78 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 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 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.

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 relates to antibody molecules and antigen-binding portions thereof which bind specifically to CD47 (Cluster of Differentiation 47, also known as integrin associated protein [IAP]). In aspects of the invention, the anti-CD47 antibody molecules and antigen-binding portions thereof specifically bind to human CD47 and cynomolgus monkey CD47. Medical uses of the anti-CD47 antibody molecules and antigen-binding portions of the invention are disclosed. The anti-CD47 antibody molecules and antigen-binding portions of the invention represent modified and optimised binding molecules compared with a VxP037 murine / humanized anti-CD47 antibody described in WO2014 / 093678A2.

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

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 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 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 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.