91 results about "Affinity maturation" patented technology

The present invention relates to anti-FcRH5 antibodies, including anti-FcRH5 antibodies comprising an FcRH5 binding domain and a CD3 binding domain (e.g., FcRH5 T cell-dependent bispecific (TDB) antibodies), and methods of using the same.

A method for detecting dynamic gridding instruction based on artificial immunity, is a method for detecting instruction facing to gridding which takes use the artificial immunity technique for reference. According to the dynamic and real time requirement of the instruction detection under gridding surroundings, the method takes the prior clonal selection algorithm as main body, combines negative selection, clonal selection, affinity maturation and memory detector gene bank method, so at to dynamic handle the instruction detection under gridding surroundings. The method includes a dynamic detector evolvement process and a gridding instruction detection process which are based on artificial immunity, which is characterized in by using the artificial immunity technique for reference, and combining the negative selection, clonal selection, affinity maturation and memory detector gene bank method; firstly obtaining an evolvement matured detector; and then dynamically handling the instruction detection problem in the gridding surroundings under the coordination of the artificial immunity mechanism, to complete the entire process of dynamic gridding instruction detection.

The present invention relates to methods for engineering VH domains to improve their solubility and stability. The invention provides for the incorporation of defined amino acid substitutions based on 3-D structural information into the V segments of a heavy chain locus, expressing the locus in a non-human mammal and selecting soluble VH domains. Further stabilising or solubilising mutations maybe introduced as a result affinity maturation during B-cell maturation in vivo.

The present invention relates to an anti-idiotypic polypeptide scaffold that includes two or more peptide sequences that mimic a discontinuous epitope of a pathogen that is recognized by or induces formation of a broadly neutralizing antibody. Using a fibronectin FNfn10 scaffold bearing two or more modified discontinuous loops, scaffolds that recognize broadly neutralizing antibodies in vitro and from patient serum have been identified. These scaffolds should induce an immune response or mobilize germline specificities to initiate their affinity maturation.

The invention relates, in one aspect, generally to novel concept of guided selection of antibody variable domains, combination and expression entirely in vivo. An application is to produce multivalent polypeptides. The present invention relates to multivalent (eg, multispecific) antibodies, antibody chains and polypeptides, as well as heavy chain-only antibodies (H2 antibodies) that are devoid of light chains. The invention further relates to the selection, maturation and production of these in vivo in non-human vertebrates and non-human vertebrate cells. To this end the invention also relates to such non-human vertebrates and cells. The invention also relates to the provision of means to produce and select heavy chain-only antibodies and heavy chains comprising variable domains that have undergone affinity maturation.

The present invention relates to a method for adjusting the affinity of a polypeptide to a target molecule by a combination of steps, including: (1) the identification of aspartyl residues which are prone to isomerization; (2) the substitution of alternative residues and screening the resulting mutants for affinity against the target molecule. In a preferred embodiment, the method of subtituting residues is affinity maturation with phage display (AMPD). In a further preferred embodiment the polypeptide is an antibody and the target molecule is an antigen. In a further preferred embodiment, the antibody is anti-IgE and the target molecule is IgE. In another embodiment, the invention relates to an anti-IgE antibody having improved affinity to IgE.

This invention provides methods of obtaining a binding molecule, e.g., an antibody, that has enhanced affinity for a binding partner relative to a reference binding molecule.

The invention belongs to the biotechnical field, and concretely relates to a recombinant humanized anti-PD-1 and c-MET bispecific antibody, and a preparation method and an application thereof. Humanized antibody database comparison, computer molecular structure simulation, molecular docking simulation and sequence analysis are carried out, and recombinant humanized anti-PD-1 and c-MET bispecific antibody molecule designing comprising affinity maturation, structure optimization, humanization and codon optimization is carried out, and an expression plasmid of the recombinant humanized anti-PD-1 and c-MET bispecific antibody is constructed on the basis of an optimized signal peptide sequence and a plasmid expression vector replicon. The bispecific antibody has the characteristics of low immunogenicity, simple and safe preparation process, high yield, high purity and high activity, and can be used to further prepare new specific drugs for treating non-small cell lung cancer.

The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.

The present invention concerns a means for obtaining cells which produce human, humanized or chimeric antibodies in commercially useful quantities. The invention permits high antibody producer cells to be selected and isolated from animals for use in culture to produce antibodies. The invention also provides methods for the affinity maturation of human, humanized or chimeric immunoglobulins.

Compositions, methods, and kits are provided for efficiently generating and screening humanized antibody with high affinity against a specific antigen. The library of humanized antibody is generated by mutagenizing a chimeric antibody template that combines human antibody framework and antigen binding sites of a non-human antibody. Alternatively, the library of humanized antibody is generated by grafting essential antigen-recognition segment(s) such as CDRs of the non-human antibody into the corresponding position(s) of each member of a human antibody library. This library of humanized antibody is then screened for high affinity binding toward a specific antigen in vivo in organism such as yeast or in vitro using techniques such as ribosome display or mRNA display. The overall process can be efficiently performed in a high throughput and automated manner, thus mimicking the natural process of antibody affinity maturation.

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.

In order to provide a antibody against hIL-33 with clinical application prospect, the invention provides a high-affinity mouse anti-human IL-33 antibody by adopting a panning technology of immunizingmouse B cells, based on the action mechanism of IL-33 in inflammation and tumors in the prior art, the function of IL-33 in regulating cytokine secretion, and cytokines involved in inflammation and tumors. After recombinant expression of mouse-derived antibodies, preliminary screening of biological activity, humanization transformation, affinity maturation and biological activity rescreening, a humanized monoclonal antibody against hIL-33 is obtained, and the monoclonal antibody has the characteristics of high stability, high affinity, good biological activity, broad clinical application prospects, etc.

The invention relates to the technical field of biotechnology and particularly relates to an anti-CD19 antibody and a preparation method and use thereof. The anti-CD19 antibody comprises a heavy chainvariable region and a light chain variable region. The complementarity determining region of the heavy chain variable region comprises CDR-H1 with an amino acid sequence shown in the formula of SEQ ID No. 1, CDR-H2 with an amino acid sequence shown in the formula of SEQ ID No. 2 and CDR-H3 with an amino acid sequence shown in the formula of SEQ ID No. 3. The complementarity determining region ofthe light chain variable region comprises CDR-L1 with an amino acid sequence shown in the formula of SEQ ID No. 4, CDR-L2 with an amino acid sequence shown in the formula of SEQ ID No. 5, No. 6 or No.7 and CDR-L3 with an amino acid sequence shown in the formula of SEQ ID No. 8. The FMC63 scFv is screened in affinity maturation through a phage display technology so that a high affinity single chain antibody against CD19 is obtained.

The present invention is directed to recombinant human antibodies specific for Cn2 toxin from C. noxius scorpion venom. The antibodies are able to recognize the toxin and preferably neutralize it as well as the whole venom of C. noxius scorpion. This invention is also directed to a human non-immune phage display library. One clone that specifically binds the Cn2 toxin was affinity matured by directed evolution. Three cycles of maturation were performed and several scFv clones were isolated which specifically recognize toxin Cn2 with increased K_d of 446 fold. All variants were monomeric and only variants 6009F, 6105F and 6103E showed to be capable of neutralizing toxin Cn2 and the whole venom. Variant 6009F recognizes a different epitope than that of BCF2, a murine monoclonal antibody raised against scorpion toxin Cn2 which is also capable of neutralizing both Cn2 toxin and the whole venom when tested in mice, as well as that of commercially available polyclonal antibody fragments antivenom from horse. The scFv 6009F is the first reported recombinant human antibody fragment capable of neutralizing a scorpion venom. These results pave the way for the generation of safer autologous recombinant neutralizing antivenom against scorpion stings. The antibodies of the present invention can be used as part of a composition to treat those in need of treatment including those already stung by one or more scorpions, particularly C. noxius scorpions.