 and/or variant CL domain library and methods of using same to identify one or more variant CH1 and/or variant CL domains and/or variant CH1-CL domain sets are also provided. Further provided are methods of screening for a combination of CH1-CL sets suited for multi-specific antibodies and/or antigen-binding antibody fragments.
Variant CH3 domain polypeptides are provided that preferentially form CH3-CH3 heterodimers over CH3-CH3 homodimers. Such variant CH3 domains can be used to promote desired Fc pairing, thus providing for efficient development of bispecific and multispecific antibodies as well as Fc fusions of different formats. Methods of producing bispecific antibodies using such variant CH3 domains and for producing libraries containing such variant CH3 domains are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C40B 40/10 - Libraries containing peptides or polypeptides, or derivatives thereof
44.
VARIANT CH1 DOMAINS AND VARIANT CL DOMAINS ENGINEERED FOR PREFERENTIAL CHAIN PAIRING AND MULTI-SPECIFIC ANTIBODIES COMPRISING THE SAME
Variant CH1 domains, variant CL domains, and variant CH1-CL domain sets which contain at least one amino acid substitution that promotes preferential CH1-CL pairing are provided. Also provided are polypeptides, molecules, and multi-specific antibodies comprising such variants; and compositions comprising any of the foregoing. Methods of generating a variant CH1 and/or variant CL domain library and methods of using same to identify one or more variant CH1 and/or variant CL domains and/or variant CH1-CL domain sets are also provided. Further provided are methods of screening for a combination of CH1-CL sets suited for multi-specific antibodies and/or antigen-binding antibody fragments.
Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGFβ and/or LTBP3-TGFβ. The application also provides methods of use of these inhibitors for, for example, inhibiting TGFβ activation, and treating subjects suffering from TGFβ-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGFβ inhibitor for a subject in need thereof are also provided.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
46.
ANTI-CRIMEAN-CONGO HEMORRHAGIC FEVER VIRUS ANTIBODIES, AND METHODS OF THEIR GENERATION AND USE
Anti-CCHFV antibodies with neutralizing potency and protective efficacy against CCHFV are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
C12N 15/52 - Genes encoding for enzymes or proenzymes
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
A61K 39/00 - Medicinal preparations containing antigens or antibodies
48.
Polyspecificity reagents, methods for their preparation and use
The present invention relates, inter alia, to polyspecificity reagents, methods of making the same, and methods of using the same in, inter alia, the selection, screening, enrichment, and identification of non-polyspecific, and thus developable, polypeptides.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity.
CH1 domain variants engineered for preferential binding to either a kappa CL domain or a lambda CL domain, as well as polypeptides, e.g., antibody heavy chains or antibodies, comprising such engineered CH1 domain variants, and pharmaceutical compositions comprising such CH1 domain variants and/or such polypeptides, and methods for making and using such CH1 domain variants are provided. The CH1 domain variants minimize heavy chain-light chain mispairing and promote cognate heavy chain-light chain pairing, thereby improving the generation of multispecific, e.g., bispecific, antibodies. Also provided are methods of making CH1 domain variant libraries and methods of identifying one or more CH1 domain variants.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
51.
CH1 DOMAIN VARIANTS ENGINEERED FOR PREFERENTIAL LIGHT CHAIN PAIRING AND MULTISPECIFIC ANTIBODIES COMPRISING THE SAME
CH1 domain variants engineered for preferential binding to either a kappa CL domain or a lambda CL domain, as well as polypeptides, e.g., antibody heavy chains or antibodies, comprising such engineered CH1 domain variants, and pharmaceutical compositions comprising such CH1 domain variants and/or such polypeptides, and methods for making and using such CH1 domain variants are provided. The CH1 domain variants minimize heavy chain-light chain mispairing and promote cognate heavy chain-light chain pairing, thereby improving the generation of multispecific, e.g., bispecific, antibodies. Also provided are methods of making CH1 domain variant libraries and methods of identifying one or more CH1 domain variants.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61P 43/00 - Drugs for specific purposes, not provided for in groups
The present invention provides Fc variants and polypeptides, e.g., antibodies and Fc fusion proteins, comprising such Fc variants. In particular, Fc variants with diminished effector function as a consequence of hinge region and CH2 domain mutations, e.g., LALE-PG, are provided. Such variants maintain antigen-binding and favorable developability profiles and may display improved expressability.
Methods for purifying multispecific antibodies on interest (MAIs) that co-engage at least two different antigens or epitopes (also referred to targets, used interchangeably throughout), from compositions comprising the MAI and parental homodimeric antibody species are provided, as well as reagents which may be used to practice such methods.
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
B01J 39/26 - Cation exchangers for chromatographic processes
B01J 41/20 - Anion exchangers for chromatographic processes
54.
LTBP complex-specific inhibitors of TGFβ and uses thereof
Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGFβ and/or LTBP3-TGFβ. The application also provides methods of use of these inhibitors for, for example, inhibiting TGFβ activation, and treating subjects suffering from TGFβ-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGFβ inhibitor for a subject in need thereof are also provided.
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
55.
ENGINEERED PH-DEPENDENT ANTI-CD3 ANTIBODIES, AND METHODS FOR THEIR GENERATION AND USE
Engineered pH-dependent anti-CD3 binding domains and antibodies and/or antigen-binding domains comprising same, including multispecific antibodies, with, inter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
inter aliainter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
57.
HIGH AFFINITY ANTI-CD3 ANTIBODIES, AND METHODS FOR THEIR GENERATION AND USE
Antibodies and antigen-binding fragments thereof with high affinity for CD3 and desirable developability profiles are provided, as well as methods for their manufacture and use.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Antibodies and antigen-binding fragments thereof with high affinity for CD3 and desirable developability profiles are provided, as well as methods for their manufacture and use.
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
This disclosure provides ALK7-binding proteins such as anti-ALK7 antibodies, and compositions and methods for making the ALK7-binding proteins. In certain embodiments, the ALK7-binding proteins inhibit or antagonize ALK7 activity. In addition, the disclosure provides compositions and methods for diagnosing and treating overweight, obesity, diabetes, overweight, obesity, type 2 diabetes, and their associated conditions; metabolic disorders, and other diseases or conditions that can be treated, prevented or ameliorated by targeting ALK7.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially, similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially, similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
A method of broadening epitopic coverage of an antigen of interest, wherein a first sample of the antigen of interest is contacted with a first plurality of host cells collectively expressing a first library of antibodies. Host cells expressing antibodies that bind to the antigen are then collected from among the first plurality of host cells, and a composition is prepared comprising a polyclonal mixture of antibodies expressed by these host cells. A second sample of the antigen of interest is then contacted with an aliquot of the prepared composition and a second plurality of host cells collectively expressing a second library of antibodies. Host cells expressing antibodies that bind to the second sample of the antigen are then collected from among the second plurality of host cells.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Multispecific antibody analogs that co-engage at least two different antigens or epitopes, which may also be referred to as targets as used interchangeably throughout, said analogs comprising a common light chain, are provided, as well as methods for their production and use.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure relates to anti-IL-27 antibodies, and antigen-binding portions thereof. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the antibodies or antigen-binding portion thereof. The disclosure also relates to methods for detecting IL-27 in, for example, a subject or a sample.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
Anti-CD3 binding domains and antibodies comprising them, including multispecific antibodies, with, inter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use. Reagents for identifying, isolating, selecting, generating and characterizing CD3 binding domains and antibodies comprising them are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
74.
ANTI-HLA-G ANTIBODIES, COMPOSITIONS COMPRISING ANTI-HLA-G ANTIBODIES AND METHODS OF USING ANTI-HLA-G ANTIBODIES
Provided herein are antibodies that selectively bind to HLA-G and and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Multi-specific binding proteins that bind BCMA, the NKG2D receptor, and CD 16 are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure relates to anti-IL-27 antibodies, and antigen-binding portions thereof. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the antibodies or antigen-binding portion thereof. The disclosure also relates to methods for detecting IL-27 in, for example, a subject or a sample.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
The present disclosure relates to anti-IL-27 antibodies, and antigen-binding portions thereof. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the antibodies or antigen-binding portion thereof. The disclosure also relates to methods for detecting IL-27 in, for example, a subject or a sample.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
80.
Anti-respiratory syncytial virus antibodies, and methods of their generation and use
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as nucleic acid sequences encoding such antibodies, methods for their identification, isolation, generation, and methods for their preparation and use are provided.
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity. The libraries are designed to reflect the preimmune repertoire naturally created by the human immune system and are based on rational design informed by examination of publicly available databases of human antibody sequences.
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity. The libraries are designed to reflect the preimmune repertoire naturally created by the human immune system, with or without DH segments derived from other species, and are based on rational design informed by examination of publicly available databases of antibody sequences.
This disclosure provides ALK7-binding proteins such as anti-ALK7 antibodies, and compositions and methods for making the ALK7-binding proteins. In certain embodiments the ALK7-binding proteins inhibit, or antagonize ALK7 activity. In addition, the disclosure provides compositions and methods for diagnosing and treating overweight, obesity, diabetes, overweight, obesity, type 2 diabetes, and their associated conditions; metabolic disorders, and other diseases or conditions that can be treated, prevented or ameliorated by targeting ALK7.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Provided are antibodies or antigen binding polypeptides characterized by the ability to neutralize respiratory syncytial virus (RSV). Specifically, the antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV fusion glycoprotein (RSVF). Further provided are methods for their identification, isolation, generation, preparation, and use, as well as the heavy chain and light chain sequences of the antibodies provided.
The present invention relates, inter alia, to polyspecificity reagents, methods of making the same, and methods of using the same in, inter alia, the selection, screening, enrichment, and identification of non-polyspecific, and thus developable, polypeptides.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
The present invention overcomes the inadequacies inherent in the known methods for generating libraries of antibody-encoding polynucleotides by specifically designing the libraries with directed sequence and length diversity.
Anti-CD3 binding domains and antibodies comprising them, including multispecific antibodies, with, inter alia, desirable T-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use. Reagents for identifying, isolating, selecting, generating and characterizing CD3 binding domains and antibodies comprising them are also provided.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
88.
ANTI-CD3-BINDING DOMAINS AND ANTIBODIES COMPRISING THEM, AND METHODS FOR THEIR GENERATION AND USE
Anti-CD3 binding domains and antibodies comprising them, including multispecific antibodies, with, inter alia, desirableT-cell activation and (re)directed target cell killing potency and developability, profiles are provided, as well as methods for their identification, isolation, and generation, and methods for their preparation and use. Reagents for identifying, isolating, selecting, generating and characterizing CD3 binding domains and antibodies comprising them are also provided.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Described herein are compositions and methods for the prevention and treatment of ebolavirus infection. In certain embodiments of the present invention, monoclonal antibodies substantially similar to those described herein, as well as affinity matured variants thereof, alone or in combination, provide therapeutic efficacy in a patient against multiple species of ebolavirus.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as nucleic acid sequences encoding such antibodies, methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Anti-RSV antibodies with neutralizing potency against RSV subtype A and RSV subtype B are provided, as well as methods for their identification, isolation, generation, and methods for their preparation and use are provided.
Methods for purifying multispecific antibodies on interest (MAIs) that co-engage at least two different antigens or epitopes (also referred to targets, used interchangeably throughout), from compositions comprising the MAI and parental homodimeric antibody species are provided, as well as reagents which may be used to practice such methods.
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
B01J 39/26 - Cation exchangers for chromatographic processes
B01J 41/20 - Anion exchangers for chromatographic processes
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
A61K 39/00 - Medicinal preparations containing antigens or antibodies
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.
C07K 16/40 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against enzymes
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 39/00 - Medicinal preparations containing antigens or antibodies
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
