79 results about "Cynomolgus macaque" patented technology

Isolated antibodies that bind to human CD38 and cynomolgus CD38 are disclosed. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies, and therapeutic and diagnostic methods for using the disclosed antibodies.

CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey) are presented. Uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and / or inflammatory diseases and other conditions are presented.

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAGS as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

The invention belongs to a construction method of an animal model, and in particular relates to a construction method of a cynomolgus macaque model for alcoholic liver disease. The construction method of the cynomolgus macaque model for alcoholic liver disease comprises the following steps: screening experimental animals, feeding the screened experimental animals with high-glucose and high-fat feed, and conducting liver biopsy and acquisition of the determined model. The construction method of the cynomolgus macaque model for alcoholic liver disease provided by the invention is short in duration and high in success rate; the construction method is suitable for researching the occurrence mechanism of the alcoholic liver disease and is convenient for screening drugs for treating the alcoholic liver disease and for evaluating the efficacy of the drugs on the alcoholic liver disease; and the construction method has a good application prospect.

The invention provides a diabetes primate model construction method. The method comprises the following steps of injecting streptozotocin into cynomolgus monkeys according to a small-dose progressiveincrease method, feeding the cynomolgus monkeys with high-sugar and high-fat feed at the same time, and after injecting the streptozotocin into the cynomolgus monkeys and feeding the cynomolgus monkeys with the high-sugar and high-fat feed for a period of time, increasing night illumination to induce the cynomolgus monkeys to become diabetes models. The diabetic monkey model is successfully established by adopting the method for 1.5-6 months, the model has the core characteristics of insulin resistance and hyperglycemia, the duration of hyperglycemia is long, and the hyperglycemia is not reduced after more than 200 days. The animal model established by the invention can be used in animal experiments with longer duration, and can be sold as a mature animal model to generate economic benefits.

The present invention includes antibodies and antigen-binding fragments thereof that specifically bind to human or cynomolgous monkey LAG3 as well as immunoglobulin chains thereof and polynucleotides encoding the same along with injection devices comprising such antibodies or fragments. Vaccines including such antibodies and fragments as well as compositions comprising the antibodies and fragments (e.g., including anti-PD1 antibodies) are included in the invention. Methods for treating or preventing cancer or infection using such compositions are also provided. In addition, methods for recombinant expression of the antibodies and fragments are part of the present invention.

The invention discloses an antibody targeting BCMA, a bispecific antibody targeting BCMA and CD3, and applications of the antibody and the bispecific antibody. The antibody targeting the BCMA comprises two heavy chain variable regions, wherein the heavy chain variable regions comprise HCDR1, HCDR2 and HCDR3 which are respectively shown as amino acid sequences of SEQ ID NO: 22, SEQ ID NO: 33 and SEQ ID NO: 42, or HCDR1, HCDR2 and HCDR3 shown as amino acid sequences of SEQ ID NO: 26, SEQ ID NO: 37 and SEQ ID NO: 41 respectively. The antibody provided by the invention effectively targets human BCMA and is combined with cynomolgus monkey BCMA; and the bispecific antibody effectively targets human BCMA and human CD3 at the same time, and can be combined with cynomolgus monkey BCMA and cynomolgus monkey CD3.

The invention aims at improving cynomolgus magnetic resonance scanning methods and consequently providing legible brain magnetic resonance images. The invention provides a cynomolgus magnetic resonance scanning method that utilizes a Philips Intera A chiva 3.0T magnetic resonance machine for scanning, a T1 scanning sequence is IR with the visual field of 120mm, the TR / TE of 2153ms / 13ms, the seam thickness / interval of 3mm / 0.3mm and the matrix of 256 multiplied by 256, while a T2 weighted image scanning sequence is SE with the visual field of 12cm multiplied by 12cm, the TR / TE of 3200ms / 102ms, the seam thickness / interval of 3mm / 0.3mm and the matrix of 256 multiplied by 256. The cynomolgus magnetic resonance scanning method can provide legible brain magnetic resonance images, and has greater significance in the displaying of cynomolgus craniocerebral anatomical structure and cytological marking and magnetic resonance tracing after brain transplantation.

The invention discloses development and an application of a therapeutic agent for TSLP-related diseases, and relates to an antibody binding to TSLP protein or an antigen binding part thereof as well as a preparation method and an application of the antibody. The antibody can be combined with human TSLP and / or cynomolgus monkey TSLP with high affinity, can block the combination of the TSLP and TSLPR, and can inhibit the transduction of a TSLP stimulating signal through an STAT5 pathway.

The invention discloses a method for freezing the semen of a Macaca fascicularis. In the method, fresh semen activity of a semen sample is required to be more than or equal to 0.7. The freezing method comprises the following operating steps of: 1) freezing diluent prescription and diluent preparation for the semen of the Macaca fascicularis; 2) semen dilution; 3) semen package; 4) semen balance; 5) semen freezing; and 6) frozen semen unfreezing. The method has the following advantages that: by using the technology of the invention, in the processes of freezing and unfreezing the semen of the Macaca fascicularis, the motility rate and the recovery rate of the semen after freezing and unfreezing respectively reach 45 percent and 62 percent, so that the reproductive efficiency of good male Macaca fascicularis can be brought into full play, genetic gene of good Macaca fascicularis can be conserved, and referential experience is provided for the research on semen cryopreservation of other rare or endangered primates at the same time.

The invention discloses a method for establishing a Macaca fascicularis experimental autoimmune encephalomyelitis model and application thereof. According to a concrete technical scheme in the invention, the method comprises the following steps: preparing an emulsion (an MOG solution: CFA = 1: 1) from MOG 34-56 (100 mu g / ml); narcotizing Macaca fascicularis for experiments and injecting 1 ml of the prepared emulsion at 10 injection points; carrying out immunization injection of the emulsion (secondary immunization) according to the above-mentioned method and dose in 7 days after the primary immunization injection (primary immunization); carrying out clinical observation in one day after primary immunization and recording clinical scores; and determining pathogenic sites, degrees and the like by using an MRI iconographic method at pathogenic time nodes. The model established in the invention has an application value which cannot be achieved by other rodent models, has the characteristics of recurrence-alleviation type attacks, low cost, wide availability of Macaca fascicularis for experiments and the like compared with a Macaca rhesus model and has a wide application scope in fields related to multiple sclerosis diseases.

The invention relates to a PCR (Polymerase Chain Reaction) primer group, a fluorescence quantitative PCR detection chip and a detection method for analyzing the associated gene expression state of T2DM (Type 2 Diabetes Mellitus) for human and Cynomolgus monkeys simultaneously. The T2DM detection primer group for human and monkeys comprises amplification primer pairs respectively for amplifying T2DM disease associated protein genes as follows: ACE, ACLY, G6PD, GSK3B, HMOX1, IDE, PRKCB1, PYGL, AQP, CCR2B, CEACAM1, CTLA4, GCGR, ICAM1, NSF, RAB4A, SELL, SNAP23B, STX4, STXBP2, TNFRSF1A, VAMP3, VAPA, IFNG, INS, TGFB1, TNFA, IGFBP5, INPPL1, PIK3C2B, PIK3R1, IKBA, NEUROD1, NFKB1, PPARGC1A and AGT, and the sequences of the gene amplification primer pairs are nucleotide sequences respectively shown as SEQ ID NO: 1-72. The invention also provides the fluorescence quantitative PCR detection chip and the detection method comprising the PCR primer group. The invention has the beneficial effects of performing accurate quantification and detection on T2DM disease associated genes for human and monkeys simultaneously, thus having far reaching importance for promoting fundamental research, preventive detection and clinical treatment of diabetes.

A CD47 single-domain antibody and use thereof, and in particularly, a blocking type single-domain antibody for integrin-related protein (CD47) and derivative proteins thereof. In particular, disclosed are an integrin-related protein (CD47) binding molecule and use thereof, particularly in the treatment and / or prevention, or diagnosis of CD47-associated diseases, such as tumors. The CD47 single-domain antibody involved can effectively block the interaction between CD47 and a ligand SIRPa thereof, has good binding activity, blocking activity, affinity and stability, can effectively enhance the phagocytosis of tumor cells by macrophages, and shows significant anti-tumor activity in both a human lymphoma model and a human ovarian cancer model. In addition, the antibody does not cause hemoagglutination in vitro, and shows excellent safety in cynomolgus monkeys.

The invention discloses a method for detecting the concentration of FGF21 in cynomolgus monkey serum. The method comprises the following steps: (1) adding a to-be-detected serum sample on a 96 microwell plate pre-coated with rabbit anti-human FGF21 polyclonal antibody, and incubating; (2) washing the plate, adding a detection antibody, and incubating; (3) washing the plate, adding an enzyme-labeled antibody, and incubating; (4) after washing the plate, adding an HRP substrate tetramethyl benzidine, carrying out dark incubation, then adding a stop solution to stop the enzyme reaction, and determining the absorbance at 450 nm; and (5) calculating according to the absorbance value to obtain the FGF21 concentration in the serum. The detection method has high accuracy and precision, is slightlyinterfered, and can be used for better researching the action mechanism of the fibroblast growth factor 21.

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for human and Macaca fascicularis CEACAM6 (Carcinoembryonic antigen-related cell adhesion molecule 6, CD66c, Non-specific crossreacting antigen, NCA, NCA-50 / 90), and which do not significantly cross-react with the closely related human CEACAM1, human CEACAM3, and human CEACAM5. The invention further provides methods to generate this kind of antibodies. The antibodies, accordingly, can be used to treat cancer and other disorders and conditions associated with expression of the CEACAM6. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use.

The invention discloses an SNP mark for evaluating a genetic background infiltration phenomenon of rhesus monkeys in cynomolgus monkeys and application of the SNP mark. The SNP mark comprises 48 SNP loci, namely SNP1-SNP48 which are respectively located at loci 151 in nucleotide sequences represented by SEQ ID NO:1-SEQ ID:NO48. By utilizing advantages of biological information techniques, the SNP mark for evaluating the genetic background infiltration phenomenon of the rhesus monkeys in the cynomolgus monkeys is developed and is applied to the evaluation of a genetic background infiltration level of the rhesus monkeys in the cynomolgus monkeys, so that the cost is greatly lowered, and the operation is simplified. By applying the SNP mark, rapid preliminary screening can be realized, the detection cost is lowered, and therefore, the standardized process of the evaluation of the genetic background infiltration phenomenon of the rhesus monkeys in the cynomolgus monkeys is promoted.

The invention discloses cynomolgus monkey P450 2C18 drug metabolizing enzyme and a co-expression recombinant vector of the cynomolgus monkey P450 2C18 drug metabolizing enzyme and cynomolgus monkey P450 oxidoreductase. The cynomolgus monkey P450 2C18 drug metabolizing enzyme can catalyze hydroxylation of piroxicam and a gene sequence of the cynomolgus monkey P450 2C18 drug metabolizing enzyme or a complementary sequence of the cynomolgus monkey P450 2C18 drug metabolizing enzyme is a sequence in SEQ ID NO:1 with the mutation rate of 0-1%. The co-expression recombinant vector of the cynomolgus monkey P450 2C18 drug metabolizing enzyme and the cynomolgus monkey P450 oxidoreductase comprises an open reading frame of the sequence of the cynomolgus monkey P450 2C18 drug metabolizing enzyme and the open reading frame of the sequence of the cynomolgus monkey P450 oxidoreductase. The sequence or the complementary sequence of the cynomolgus monkey P450 oxidoreductase is shown in SEQ ID NO:2. Protein which is expressed by a heterogeneous source of the invention only represents the cynomolgus monkey P450 2C18 hypotype and the system is closer to the real situation of metabolism in vivo of cynomolgus monkeys.

The invention provides an optimized cynomolgus mononuclear cell separation method, which specifically comprises the following steps: obtaining monkey blood, adding hydroxyethyl starch, uniformly mixing and settling the blood for 20 minutes; diluting the ficoll solution with a DPBS solution; preparing a 50 ml centrifugal tube, and adding 20 ml of the diluted ficoll solution; slowly adding 20ml of settled monkey blood into the ficoll solution, and paying attention to keep the interface clear; centrifuging the blood at 20 DEG C under 600 g for 30 min, and performing standing treatment; discarding an upper serum layer, collecting a third leukocyte layer, and transferring the third leukocyte layer into another centrifugal tube; adding a DPBS solution to 50 ml, and performing 450 g centrifugation for 10 min to wash away the impurities; and re-suspending the cell precipitate, and counting the cells. In the invention, the simple technical system for separating the PBMC from the peripheral blood of the cynomolgus monkey is established, wherein the experiment cost can be reduced.

The invention provides a method for constructing a diabetic primate model. The method is to inject streptozotocin into cynomolgus monkeys according to the method of small dose increasing, and feed high-sugar and high-fat feed at the same time. , increasing nocturnal light to induce cynomolgus monkeys to become a model of diabetes. Using this method, a diabetic monkey model was successfully established for 1.5 to 6 months. The model has two core characteristics of diabetes, insulin resistance and hyperglycemia, and the hyperglycemia lasts for a long time, and has not decreased for more than 200 days. The animal model established by the present invention can be used in animal experiments with a longer duration, and can be sold as a mature animal model to generate economic benefits.

The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and / or Variable Heavy Chain (VH) Domains that have been humanized and / or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.

The invention discloses SNP markers for identifying cynomolgus monkey origin (subpopulation), and applications thereof. The SNP marker comprises 48 SNP sites including SNP1 to SNP48 which respectively represents 61th site of nucleotide sequences shown by SEQ ID NO:1 to SEQ ID NO:48. 48 SNP markers for identifying the cynomolgus monkey origin (subpopulation) can be developed by utilizing the advantages of biological information technology, and the application of the SNP markers can greatly reduce the cost and simplify the operations for identifying the true origin of the imported cynomolgus monkey origin (subpopulation). The applications of the SNP markers can achieve the purposes of rapidly performing primary screening and lowering the detection cost, so that the standardized progress for identifying the cynomolgus monkey origin (subpopulation) can be promoted.

The invention belongs to the technical field of biology and new medicine, and discloses a feed-layer-free culture method for cynomolgus monkey stem cells. The feed-layer-free culture method comprises the following steps: digesting pluripotent stem cells cultured in a feed layer with collagenase, respinning the digested cells with a feed-layer-free culture medium, transferring the cells into a culture dish coated with matrigel in advance, and putting the culture dish into an incubator; and when the cell density is 80%-90% of the area of the culture dish, digesting the cells with ACCTUSE enzyme, and transferring the cells into the culture dish coated in advance according to the ratio of (1: 5)-(1: 10). According to the method, new culture conditions are developed, so that the cynomolgus monkey pluripotent stem cells can be cultured under the condition of no feed layer, a lot of manpower and material resources are saved without preparation of the feed layer, culture components are definite, and the pluripotency of the cynomolgus monkey pluripotent stem cells can be kept for a long time. The feed-layer-free culture method for cynomolgus monkey stem cells is free of influence of batch detection, the accuracy of experiments can be improved, and a culture system can be clinically used for reference.

The invention discloses a tandem epitope polypeptide vaccine of a novel coronavirus and application of the tandem epitope polypeptide vaccine. Specifically, the invention provides a novel coronavirus pneumonia vaccine polypeptide based on analysis and research of RBD sequence and structural information of S protein of SARS-CoV-2, and the vaccine polypeptide comprises the following elements connected in series: a universal Th epitope sequence, a B cell epitope sequence and a T cell epitope sequence, wherein the B cell epitope and the T cell epitope have amino acid sequences from an RBM region of S protein of SARS-CoV-2. The invention further provides a vaccine composition containing the vaccine polypeptide and application of the vaccine composition. Experiments show that the vaccine polypeptide can enable cynomolgus monkeys to start relatively strong cell and humoral immunity, generates a neutralizing antibody for blocking the combination of RBD and ACE2, and can be used for preventing and treating novel coronavirus pneumonia.

The present disclosure relates to CDR defined antibodies targeting the 5T4 oncofoetal antigen (TPBG, 5T4, Wnt Activated Inhibitory Factor 1, WAIF1) which exhibit a binding affinity for human 5T4 antigen which is in the same order of magnitude as their affinity for cynomolgus monkey 5T4. Antibody-drug conjugates (ADCs), and their use in the treatment of human solid tumours and haematological malignancies are claimed.

The invention provides an IL5 nanobody and application thereof. Specifically, the invention provides the IL5 nanobody. The invention also provides a coding sequence for coding the nanobody, a corresponding expression vector, a host cell capable of expressing the nanobody, and a production method of the nanobody. The nanobody can specifically recognize IL5 of human beings and cynomolgus monkeys, does not recognize IL5 of mice, and has good binding activity; the nanobody disclosed by the invention has good IL5 / IL5R blocking activity, and the blocking activity is obviously superior to that of a control antibody Nucala; the nanobody can effectively inhibit proliferation of IL5-induced TF-1 cells, and the inhibition activity of the nanobody is superior to that of the control antibody Nucala; and the expression yield of the nanobody in pichia pastoris can reach 13 g / L, and the purity of target protein expression is high.

The invention relates to a method for detecting directional distribution of human mesenchymal stem cells in an animal body, DNA concentration of hPCMSC human placenta chorionic mesenchymal stem cell injection on peripheral blood and organ tissue samples of a cynomolgus monkey collected in a test is detected by a fluorescence quantitative PCR method (Polymerase Chain Reaction) method, and the cellnumber is calculated. The method can be used for evaluating the safety after the human mesenchymal stem cells are implanted into the animal body. The method for tracing the directional distribution ofthe human mesenchymal stem cells implanted into the animal body is a cell distribution detection method which integrates the advantages of safety, sensitivity, specificity, non-invasiveness, persistence and the like into a whole in an animal experiment.

The invention relates to a liquid feed and method for constructing a cynomolgus monkey alcoholic liver disease model. The liquid feed comprises a liquid feed A and a liquid feed B which respectively contain specific components. According to the cynomolgus monkey alcoholic liver disease model construction method, cynomolgus monkey alcoholic liver disease modeling is performed through a progressivetransition manner of sequentially adopting the combination of conventional solid feed and the liquid feed B, the combination of the liquid feed B and the liquid feed A, and the liquid feed A. The liquid feed more fit the human alcoholic liver disease occurrence environment, anorexia, dehydration, poor state and other situations of modeling animals can be effectively avoided, and thereby the modeling success rate is improved.

The invention aims at improving cynomolgus magnetic resonance scanning methods and consequently providing legible brain magnetic resonance images. The invention provides a cynomolgus magnetic resonance scanning method that utilizes a Philips Intera A chiva 3.0T magnetic resonance machine for scanning, a T1 scanning sequence is IR with the visual field of 120mm, the TR / TE of 2153ms / 13ms, the seam thickness / interval of 3mm / 0.3mm and the matrix of 256 multiplied by 256, while a T2 weighted image scanning sequence is SE with the visual field of 12cm multiplied by 12cm, the TR / TE of 3200ms / 102ms, the seam thickness / interval of 3mm / 0.3mm and the matrix of 256 multiplied by 256. The cynomolgus magnetic resonance scanning method can provide legible brain magnetic resonance images, and has greatersignificance in the displaying of cynomolgus craniocerebral anatomical structure and cytological marking and magnetic resonance tracing after brain transplantation.