112 results about "Cynomolgus macaque" patented technology

The invention relates to the field of molecular genetics, in particular to a cynomolgus monkey specific SNP site combination, a liquid chip and application of the cynomolgus monkey specific SNP site combination and the liquid chip, 1508 cynomolgus monkey specific SNP sites disclosed and screened by the invention have high polymorphism, and rapid identification, paternity identification and lifelong tracking identification of cynomolgus monkey individuals can be realized. Liquid phase chip design is carried out on the sites, chip inspection is carried out on 383 cynomolgus monkey samples from three different groups, the result shows that the average site detection rate is 99.47%, and it is indicated that the liquid phase chip has excellent site capturing efficiency. According to the method, the genetic detection capability and accuracy of the cynomolgus monkeys can be greatly improved, the genetic detection cost can be remarkably reduced, and an important technical support is provided for improving the breeding management of the cynomolgus monkeys and optimizing the population structure.

The construction of a non-human primate Usher syndrome disease model having USH2A gene mutation, wherein a target sequence against the mRNA of the non-human primate USH2A gene is established and a corresponding sgRNA is synthesized, then a knockout vector is constructed, the sgRNA and a Cas9 mRNA are mixed and injected into a non-human primate embryo to obtain a non-human primate embryo having USH2A gene knockout, and then by means of embryo transfer, a non-human primate having USH2A gene knockout is obtained, which exhibits symptoms of Usher syndrome. Upon detection and identification of the knockout effect, the knockout of the USH2A gene can be effectively realized in a non-human primate cynomolgus monkey embryo and cynomolgus monkeys, which provides a new and effective disease model for the diagnosis and treatment of Usher syndrome in non-human primates.

The application belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting cross binding of human and cynomolgus monkey CD46 and application thereof. The application utilizes alpaca to generate nanoscale antibodies, the molecular weight of which is about 15 kDa, and the nanoscale antibodies can more efficiently penetrate solid tumor tissues or cross blood-brain barrier, and the binding efficiency of the antibodies and target points is as high as possible. The 11 single-domain antibodies prepared by the application have specificity of anti-human and anti-cynomolgus monkey CD46, and in the binding detection with CD46 target proteins and CD46 overexpression cells, the binding efficiency is significantly better than that of Anti-CD46 humanization antibody, and the single-domain antibodies can be used for tumor treatment. Meanwhile, the single-domain antibodies have cross binding ability of cross species, and can be directly used for preclinical pharmacodynamics and safety evaluation, without the need of developing species-specific alternative antibodies, so that the application achieves 'one target and double effect'.

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 (and optionally cynomolgus monkey, mouse, and / or rat B7-H4) and compositions comprising such antibodies or antigen-binding fragments thereof. In a specific aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human B7-H4 increase T cell proliferation, increase interferon-gamma production, and / or deplete B7-H4 expressing cells via ADCC activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4.

The invention belongs to the technical field of biology, and particularly relates to a preparation method of macaca fascicularis liver tissue single-cell suspension. The method comprises the following steps: cleaning macaca fascicularis liver tissues with a pre-cooling buffer solution, and processing into tissue fragments; mixing the tissue fragments with a digestion solution, wherein the digestion solution comprises collagenase I with the final concentration of 1 + / -0.2 mg / ml, collagenase II with the final concentration of 1 + / -0.2 mg / ml, bovine serum albumin with the final concentration of 0.04 + / -0.01% (w / v), DNase I with the final concentration of 10 + / -2 U / ml and the balance of a buffer solution; oscillating and incubating for 30 + / -10min under the conditions of 37 + / -2 DEG C and 150 + / -50rpm, and performing tissue digestion; centrifuging the digested suspension, removing the supernatant, resuspending with a buffer solution, and filtering with a cell sieve to obtain a single-cell primary suspension; and carrying out red blood cell lysis, washing and resuspension on the single-cell primary suspension to prepare the cynomolgus monkey liver tissue single-cell suspension. The method significantly improves the tissue dissociation efficiency, reduces cell adhesion and fragments, effectively protects cell surface antigen epitopes, and has the advantages of simple operation, economy and high efficiency.

This invention relates to anti-CD40 antibodies or antigen-binding fragments thereof that specifically recognize and weakly activate CD40 molecules in humans, cynomolgus monkeys, and mice, as well as immunoconjugates, pharmaceutical compositions, and combination products comprising said anti-CD40 antibodies or antigen-binding fragments thereof. The invention also relates to nucleic acids encoding said anti-CD40 antibodies or antigen-binding fragments thereof and host cells comprising said nucleic acids, and methods for preparing said anti-CD40 antibodies or antigen-binding fragments thereof. Furthermore, the invention relates to the use of said anti-CD40 antibodies or antigen-binding fragments thereof in the prevention or treatment of tumors or infectious diseases in subjects.

The invention belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting cross binding of human and cynomolgus monkey CD46 and application of the single-domain antibody. The alpaca is utilized to generate the nanoscale antibody, the molecular weight of the nanoscale antibody is about 15 kDa, the nanoscale antibody can more efficiently penetrate solid tumor tissues or cross a blood brain barrier, and the binding efficiency of the antibody and a target spot is improved as much as possible. The 11 single-domain antibodies prepared by the invention have the specificity of resisting human and cynomolgus monkey CD46, the binding potency of the 11 single-domain antibodies is remarkably superior to that of an Anti-CD46 humanization antibody in the binding detection of CD46 target protein and CD46 overexpression cells, and the 11 single-domain antibodies can be used for treating tumors. Meanwhile, the single-domain antibody disclosed by the invention has cross-species cross binding capacity, can be directly used for preclinical pharmacodynamics and safety evaluation, does not need to develop a species-specific substitution antibody, and realizes'one target and double effects'.

Provided are antibodies that specifically bind to human urokinase-type plasminogen activator receptor (uPAR). In some cases, the antibodies are cross-reactive with one or more non-human animal uPAR polypeptides, such as non-human primate uPAR, e.g., cynomolgus monkey uPAR. Fusion proteins and conjugates comprising the antibodies of the present disclosure are also provided. Methods of using the antibodies, fusion proteins, and conjugates of the present disclosure to treat conditions associated with uPAR expression and / or activity are also provided. In some embodiments, the condition associated with uPAR expression and / or activity is cancer. Non-limiting examples of such cancers include cancers characterized by cancer cells expressing uPAR on their surface, cancers characterized by stromal cells within the tumor microenvironment expressing uPAR on their surface, and the like.

The invention belongs to the field of immunotoxicology, and particularly relates to a method for immunotyping bone marrow cells by flow cytometry. The flow cytometry immune typing method for bone marrow cells comprises the following steps: collecting macaca fascicularis bone marrow fluid, and preparing the macaca fascicularis bone marrow fluid into single-cell suspension; dyeing the obtained cells by using an antibody combination containing a plurality of fluorescent labels; then, a flow cytometer is used for collecting cell fluorescence signals, a standardized gate setting strategy is executed, and based on collected data, the percentage of each cell subset in CD45 + living white blood cells is calculated to complete immune typing. According to the flow cytometry immune typing method for the bone marrow cells, the problems of low efficiency, low repeatability, low sensitivity and poor specificity of related technologies are solved, and more accurate and reliable data support is provided for early discovery, risk assessment and mechanism research of drug immunotoxicity.

The present invention relates to an isolated antibody or antigen-binding fragment thereof that binds to human A2AP. The isolated antibody or antigen-binding fragment according to the present invention i) cross-reacts with rabbit and / or cynomolgus A2AP, ii) does not inhibit human plasmin activity, and iii) increases plasmin mediated clot lysis in the presence of A2AP.

The invention belongs to the technical field of biological medicine and immunology, and particularly relates to a single-domain antibody targeting PD-L1 cross binding of human and cynomolgus monkeys and application of the single-domain antibody. The single-domain antibody disclosed by the invention has the specificity of resisting PD-L1 of human and cynomolgus monkeys, and shows relatively strong binding efficacy in the binding detection of PD-L1 target protein or PD-L1 overexpression cells; in the detection of blocking PD-1 / PD-L1 functions, a part of the single-domain antibodies even show a blocking effect which is obviously superior to that of Atezolizumab, so that the single-domain antibodies prepared by the invention can be used for diagnosis, treatment and prognosis detection of PD-L1 positive tumors. Meanwhile, the single-domain antibody disclosed by the invention has cross-species cross binding capacity, can be directly used for preclinical pharmacodynamics and safety evaluation, does not need to develop a species-specific substitution antibody, and realizes'one target and double effects'.

The invention provides an antibody or an antigen binding fragment thereof, which is specifically bound with PVRIG and has high binding affinity to human PVRIG protein and cynomolgus monkey PVRIG protein; and the compound has strong activity in the aspects of reporter gene level and CD8T cell activation. Compared with known SRF813 and COM701, the antibody disclosed by the invention comprehensively shows better in-vitro activity, and a part of the antibody is combined with the PD-1 antibody to have an obvious anti-tumor effect, so that the antibody becomes an excellent candidate drug molecule for treatment and diagnosis.

The present invention is directed to selected anti-PD-1 antibodies capable of binding to both cynomolgus monkey PD-1 and to human PD-1: PD-1 mAb 1, PD-1 mAb 2, PD-1 mAb 3, PD-1 mAb 4, PD-1 mAb 5, PD-1 mAb 6, PD-1 mAb 7, PD-1 mAb 8, PD-1 mAb 9, PD-1 mAb 10, PD-1 mAb 11, PD-1 mAb 12, PD-1 mAb 13, PD-1 mAb 14, or PD-1 mAb 15, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to PD-1-binding molecules that comprise PD-1 binding fragments of such anti-PD-1 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such PD-1-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of using molecules that bind PD-1 for stimulating immune responses, as well as methods of detecting PD-1.

The invention belongs to the field of biological medicine, and relates to an anti-IL-31 antibody, and a pharmaceutical composition and application thereof. Specifically, the invention relates to an anti-IL-31 monoclonal antibody or an antigen binding fragment thereof. The antibody has high affinity with human IL-31 and cynomolgus monkey IL-31, can effectively block the combination of IL-31 and its receptor IL-31RA, reduces or eliminates downstream STAT3 phosphorylation signals in cells, significantly inhibits pruritus caused by IL-31, and has good application prospects.

Provided herein are antibodies or antigen-binding portions thereof that bind to STEAP1 and uses thereof. The antibody provided by the invention can be combined with STEAP1 of human, cynomolgus monkeys or mice, and the antibody provided by the invention has good affinity and internalization effect, and has the potential of preparing anti-tumor ADC drugs.

This invention relates to the field of molecular marker screening technology, specifically to a SNP combination and method for paternity testing in cynomolgus monkeys. The method provided by this invention utilizes 100 selected specific SNP combinations (SNP1~SNP100) combined with low-depth sequencing for paternity testing in cynomolgus monkeys. The cost per sample is only 1 / 5 to 1 / 10 of existing high-depth sequencing and 1 / 2 of SNP chips. For large-scale experimental monkey populations (such as populations of thousands), this can save hundreds of thousands of yuan in testing costs annually, significantly reducing the economic burden of breeding and management of experimental monkeys, demonstrating extremely high economic efficiency. The method provided by this invention is applicable to cynomolgus monkey population pedigree management, kinship tracing, breeding pair optimization, and genetic quality control, and can be widely applied in experimental monkey breeding farms, primate research centers, and biomedical research institutions.

The utility model relates to the technical field of machin fixing instruments, in particular to a machin cage inner head fixing tool which comprises a rod body, a pipe sleeve used for connection is integrally constructed on the surface of the bottom end of the rod body, a stud is installed in the pipe sleeve in a screwed mode, and a ring body used for fixing the head of a machin is integrally constructed at the end, away from the pipe sleeve, of the stud. When the cynomolgus monkey is examined and treated, firstly, the cynomolgus monkey cage can be used for fixing the cynomolgus monkey, the rod body is taken through the handle, the ring body at the bottom of the rod body can correspond to the head of the cynomolgus monkey, and the ring body is similar to a circle, so that the contact area with the head of the cynomolgus monkey can be increased, and fixing is firmer; the body and the head of the cynomolgus monkey can be fixed at the same time in cooperation with the animal limiting and fixing function of the animal cage, meanwhile, the stud on the outer side of the ring body is screwed with the pipe sleeve at the bottom of the rod body, the ring body can be conveniently disassembled and assembled, and the ring body of the corresponding specification can be conveniently replaced for use according to the specification of the cynomolgus monkey.

The present invention relates to a fully human anti-CD27L antibody or antibody fragment, comprising a heavy chain variable region and a light chain variable region, wherein the amino acid sequences of the three complementary determining regions of the heavy chain variable region are shown in SEQ ID NOs. 1-3, respectively, and the amino acid sequences of the three complementary determining regions of the light chain variable region are shown in SEQ ID NOs. 5, 7, and 9, respectively; or the amino acid sequences of the three complementary determining regions of the heavy chain variable region are shown in SEQ ID NOs. 1-2 and 4, respectively, and the amino acid sequences of the three complementary determining regions of the light chain variable region are shown in SEQ ID NOs. 6, 8, and 10, respectively. The fully human anti-CD27L antibody or antibody fragment of the present invention can cross-bind to CD27L proteins of humans, cynomolgus monkeys, and mice and has blocking activity against CD27L / CD27, providing new possibilities for further exploration and development of new antibodies targeting CD27L and related clinical research.

Antibodies are provided which bind human and Macaca fascicularis CEACAM5 proteins, as well as isolated nucleic acids, vectors and host cells comprising a sequence encoding the antibodies. Also provided are immunoconjugates comprising the antibodies conjugated or linked to a growth-inhibitory agent, and to pharmaceutical compositions comprising the antibodies, or immunoconjugates. The antibodies or immunoconjugates are used for the treatment of cancer or for diagnostic purposes.

The present invention belongs to the field of biomedicine, and relates to an anti-IL-31 antibody, a pharmaceutical composition thereof and the use thereof. Specifically, the present invention relates to an anti-IL-31 monoclonal antibody or an antigen-binding fragment thereof. The antibody of the present invention has a high affinity for human IL-31 and cynomolgus monkey IL-31, can effectively block the binding of IL-31 to the IL-31RA receptor thereof, can reduce or eliminate intracellular downstream STAT3 phosphorylation signals and significantly inhibit pruritus caused by IL-31, and has good application prospects.

The present disclosure relates to antibodies that bind to human CD94, as well as methods, uses, polynucleotides, vectors, host cells, and pharmaceutical compositions related thereto. In some embodiments, the antibodies are human or humanized antibodies that bind to human CD94 and do not block binding between CD94 and HLA-E. In some embodiments, the antibodies cross-react with cynomolgus CD94. In some embodiments, the antibodies do not promote internalization of surface-expressed CD94 to the extent of existing antibodies. In some embodiments, the antibodies promote ADCC targeting cells that express human CD94, e.g., on the cell surface.

The application provides a non-pH-dependent long-acting anti-serum albumin nanobody and an application thereof. Specifically, the application provides amino acid sequences of VHH chain framework regions FR and complementarity determining regions CDR of the non-pH-dependent long-acting anti-serum albumin nanobody. The application also provides nucleotide sequences encoding the nanobody. The anti-serum albumin nanobody provided by the application can bind to human, mouse, rat and cynomolgus serum albumin under different pH conditions, and can significantly prolong the half-life of a protein drug, thereby providing a research basis for long-acting protein drug development.

The present disclosure relates to an antibody or antigen-binding portion thereof that binds to TSLP protein, and methods of making and using the same. The antibody can bind to human TSLP and / or cynomolgus monkey TSLP with high affinity, can block the binding of TSLP to TSLPR, and can inhibit the transduction of TSLP-stimulated signals through the STAT5 pathway.

The invention provides a method for detecting subtype pSTAT4 and Ki67 signals of peripheral blood T lymphocytes of machin through flow cytometry, and belongs to the technical field of biological detection. According to the method, the integrated analysis of the multi-dimensional functional state of the cynomolgus monkey T lymphocyte is realized, key signal channel activation and proliferation information of different subgroup cells can be synchronously obtained through a single experiment, and the detection comprehensiveness and efficiency are greatly improved. According to the method, an accurate tool capable of directly evaluating the response intensity and proliferation potential of T cells is provided for immune mechanism research based on a machin model, particularly immune therapy or disease research related to regulation and control of pathways such as IL-12 / STAT4 and the like, and the data dimension and reliability of preclinical immunological evaluation are remarkably enhanced.

The application discloses a CD3 antibody and application thereof, and relates to the technical field of biological medicine.The antibody provided by the application is a full human antibody, which fundamentally reduces immunogenicity risk, and lays a material foundation for developing safer T cell redirection therapy.The antibody has cross-reactivity with cynomolgus monkey CD3, can be directly used for a cynomolgus monkey model to perform systematic pharmacodynamics, pharmacokinetics and safety evaluation, greatly improves the prediction value of preclinical data, and accelerates the conversion process of a candidate molecule to clinical research.

The invention belongs to the technical field of molecular genetics and biology, and particularly relates to a cynomolgus monkey specific SNP site combination, a liquid chip and application of the cynomolgus monkey specific SNP site combination in individual recognition and paternity identification. The invention provides a combination of 1508 specific SNP (Single Nucleotide Polymorphism) sites of cynomolgus monkeys with high polymorphism. By utilizing the site combination, the invention further develops a high-throughput liquid phase chip which is suitable for efficient genetic analysis of cynomolgus monkeys. Experiments prove that when the liquid chip is used for detecting 383 cynomolgus monkey samples from three different groups, the average site detection rate reaches 99.47%, the recorded parent-child relationship can be accurately restored, and it is proved that the site combination and the liquid chip have extremely high accuracy and reliability in paternity identification. According to the technical scheme provided by the invention, the genetic detection efficiency and identification accuracy of the cynomolgus monkeys can be remarkably improved, and a powerful technical tool is provided for scientific breeding management, population genetic structure optimization and genetic resource protection of the cynomolgus monkeys.

The invention provides a small nucleic acid drug in-vitro screening method, and belongs to the technical field of biological detection. Aiming at the problem that small nucleic acid drugs are difficult to screen quickly in the prior art, primary hepatocytes of cynomolgus monkeys are used as a screening basic model, to-be-detected small nucleic acid drugs are transfected, ACTB, ASGR1 and ASGR2 are used as target genes, cell lysates are collected at different time points to extract mRNA, and the mRNA is subjected to qPCR amplification reaction, so that the small nucleic acid drugs are screened quickly. And evaluating the regulation effect of the drug on the target gene according to the amplification product amount so as to screen the drug. The method can quickly and accurately screen small nucleic acid drugs, and provides powerful support for drug research and development.

The present disclosure relates to the development and application of a novel tumor adapter therapeutic drug. The therapeutic drug comprises a bispecific antibody binding to GPC3 and CD3, which comprises a first binding domain binding to GPC3 on the surface of target cells and a second binding domain binding to CD3 on the surface of T cells. The bispecific antibody can effectively inhibit the growth of transplanted tumors in immune-reconstituted mice at an extremely low dose, i.e. can inhibit tumor growth; the toxicology study in cynomolgus monkeys also shows that the animals are well tolerated to the bispecific antibody, and the bispecific antibody is superior to the same antibody in terms of efficacy and safety.

The invention provides a method for detecting a double-target agonist drug neutralizing antibody in cynomolgus monkey serum, and belongs to the technical field of biological detection. The invention establishes and verifies a stable, reliable and efficient detection method which can sensitively and specifically detect the neutralizing antibody activity of the cynomolgus monkey serum to the double-target agonist drug. The method has good precision, accuracy and reproducibility, effectively overcomes the interference of complex components in a serum sample, and ensures the accuracy and reliability of a detection result. The successful application of the method can provide key technical support for immunogenicity evaluation of double-target agonist drugs before clinical application and in clinical research, and the method has important practical significance for guaranteeing smooth drug research and development and medication safety.

Lassa fever is a zoonotic viral hemorrhagic disease caused by Lassa virus (LASV), endemic in multiple west African countries where the multimammate rat is a main virus reservoir. The broad geographic range of the rodent host places a large population at risk of serious illness. LASV is also a bioterrorism threat. A LASV vaccine is an unmet need. Applicants advance a vaccine based on a live vesicular stomatitis virus vector for immunizing against the LASV surface glycoprotein. Preclinical evaluation exhibited high efficacy in cynomolgus macaques. The animals developed serum antibodies that could mediate antiviral effector functions including direct neutralization of virus infectivity. This vaccine candidate elicited robust protective immunity in cynomolgus macaques that prevented development of detectable viremia and disease for at least 1 year after vaccination. These protective immune response features provide valuable data for comparison to an ongoing phase 1 clinical trial and planned phase 2b / 3 clinical trials.