104 results about "Antibody Repertoire" patented technology

Compostions, kits and methods are provided for generating highly diverse libraries of proteins such as antibodies via homologous recombination in vivo, and screening these libraries against protein, peptide and nucleic acid targets using a two-hybrid method in yeast. The method for screening a library of tester proteins against a target protein or peptide comprises: expressing a library of tester proteins in yeast cells, each tester protein being a fusion protein comprised of a first polypeptide subunit whose sequence varies within the library, a second polypeptide subunit whose sequence varies within the library independently of the first polypeptide, and a linker peptide which links the first and second polypeptide subunits; expressing one or more target fusion proteins in the yeast cells expressing the tester proteins, each of the target fusion proteins comprising a target peptide or protein; and selecting those yeast cells in which a reporter gene is expressed, the expression of the reporter gene being activated by binding of the tester fusion protein to the target fusion protein.

Compositions, methods, and kits are provided for efficiently generating and screening a library of highly diverse protein complexes for their ability to bind to other proteins or oligonucleotide sequences. In one aspect of the invention, a library of expression vectors is provided for expressing the library of protein complexes. The library comprises a first nucleotide sequence encoding a first polypeptide subunit; and a second nucleotide sequence encoding a second polypeptide subunit. The first and second nucleotide sequences each independently varies within the library of expression vectors. In addition, the first and second polypeptide subunit are expressed as separate proteins which self-assemble to form a protein complex, such as a double-chain antibody fragment (dcFv or Fab) and a fully assembled antibody, in cells into which the library of expression vectors are introduced. The library of expression vectors can be efficiently generated in yeast cells through homologous recombination; and the encoded proteins complexes with high binding affinity to their target molecule can be selected by high throughput screening in vivo or in vitro.

A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain variable domains derived from a limited repertoire of human immunoglobulin light chain variable gene segments that comprise histidine modifications in their germline sequence. Methods of making non-human animals that express antibodies comprising histidine residues encoded by histidine codons introduced into immunoglobulin light chain nucleotide sequences are provided.

A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses a single light chain variable domain derived from a single rearranged light chain variable region gene in the germline of the non-human animal, wherein the single rearranged light chain variable region gene comprises a substitution of at least one non-histidine encoding codon with a histidine encoding codon. Methods of making non-human animals that express antibodies comprising a histidine-containing universal light chain are provided.

The invention relates to a platform technology for production of antigen binding polypeptides having specificity for a desired target antigen which is based on the conventional antibody repertoire of species in the family Camelidae, and to antigen binding polypeptides obtained using this technology platform. In particular, the invention provides an antigen binding polypeptide comprising a VH domain and a VL domain, wherein at least one hypervariable loop or complementarity determining region (CDR) in the VH domain or the VL domain is obtained from a VH or VL domain of a species in the family Camelidae.

Provided are methods for efficiently and comprehensively screening antibody repertoires from B cells to obtain and produce molecules with binding characteristics and functional activities for use in human therapy.

The invention discloses a phage display antibody library and five strains of screened antibodies capable of being combined with S protein of novel coronavirus SARS-CoV-2. Mutation is introduced into an ultra-variable region of an antibody variable region based on synthetic biology and a phage display technology, and a gene is transferred into escherichia coli, so that a synthetic antibody librarycontaining 108 kinds of antibodies is constructed; the phage display antibody library provided by the invention can perform screening to obtain the antibody with the specificity and the detection function, so that powerful resources of biological research and medical diagnosis are expanded; and the five strains of antibodies capable of being combined with the S protein of the novel coronavirus arefurther screened out and can be used for detecting the virus, part of the antibodies can block combination of the virus and cells, and the antibodies have the capacity of neutralizing novel coronavirus infectivity, can be used for preparing a novel coronavirus detection product, preparing a drug for inhibiting the novel coronavirus and preparing a pharmaceutical preparation for preventing or treating diseases caused by the novel coronavirus, and have a wide application prospect.

A phage display library of variable heavy domain (V_HH or VH) fragments (sdAb fragments) derived from the antibody repertoire of a non-immunized llama is disclosed. The sdAb fragments of the library are characterized by the absence of cysteine residues in complementarity determining regions (CDRs) and a very low presence of residues of glutamic acid, arginine and glycine at positions 44, 45 and 47, respectively, of the VL interface of the variable heavy domain V_HH. The large size of the library (in the order of 10⁹) makes it a source of antigen-binding fragments having high affinity to almost any antigen of interest. The library is preferably generated using a modified fd-tet phage growing in plaques in the absence of a tetracycline.

The invention relates to a phage antibody library which assembles an ScFv gene fragment between Restriction Enzyme cutting sites of SfiI and NotI of a pCANTAB5E carrier. The phage antibody library is characterized in that the ScFv gene fragment can be affinitive and enriched with antigens of 16-membered macrolide agricultural chemicals to form a soluble single-chain antibody and the phage antibody library is applied to immunoassay of pesticide residue. The phage antibody library has the advantages that the antibody with high affinity can be obtained without animal immunization, the test period is short, the antibody library is the phage antibody library which takes small molecular milbemycin oxime of a 16-membered macrolide generic structure as immunogen to construct, the antibody library theoretically can directly obtain a specific antibody library of 16-membered macrolide compound through screening, the screening flux is high, the efficiency is high, the specificity is strong, and the affinity selecting range is wide, so that the phage antibody library has wide application prospect in the aspects such as agricultural chemical antibody preparation, testing technique development and the like.

The invention provides the technical field of antibody medicine, discloses a fully-humanized human anti-IL-1beta monoclonal antibody screened through the phage antibody library technology and prepared through the genetic engineering technology, and discloses a DNA molecule for encoding the monoclonal antibody, a DNA molecule expression carrier for encoding the monoclonal antibody, a host cell and application. The anti-IL-1beta monoclonal antibody can prevent bonding of human IL-1beta and human IL-1R. By means of bonding of IL-1beta, blocking of IL-1beta and a receptor signal channel of the IL-1beta, unnecessary IL-1beta initial induced heat transfer, amplified lymphocyte responses and stimulation acute stage responses can be reduced. The anti-IL-1beta monoclonal antibody can be used for detecting IL-1beta expressions and used for prevention and treatment of cryopyrin-associated periodic syndromes.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Igα and/or Igβ sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Igα and/or Igβ sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Igα and/or Igβ results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

A process for preparing an antigen microarray based on self antibody repertoire includes pre-treating substrate for adapting molecular self-assembly, generating a layer of agarose gel moleculae, chemical modifying it, designing antigen microarray, preparing antigen microarray by applying different biomacromolecular antigens on the surface of said substrate, and testint the chip by use of microscope or fluorescent scan to acquire the information about specimen. Its test method includes culturing the said microarray chip and specimen to be tested in warmhouse, hybridization with the second antigen probe of three fluorescein labels, and acquiring the information about specimen by multi-channel fluorescent scan.

The invention discloses a complete humanized antibody which is selected from humanized high-capacity phage antibody library and is high-affinity-combined with phosphatidylinositol proteoglycan 3. The invention includes a selection method of the antibody, an antibody coding sequence and corresponding amino acid residue sequence, and especially includes three CDR-zone sequences respectively at a heavy chain and a light chain, combination characters of an antigen and the construction method of the complete antibody. The antibody is a complete humanized antibody, is used for treatment in human body, is low in immunogenicity, is less in toxic and side effects, and has a potential value of treating liver cancer and melanin tumor.

The invention belongs to the technical field of genetic engineering, and discloses a canine-derived anti-canine parvovirus antibody, an antibody library and a construction method thereof. The canine-derived anti-canine parvovirus antibody is a heavy chain variable region with an amino acid sequence of SEQ ID NO: 1 or a light chain variable region with an amino acid sequence of SEQ ID NO: 2. The nucleotide sequence of DNA molecule of the heavy chain variable region is SEQ ID NO: 3. The nucleotide sequence of DNA molecule of the light chain variable region is SEQ ID NO: 4. Compared with a monoclonal antibody produced by immune animals, the phage display technology of the invention has the advantages of fast production, simple operation and higher efficiency, can be adopted to produce canine-derived antibodies, and has higher utilization value. According to the invention, by constructing the phage display antibody library, the process of antibody generation can be simulated in vitro, andantibodies against any antigen can be screened.

This invention relates to an in vitro method of producing antigen specific B cells and antibodies that provides for the capture of an entire primary human antibody repertoire for any foreign antigen, allows for screening large numbers of immunogen/adjuvant combinations, and permits the isolation of human monoclonal antibodies on demand thereby obviating the need to immunize humans with the target antigen.