40 results about "Avidity" patented technology

The present disclosure provides methods for reducing sequencing errors comprising one or any combination of: (i) removing deaminated bases in any nucleic acid molecule throughout a library preparation workflow which includes immobilised splints which bind to the library, the use of a compaction oligonucleotide, optionally with an intervening sequence, formation of closed circular nucleic acids, creating gaps using glycosylase and lyase activities at positions with deaminated bases. The library may be sequenced using pairwise sequencing, e.g. with dark sequencing and / or sequencing using a multivalent labelled probe for the formation of an avidity molecule and soluble primer and polymerase. Method for sequencing concatemers in which the concatermers are contacted with polymerases, soluble primers and a multivalent labelled molecule which forms a complex with the polymerase. Detecting polymerase position and nucleobase bound to the polymerase in the complex. These methods generate higher quality base calls during downstream sequencing workflows.

The present invention relates to transthyretin (TTR) fusions useful in the dimerization and tetramerization of antibodies and antibody fragments, such as Fabs. The TTR fusions proteins described herein are particularly useful in increasing antibody avidity and in enhancing antigen clustering. Methods for treating diseases using the fusion proteins of the present invention are described herein.

This application relates to a detection reagent, kit, and method that simultaneously improves sensitivity and broadens the detection range in competitive immunoassay. The reagent includes a detection antibody bound to luminescent microspheres that specifically binds to analyte molecules in the sample, and two sets of labeled antigens containing the same competing antigen and labeled molecules of different molecular weights bound to it. The competing antigen competes with the analyte molecule for binding to the detection antibody, and the affinity of the competing antigen for binding to the detection antibody is higher than that of the analyte molecule for binding to the detection antibody. The technical solution of this application, by using two sets of labeled antigens with different affinities, ensures that the labeled antigens that play a dominant role in samples with varying concentrations of analyte molecules differ. This is suitable for competitive immunoassay of small molecule antigens or haptens in both low-concentration and high-concentration samples, and can broaden the detection range while ensuring high functional sensitivity.

Provided are a BCMA binding protein, a bispecific antibody, a preparation method, and a use. The BCMA binding protein comprises a heavy chain variable region and a light chain variable region. The light chain variable region comprises LCDR1, LCDR2, and LCDR3; and the heavy chain variable region comprises HCDR1, HCDR2, and HCDR3. The BCMA binding protein of the present invention has good specific affinity, binds better to a tumor cell line than a control antibody, and has an internalization effect better than that of the control. The bispecific antibody effectively targets both human BCMA and human CD3.

Provided herein are peptides and conjugates (e.g., radiopharmaceutical conjugates) having avidity for a somatostatin receptor and uses thereof. The conjugate can comprise a 6-mer peptide, such as a monocyclic 6-mer peptide, a metal chelator, and optionally a linker connecting the peptide to the chelator. The radiopharmaceutical conjugate can further comprise a radionuclide bound to the metal chelator. Further provided herein are methods of preparing the conjugates, and methods of treating cancer by administering the described conjugates to a subject in need thereof.

An isolated monoclonal antibody (mAb) or antigen binding fragment thereof having binding specificity for CLDN18 wherein the isolated mAb or antigen binding fragment thereof selectively binds to CLDN18.2 with a measurable affinity and affinity, but not to CLDN18.1.

The invention relates to an antibody affinity detection kit, an antibody affinity detection method and application thereof, the kit comprises a reagent 1, a reagent 2, a discretizing agent and a contrast solution, the reagent 1 comprises luminescent particles coated with antigen, and the luminescent particles internally comprise optical reaction substances; the reagent 2 comprises a biotinylated anti-human IgG antibody; the contrast solution is a matrix solution of the dispersing agent. According to the scheme provided by the invention, the affinity of the IgG antibody in the to-be-detected sample can be conveniently and efficiently detected, the detection efficiency is improved, and the detection result is accurate and reliable.

Developing an effective HIV-1 vaccine is contingent on generating protective antibodies (Abs). Novel antigen delivery methods are needed to enhance immune responses. One promising approach involves directing antigens to dendritic cells (DC) through fused monoclonal antibodies (mAbs) to amplify both cellular and humoral responses. Here, the inventors aimed to refine Langerhans cells (EC) targeting by designing three Env monochains instead of 2 (EC3. Env3) mimicking natural Env conformation. The inventors demonstrated that EC3. Env3 construct (i) elicited a rapid and potent Env-IgG response, (ii) enhanced the avidity of anti-Env IgG that was accompanied by a marked expansion of Tfh and GC B cells and (iii) swiftly induced the formation of structured germinal centers in dLN, indicative of a robust immune response. Finally, significant Tier-1 NeutAb induction was observed in rabbits immunized with the construct. In conclusion, HIV Env antigen can be adaptively targeted to LC as a timer, intensifying both the magnitude and quality of humoral responses. The present invention thus relates to the use of such a construct as LC targeting HIV-1 vaccines.

The dynamics of cell-cell interaction and the formation of a cell bonds involves many interaction partners, a multitude of ligands and receptors including e.g. a specific interaction between e.g. a CAR and a target antigen. This interaction is believed to be highly complex and dependent on many factors such as receptor and antigen density, steric interactions, membrane and receptor mobility, etc. The present inventors delineated from a mathmetical model which best describes the cell-cell interaction and formation of cell-cell bonds. This model most accurately describes the relation between cell fraction bounds and incubation time and allows for highly improving cellular avidity measurements, in particular when performing high throughput measurements, and, provides for a highly useful cellular avidity metric.

Radiopharmaceuticals and conjugates targeting GPC3, as well as their compositions and uses, are provided herein. In one embodiment, a conjugate comprising a peptide having avidity to GPC3 and a metal chelating agent configured to bind to a radionuclide is provided herein. The conjugate described herein may further comprise a linker connecting the chelating agent and the peptide. The conjugate described herein may further comprise a radionuclide. In one embodiment, a radiopharmaceutical comprising a peptide and a metal chelating agent binding to a radionuclide is provided herein. The conjugate described herein may further comprise a linker connecting the chelating agent and the peptide. Methods for treating cancer by administering the radiopharmaceuticals, conjugates, and compositions thereof are further provided herein.

The invention discloses a ferritin nanoprobe for targeting gastric cancer lymphatic metastasis as well as a preparation method and application of the ferritin nanoprobe. According to the present invention, the fusion expression technology and the polycistron expression system are adopted to simultaneously display the two targeting peptide fragments on the cage-shaped surface of the ferritin without affecting the prokaryotic intracellular self-assembly characteristic, such that the method is simple and easy to perform, and the material innovation of the ferritin as the tumor targeting nano-probe is enriched. The three-target ferritin nano-probe constructed by the invention successfully fuses three targets of TfR1, CXCR4 and VEGFR3, endows ferritin with higher and wider affinity in combination with various gastric cancer tumor cells, and remarkably improves the targeting ability of the ferritin nano-probe for various gastric cancer tumor cells or tissues with different surface expression conditions; the difficulty of strong heterogeneity between cells / tissues in gastric cancer lymphatic metastasis diagnosis and treatment is effectively overcome.

Provided herein are, inter alia, antibodies (e.g., humanized antibodies, chimeric antibodies, monoclonal antibodies, biparatopic antibodies, antibody fragments (e.g., Fab')), which bind CD38 with high efficiency and specificity. Inter alia, are provided biparatopic antibodies that bind CD38 specifically and effectively. The biparatopic antibodies provided herein may have an increased binding avidity relative to the monoclonal antibodies they are derived from and are specifically useful for therapeutic and diagnostic purposes.

Multi-specific, optionally multi-valent, antibodies comprising at least one antigen binding moiety in Fv format. Also provided herein are methods for making such multi-specific antibodies and uses thereof for modulating immune responses and treating diseases such as cancer.

This document provides peptides and conjugates (e.g., radiopharmaceutical conjugates) that have avidity for a somatostatin receptor and their uses. The conjugate may comprise a 6-residue peptide, such as a 6-residue monocyclic peptide, a metal chelating agent, and optionally, a linker connecting the peptide to the chelating agent. The radiopharmaceutical conjugate may further comprise a radionuclide attached to the metal chelating agent.This document also provides methods for preparing the conjugates and methods for treating cancer by administering the described conjugates to a subject in need. The radiopharmaceutical conjugate may further comprise a radionuclide bound to the metal chelating agent. This document also provides methods for preparing the conjugates and methods for treating cancer by administering the described conjugates to a subject in need.

Multivalent trident aptamers comprising the general formula [A-SA]2 or 3-L-[SB-B] in which a central branched linker molecule (L) possesses 2 or 3 variable arms ([A-SA]2 or 3), and a root ([SB-B]), connected by a central carbon atom, to provide enhanced affinity and / or avidity with a target are described, as well as methods of making and using the multivalent trident aptamers are provided.

An isolated monoclonal antibody (mAb) or antigen-binding fragment thereof having binding specificity to CLDN18, wherein the isolated mAb or antigen-binding fragment selectively binds to CLDN18.2 with measurable affinity and avidity, but does not bind to CLDN18.1.

The application discloses a non-natural base DNA aptamer targeting Bacillus cereus 5 / B / 6 metal beta-lactamase and a screening method thereof. The screening method uses dNaMTP and dTPT3TP, or dCNMOTP and dTPT3TP as non-natural base nucleoside triphosphate substrates, uses OneTaq DNA polymerase to amplify a DNA library containing non-natural bases, and uses lamda exonuclease to degrade 5' end phosphorylated DNA chains in PCR products, so as to obtain two ssDNA libraries. The non-natural base DNA aptamer targeting Bacillus cereus 5 / B / 6 metal beta-lactamase is screened based on the libraries, and three non-natural base DNA aptamers with a length of 70 nt are obtained. The results of a biological membrane layer interference analysis show that the three non-natural base DNA aptamers have good binding affinity to Bacillus cereus 5 / B / 6 metal beta-lactamase.

The present disclosure provides methods for reducing sequencing errors comprising one or any combination of: (i) removing deaminated bases in any nucleic acid molecule throughout a library preparation workflow which includes immobilised splints which bind to the library, the use of a compaction oligonucleotide, optionally with an intervening sequence, formation of closed circular nucleic acids, creating gaps using glycosylase and lyase activities at positions with deaminated bases. The library may be sequenced using pairwise sequencing, e.g. with dark sequencing and / or sequencing using a multivalent labelled probe for the formation of an avidity molecule and soluble primer and polymerase. Method for sequencing concatemers in which the concatermers are contacted with polymerases, soluble primers and a multivalent labelled molecule which forms a complex with the polymerase. Detecting polymerase position and nucleobase bound to the polymerase in the complex. These methods generate higher quality base calls during downstream sequencing workflows.

Multivalent tetrameric and octameric aptamers comprising a G-quadruplex comprised of monomeric aptamer subunits having the general formula A – SA – [G]n – SB – B in which self-assembly of a G-tetrad linkage structure connects the aptameric arms in parallel orientation to provide enhanced affinity and / or avidity with a target are described, as well as methods of making and using the multivalent aptamers are provided.

The present invention provides radiopharmaceuticals and conjugates targeting GPC3 as well as compositions and uses thereof. In one aspect, provided herein are conjugates comprising a peptide having affinity for GPC3 and a metal chelating agent configured to bind to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. The conjugates described herein may further comprise radionuclides. In one aspect, provided herein is a radiopharmaceutical comprising a peptide and a metal chelating agent that binds to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. Further provided herein are methods of treating cancer by administering the described radiopharmaceuticals, conjugates, compositions thereof.

The current invention relates to cell-cell interaction and in particular to cellular avidity. Provided are improved means and methods to study cell-cell interaction and characterizing cellular avidity. Highly advantageously, it was shown that cellular avidity methods allowed to enrich for B cells expressing an antigen-specific antibody from B cells obtained from subjects exposed to said antigen, e.g. via infection, vaccination, or immunization. Hence, improved means and methods for use in antibody discovery and development are provided. Highly advantageously, it was also shown that cellular avidity methods allowed to determine immune responses against antigens from B cells obtained from subjects exposed to said antigen, e.g. via infection, vaccination, or immunization. Hence, improved means and methods for determining immune response are also provided.

The invention discloses a monoclonal antibody aiming at a new bunyavirus NP protein and application of the monoclonal antibody. The monoclonal antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3. One aspect of the invention provides a pair of paired monoclonal antibodies for detecting the NP protein of the new bunyavirus, one of the paired antibodies is subjected to humanized IgM modification, and the modification can improve the affinity and weaken the HAMA effect. The paired antibody is applied to development of an in-vitro diagnostic kit, and is applied to qualitative detection of the NP protein of the new bunyavirus in blood.

The invention relates to the technical field of biomedical detection, and discloses a multivalent CD301 fusion protein based on an optimized peptide linker, a functionalized magnetic bead and application of the functionalized magnetic bead in CTC capture, the protein is of a single polypeptide chain structure and comprises a plurality of CD301 carbohydrate recognition domains which are connected in series through the peptide linker, and preferably, the protein is in a tetramer form. According to the invention, peptide linkers connecting each recognition domain are specially designed, including optimized flexible linkers or rigid linkers rich in O-glycosylation sites (such as hCG [beta] CTP), so as to regulate the spatial orientation of the domains. By immobilizing the directionally arranged multivalent protein on the surface of the magnetic particle, the binding affinity with a Tn antigen on the surface of a tumor cell is remarkably enhanced by utilizing a multivalent synergistic effect. The method provided by the invention can effectively capture the low EpCAM expression CTC with epithelial-mesenchymal transition (EMT), and has extremely high binding stability under the shear force of blood fluid.

This disclosure provides compositions and methods for a low-avidity, high-affinity and high-specificity biomolecular interaction that is rapidly reversible under physiological conditions. The methods comprise linking biological targets (such as molecules, proteins, DNA, cells, etc.) with polymers and anti-polymer ligands and a way to reverse their binding using physiologically compatible polymeric compounds. The methods also comprise a way to combine different polymer / anti-polymer systems for orthogonal labeling. The compositions comprise labels including particles (fluorescent, magnetic, dense, etc.) conjugated to polymers or labels conjugated to anti-polymer antibodies. The compositions also comprise biomolecules (proteins, antibodies, DNA, etc.) conjugated to the polymers. These methods and compositions represent a major improvement to the state-of-the-art. They are particularly useful for separation and isolation of biological targets using particles, but have important application to other fields including fluorescent imaging.

The present application relates to the field of monoclonal antibody, in particular to the monoclonal antibody against aminoacyl-tRNA synthetase. The present application provides the monoclonal antibody against aminoacyl-tRNA synthetase, the amino acid sequence of the three CDR regions of the heavy chain has the amino acid sequence as shown in SEQ ID NO:1, 2 and 3 respectively; and the amino acid sequence of the three CDR regions of the light chain has the amino acid sequence as shown in SEQ ID NO:4, 5 and 6 respectively. The present application utilizes phage display technology to obtain the aminoacyl-tRNA synthetase monoclonal antibody. The monoclonal antibody has high specificity, high affinity, high detection sensitivity, no matrix effect, solves the interchangeability and consistency of quality control products. Through identification, the monoclonal antibody is used for repeated detection, and has good stability and high accuracy.

An isolated monoclonal antibody (mAb) or antigen-binding fragment thereof having a binding specificity to CLDN18, wherein the isolated mAb or antigen-binding fragment thereof selectively binds to CLDN18.2 with measurable affinity and avidity, but not CLDN18.1.

The present invention provides a recombinant multivalent TREM1 agonist, termed Tetra-CNX, designed to engage and activate TREM1 on myeloid cells. The ligand comprises multiple calnexin luminal domains assembled in a multimeric configuration, enabling high-avidity receptor binding and downstream SYK-dependent signaling. Upon activation, Tetra-CNX enhances lysosomal remodeling and promotes efficient antigen uptake, processing, and presentation via MHC class I and II pathways. This invention enables improved priming of CD4+ and CD8+ T cells and facilitates immune activation in contexts requiring enhanced antigen presentation, including but not limited to cancer, infectious diseases, and vaccine responses. Pharmaceutical compositions and methods of use are provided for modulating myeloid cell function and adaptive immunity through TREM1-targeted intervention.

Provided is a fusion protein platform with improved half-life and relates to a fusion protein platform using an IgG Fc region, IgM region, J chain and / or linker, and relates to a fusion protein produced through the platform, and specifically relates to a fusion protein comprising an IgG Fc region, an IgM region, a J chain, a linker and / or a biologically active molecule. The present disclosure enables to select various biologically active molecules depending on the purpose and use various types of biologically active molecules in combination. The biologically active molecules comprised in the platform can have increased avidity. The fusion protein prepared through the platform has an excellent target recognition and control effect, and there is less risk of unpredictable side effects due to non-specific binding. The half-life in the blood is increased, and thus the treatment effect sought to be achieved through the fusion protein can be maximized.

The invention discloses a novel coronavirus antibody affinity detection kit, a detection method and application. The kit comprises a magnetic particle reagent, a sample treating fluid, a contrast treating fluid and a detection reagent, the magnetic particle reagent comprises coated magnetic particles, the coated magnetic particles are magnetic particles coated with solid-phase antigens, the solid-phase antigens comprise novel coronavirus recombinant spike protein and nucleocapsid protein, and the sample treating fluid is used for detecting the novel coronavirus recombinant spike protein and the nucleocapsid protein. The sample treatment liquid and the control treatment liquid comprise same sample dilution components, the sample treatment liquid further comprises free antigens, the free antigens comprise novel coronavirus recombinant spike proteins and nucleocapsid proteins, and the control treatment liquid does not comprise the novel coronavirus recombinant spike proteins and nucleocapsid proteins. The detection reagent comprises an IgG antibody marked by a chemiluminescent marker. The kit can conveniently and efficiently detect the affinity of the novel coronavirus antibody, and the detection result is accurate and reliable.

Provided herein are radiopharmaceutical conjugate compositions that target EphA2 and uses thereof. In one aspect, provided herein are conjugates comprising a peptide having affinity for EphA2 and a metal chelating agent configured to bind to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. The conjugates described herein may further comprise radionuclides. In another aspect, provided herein are conjugates comprising a peptide having affinity for EphA2 and a covalently bound radionuclide. The conjugates described herein may further comprise a linker linking the radionuclide and the peptide. Further provided herein are methods of treating cancer by administering the conjugates and compositions.