33 results about "Affinity maturation" patented technology

The invention relates to the technical field of biology, in particular to a method for improving affinity of a nano antibody based on computer-aided design. According to the method, a series of bioinformatics tools for nano antibody affinity maturation are investigated and researched in literatures, and part of databases, servers and software are optimized to construct a set of computer-aided design (CAD) nano antibody affinity improvement method by evaluating the operability and the improvement effect of the tools. In order to verify the effectiveness and universality of the method, based on the method, a high-affinity mutant nano antibody is virtually screened out of an Anti-Nectin-4 camel source nano antibody NBNT-1 and an Anti-PD-L1 shark source nano antibody NBNT4 screened in a synthetic library through model construction, model evaluation, site prediction, molecular docking, structural analysis, mutation prediction and mutation evaluation. Traditional in-vitro affinity maturation methods, such as error-prone PCR, are low in screening efficiency, large in randomness introduced by mutation, long in experimental period, large in workload and difficult to accurately optimize the affinity of target molecules. According to the method, various defects of a traditional in-vitro affinity maturation method are overcome, and the success rate and efficiency of affinity maturation are improved.

The application discloses an anti-human PD1 full human antibody and application thereof, and relates to the field of antibodies, and specifically discloses an anti-human PD1 full human antibody, which comprises three heavy chain variable regions HCDR and three light chain variable regions LCDR; the three heavy chain variable regions comprise: HCDR1 is an amino acid sequence as shown in SEQ ID NO. 4, HCDR2 is an amino acid sequence as shown in SEQ ID NO. 5, and HCDR3 is an amino acid sequence as shown in SEQ ID NO. 6; and the three light chain variable regions comprise: LCDR1 is an amino acid sequence as shown in SEQ ID NO. 1, LCDR2 is an amino acid sequence as shown in SEQ ID NO. 2, and LCDR3 is an amino acid sequence as shown in SEQ ID NO. 3. The application has reduced immunogenicity, and affinity maturation and activity are greatly improved.

The present invention provides anti-CD155 antibodies and their applications, and provides anti-CD155 chimeric antibodies, humanized antibodies, and affinity-matured humanized antibodies, which specifically target and bind to the CD155 receptor, inhibit the binding of CD155 to its receptors TIGIT, CD96, and CD226, and have the characteristic of not inducing apoptosis of CD155 cells.

This invention discloses an APLN monoclonal antibody, its preparation method, and its applications. The APLN monoclonal antibody includes a light chain variable region and a heavy chain variable region. The amino acid sequence of the light chain variable region is shown in SEQ ID No:1, and the amino acid sequence of the heavy chain variable region is shown in SEQ ID No:2. The APLN monoclonal antibody is obtained by immunizing mice with APLN protein, followed by single-cell B-cell sorting and single-cell PCR. Utilizing advanced single-cell B-cell cloning technology combined with single-cell PCR, a novel APLN monoclonal antibody has been developed. The obtained antibody sequence is the result of natural affinity maturation screening by the in vivo immune system, requiring no additional humanization or in vitro affinity maturation steps. It retains the natural high affinity and specificity, and can directly obtain all-natural antibodies with high affinity and high specificity.

Provided herein are affinity matured anti-galectin-9 (Gal9) antibodies. The antibodies have improved binding affinity to Gal9. Also provided herein are method of use of the affinity matured anti-Gal9 antibodies, including methods of treatment of cancer, methods of rescuing or promoting effector T cell proliferation, methods of enhancing effector T cell activity, and / or of identifying and treating cancer in a subject including the administration of the anti-Gal9 antibodies described herein. Also provided are polynucleotides encoding the heavy chain or the light chain or the antigen-binding portion thereof described herein, and vectors, especially expression vectors, including the polynucleotides described herein.

OF THE INVENTION Provided herein is a humanized J3 derivative antigen binding molecule and uses thereof.

Provided are affinity matured and humanized antibodies and antigen-binding fragments thereof that specifically bind to human neuropilin-2 (NRP2) polypeptides, including those that modulate binding interactions between human NRP2 and at least one NRP2 ligand, and which thereby modulate subsequent NRP2-mediated downstream signaling events, including related therapeutic compositions and methods for modulating NRP2 activity and treating diseases such as NRP2-associated diseases.

The present application relates to a binding molecule capable of specifically binding to Lrig-1 protein, which is a protein expressed on the surface of regulatory T cells. The binding molecule provided by the present application can inhibit the function of regulatory T cells, thereby effectively preventing, improving or treating cancer, especially solid tumors. In addition, compared with commercially available antibodies against Lrig-1, the binding molecule provided by the present application can more effectively target Lrig-1 protein and show excellent binding affinity.

The application discloses a novel coronavirus neutralizing antibody, a detection kit and application thereof, an amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No. 1, and an amino acid sequence of a light chain variable region is shown as SEQ ID No. 2. The application screens the affinity-matured antibody through bioinformatics analysis of a single B cell, combines single-cell RNA sequencing, VDJ rearrangement analysis and somatic hypermutation research, optimizes the antibody screening process, avoids blindness of a traditional method, and improves the accuracy and effectiveness of antibody screening. The neutralizing antibody GR58 provided by the application can specifically combine with a RBD domain of SARS-CoV-2 and a S-Trimer domain of an Omicron mutant strain through the heavy chain and light chain variable regions, realizes broad-spectrum neutralization of SARS-CoV-2 and mutant strains thereof, and the antibody GR58 is significantly superior to other antibodies in the binding activity of S-Trimer and RBD under 2-fold and 300-fold dilution conditions, indicating that the antibody has high affinity and dilution stability, and is suitable for clinical large-dose administration requirements.

Using rabbit antibody technology, an anti-TfR1 monoclonal antibody having high affinity, high specificity and high blood safety is obtained by means of phage immune library construction and screening, and the anti-TfR1 monoclonal antibody is subjected to humanization and affinity maturation treatment to obtain a humanized anti-TfR1 monoclonal antibody having high affinity without inducing immunogenicity.

Provided in the present invention is a T cell receptor engineering modification method, which comprises the steps of: obtaining CDR regions of a given T cell receptor sequence by means of a database, mutating one or more amino acid residues in the CDR regions into histidine, and establishing a first T cell receptor mutation library. The T cell receptor engineering modification method provided by the present invention is based on a histidine scanning method, realizes TCR engineering modification independent of three-dimensional structures, overcomes the disadvantages of high affinity and realizes the modification of TCRs with low affinity and high activation, thereby providing more options for clinical use. The T cell receptor provided by the present invention comprises the following six CDR regions, CDR1α, CDR2α and CDR3α in a TCRα chain, and CDR1β, CDR2β and CDR3β in a TCRβ chain, the amino acid sequences of which are shown as SEQ ID No. 1-6, respectively. In the present invention, engineering modification of a wild-type MAGE-A3 TCR molecule is achieved by means of a catch bond to obtain an efficient and non-toxic TCR targeting MAGE-A3, which is free of toxic and side effects caused by affinity maturation. Moreover, the engineered TCR is applied to TCR-T cell preparation for solid tumor treatment.

Provided are affinity-matured single-domain anti-PD-L1 antibodies and polypeptides (e.g., multispecific antibodies and chimeric antigen receptors) comprising the single-domain antibodies. The antibodies, including their humanized counterparts, exhibit excellent activity and are suitable for use in a variety of multispecific antibody formats. Also provided are methods of using the antibodies or polypeptides to treat and diagnose diseases such as cancer and infectious diseases. The present disclosure provides novel single-domain antibodies and affinity-matured counterparts that target the human PD-L1 protein.

To provide anti-FcRH5 antibodies (e.g. bispecific antibodies, e.g. FcRH5 T cell-dependent bispecific antibodies) for the treatment of cell proliferative disorders (e.g. cancers, e.g. FcRH5-positive cancers, e.g., multiple myeloma), compositions, and methods of using them.SOLUTION: The present invention relates to anti-FcRH5 antibodies, including anti-FcRH5 antibodies (e.g. FcRH5 T cell-dependent bispecific (TDB) antibodies) that comprise an FcRH5 binding domain including a specific amino acid sequence, and a CD3 binding domain including another specific amino acid sequence, and methods of using the same.SELECTED DRAWING: None

The application discloses a novel coronavirus neutralizing antibody GR46, a detection kit and application thereof, an amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No. 1, and an amino acid sequence of a light chain variable region is shown as SEQ ID No. 2. The application screens the affinity-matured antibody through bioinformatics analysis of a single B cell, combines single-cell RNA sequencing, VDJ rearrangement analysis and somatic hypermutation research, optimizes the antibody screening process, avoids blindness of a traditional method, and improves the accuracy and effectiveness of antibody screening. The neutralizing antibody GR46 provided by the application can specifically combine with a RBD domain of SARS-CoV-2 and a S-Trimer domain of an Omicron mutant strain through the heavy chain and light chain variable regions, realizes broad-spectrum neutralization of SARS-CoV-2 and mutant strains thereof, and the antibody GR46 is significantly superior to other antibodies in the binding activity of S-Trimer and RBD under 2-fold and 300-fold dilution conditions, indicating that the antibody GR46 has high affinity and dilution stability, and is suitable for clinical large-dose administration requirements.

Provided herein are recombinant antibodies and antigen-binding fragments thereof useful for binding to and inhibiting carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Also provided are methods of using the disclosed CEACAM1 antibodies and antigen-binding fragments thereof for reducing T-cell tolerance and for the treatment of cancer and infection.

Provided are affinity-maturated single domain anti-PD-L1 antibodies and polypeptides, such as multispecific antibodies and chimeric antigen receptors, that include these single domain antibodies. These antibodies, including their humanized counterparts, exhibited superior activities and are suitable for use in various multispecific antibody formats. Methods of using the antibodies or polypeptides for treating and diagnosing diseases such as cancer and infectious diseases are also provided.

The application discloses a nanobody Nb3-P-3 capable of specifically recognizing fludioxonil and an application thereof. An amino acid sequence of the nanobody Nb3-P-3 is shown as SEQ ID No. 1. An AI-guided affinity maturation strategy is adopted to perform multi-point synergistic mutation and computer-aided screening on a key binding site of an initial nanobody Nb3, so as to obtain the nanobody Nb3-P-3. The nanobody can specifically recognize fludioxonil, a half-inhibitory concentration (IC 50 ) of the nanobody for fludioxonil is 1.95 ng / mL, a lowest detection limit (LOD) is 0.09 ng / mL, a linear range (IC 20 -IC 80 ) is 0.29-19.30 ng / mL, and the nanobody has excellent organic solvent resistance. The nanobody Nb3-P-3 has an excellent application prospect in rapid detection of fludioxonil residues.

The invention discloses an anti-transferrin receptor (TfR1) antibody or an antigen binding fragment thereof. The preparation method comprises the following steps: carrying out phage immunization library-building screening by using a rabbit anti-technology to obtain an anti-TfR1 monoclonal antibody with high affinity, high specificity and high blood safety, and carrying out humanization and affinity maturation treatment on the anti-TfR1 monoclonal antibody to obtain the humanized anti-TfR1 monoclonal antibody which has high affinity and does not cause immunogenicity.

This invention relates to the field of biomedicine, and in particular to a T-cell receptor targeting MAGE-A3 and its applications. The T-cell receptor provided by this invention comprises six CDR regions: CDR1α, CDR2α, and CDR3α in the TCRα chain, and CDR1β, CDR2β, and CDR3β in the TCRβ chain, with amino acid sequences shown in SEQ ID Nos. 1-6, respectively. This invention utilizes reverse-locking engineering to modify wild-type MAGE-A3 TCR molecules, obtaining a highly efficient and non-toxic TCR targeting MAGE-A3, avoiding the toxic side effects caused by affinity maturation. This engineered TCR is then applied to the preparation of TCR-T cells for the treatment of solid tumors.

The application discloses a novel coronavirus neutralizing antibody, a detection kit and application thereof, an amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No. 1, and an amino acid sequence of a light chain variable region is shown as SEQ ID No. 2. The application screens the affinity-matured antibody through bioinformatics analysis of a single B cell, combines single-cell RNA sequencing, VDJ rearrangement analysis and somatic hypermutation research, optimizes the antibody screening process, avoids blindness of a traditional method, and improves the accuracy and effectiveness of antibody screening. The neutralizing antibody GR75 provided by the application can specifically combine with a RBD domain of SARS-CoV-2 and a S-Trimer domain of an Omicron mutant strain through the heavy chain and light chain variable regions, realizes broad-spectrum neutralization of SARS-CoV-2 and mutant strains thereof, and the antibody GR75 is significantly superior to other antibodies in the binding activity of S-Trimer and RBD under 2-fold and 300-fold dilution conditions, indicating that the antibody has high affinity and dilution stability, and is suitable for clinical large-dose administration requirements.

The present disclosure provides antibodies that specifically bind to human FAM19A5 and compositions comprising such antibodies. In some embodiments, antibodies are de-immunized to reduce immunogenicity in a human subject. In certain embodiments, antibodies have undergone affinity maturation. In some embodiments, the anti-FAM19A5 antibodies can modulate FAM19A5 activity, e.g., inhibit, suppress, reduce, or reverse the onset of reactive gliosis and / or excessive proliferation of reactive astrocytes, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as central nervous system damage, a degenerative brain disorder, a neuropathic pain, or a cancer, by administering an antibody that specifically binds to human FAM19A5.

The present invention provides affinity matured recombinant monoclonal antibodies (mAbs) and fragments that bind specifically to an HLA-E- peptide complex, including HLA-E-VL9 complexes, and regulate the cytotoxicity effector cell function of NK. Herein, monoclonal antibodies were recombinantly derived from isolated functional HLA-E-VL9-specific mAbs from the naïve human B cell repertoire. Such antibodies are capable of regulating effector cell cytotoxicity and can preferentially recognize HLA-E-VL9 peptide complexes expressed on the surface of tumor cells. The monoclonal antibodies were subject to one or more rounds of affinity maturation. The invention provides methods for using affinity matured HLA-E-VL9 mAbs to modulate NK cell function as part of immunotherapeutic strategies.

The present disclosure provides antibodies that specifically bind to human FAM19A5 and compositions comprising such antibodies. In some embodiments, antibodies are de-immunized to reduce immunogenicity in a human subject. In certain embodiments, antibodies have undergone affinity maturation. In some embodiments, the anti-FAM19A5 antibodies can modulate FAM19A5 activity, e.g, inhibit, suppress, reduce, or reverse the onset of reactive gliosis and / or excessive proliferation of reactive astrocytes, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as central nervous system damage, a degenerative brain disorder, a neuropathic pain, or a cancer, by administering an antibody that specifically binds to human FAM19A5.

The application discloses a novel coronavirus neutralizing antibody, a detection kit and application thereof, an amino acid sequence of a heavy chain variable region of the neutralizing antibody is shown as SEQ ID No. 1, and an amino acid sequence of a light chain variable region is shown as SEQ ID No. 2. The application screens the affinity-matured antibody through bioinformatics analysis of a single B cell, combines single-cell RNA sequencing, VDJ rearrangement analysis and somatic hypermutation research, optimizes the antibody screening process, avoids blindness of a traditional method, and improves the accuracy and effectiveness of antibody screening. The neutralizing antibody GR12 provided by the application can specifically combine with a RBD domain of SARS-CoV-2 and a S-Trimer domain of an Omicron mutant strain through the heavy chain and light chain variable regions, realizes broad-spectrum neutralization of SARS-CoV-2 and mutant strains thereof, and the antibody GR12 is significantly superior to other antibodies in the binding activity of S-Trimer and RBD under 2-fold and 300-fold dilution conditions, indicating that the antibody has high affinity and dilution stability, and is suitable for clinical large-dose administration requirements.

This disclosure relates to methods of generating antibody libraries, antibody libraries produced using such methods, and variant antibodies. Presently, methods of improving antibody binding (affinity maturation assays) require the screening of vast libraries of antibody variants (often >1010) to identify a small fraction of variants with improved characteristics. The present invention involves taking the nucleotide sequence of the framework and complementarity determining region of a target antibody and identifying motifs which would be recognised by deamination somatic hypermutation enzymes. A small library of variants is then created which incorporate one or more of these mutations. It was found that a relatively high proportion of the variants have an increased affinity. The technique of the present invention was demonstrated on the trastuzumab and Cathepsin S antibodies, and the variants produced are also claimed.

The disclosure provides methods for promoting affinity maturation, and in particular in vivo affinity maturation, of antibodies. The disclosure also provides a system of affinity maturation of an antibody as well as compositions comprising antibodies generated from methods described herein and polynucleotides encoding such systems.

To provide affinity matured MICA antibodies and applications thereof, more specifically, antibodies or antigen binding fragments thereof, nucleic acid molecules, expression vectors, methods for preparing the antibodies or antigen binding fragments thereof, recombinant cells, compositions and uses thereof, pharmaceuticals and uses thereof.SOLUTION: The invention presents an antibody or antigen binding fragment thereof and uses thereof. The antibody or antigen binding fragment thereof comprises heavy chain variable region CDR1, CDR2 and CDR3 each having a specific amino acid sequence or an amino acid sequence having at least 80% identity to the specific sequence, and light chain variable region CDR1, CDR2 and CDR3 each having a specific amino acid sequence or an amino acid sequence having at least 80% identity to the specific sequence. The antibody or antigen binding fragment thereof binds to human and monkey MICA protein with high affinity and promotes the tumor killing by PBMC (human peripheral blood mononuclear cell).SELECTED DRAWING: Figure 1

The application belongs to the technical field of biological medicine, and specifically discloses a single-domain antibody against human MMP-1, a mesenchymal stem cell exosome targeted and modified by the single-domain antibody, and application of the single-domain antibody and the exosome in repairing skin photoaging. The surface of the exosome is covalently connected with the single-domain antibody that specifically targets human MMP-1 through click chemistry technology, the single-domain antibody has an amino acid sequence as shown in SEQ ID NO:1, and is obtained through camel phage display library screening and affinity maturation, and has a high affinity of a nanomolar level to MMP-1. The preparation method comprises screening and expression of the single-domain antibody, extraction and purification of the mesenchymal stem cell exosome, and directional coupling through DBCO-azide click chemistry. The modified exosome can specifically recognize and enrich in photoaged skin tissue, significantly inhibit collagen degradation, promote extracellular matrix reconstruction, relieve oxidative stress and inflammatory response, and exhibits excellent effects in repairing skin photoaging caused by ultraviolet rays, and is suitable for development of skin repair drugs and cosmetics.

Disclosed are compositions and methods for targeted treatment of TAG-72-expressing cancers. In particular, affinity maturated single chain variable fragment (scFv) antibodies that bind TAG-72 on cancer cells are disclosed.