31 results about "Immunoglobulin genes" patented technology

This invention relates to humanized antibodies and antibody preparations produced from transgenic non-human animals. The non-human animals are genetically engineered to contain one or more humanized immunoglobulin loci which are capable of undergoing gene rearrangement and gene conversion in the transgenic non-human animals to produce diversified humanized immunoglobulins. The present invention further relates to novel sequences, recombination vectors and transgenic vectors useful for making these transgenic animals. The humanized antibodies of the present invention have minimal immunogenicity to humans and are appropriate for use in the therapeutic treatment of human subjects.

The invention relates to transgenic animals lacking endogenous Ig and capable of producing transgenic antibodies, as well as methods of making the same. The invention further relates to methods for producing transgenic antibodies in such animals, and transgenic antibodies so produced.

The invention is directed to a method of monitoring or detecting treatment-resistant clones in a patient being treated for a lymphoid or myeloid neoplasm from which patient-specific correlating clonotypes have been identified. In some embodiments, such method includes the steps of obtaining a sample from the patient comprising T-cells and/or B-cells; amplifying molecules of nucleic acid from the T-cells and/or B-cells of the sample, the molecules of nucleic acid comprising recombined DNA sequences from T-cell receptor genes or immunoglobulin genes; sequencing the amplified molecules of nucleic acid to form a clonotype profile; determining from the clonotype profile a level of each correlating clonotype and clonotypes clonally evolved therefrom; and correlating a presence of a treatment-resistant clone of the neoplasm with a change in relative levels of the correlating clonotypes and clonotypes clonally evolved therefrom. In part, the invention permits one to distinguish between cases where treatment is effective but insufficiently intense and cases where a cancer clone arises that is resistant to a current treatment approach.

The present invention provides oligonucleotides for detection of rearrangement of immunoglobulin genes for identifying clonality of cells, cancer cells, hypermutation in immunoglobulin gene, antibody isotype producing cell and/or assaying B cell repertoire in a sample. The oligonucleotides disclosed in the present invention are very specific to the immunoglobulin genes.

A medicament comprising a compound having an inhibitory action on Hsp90 or a pharmaceutically acceptable salt thereof as an active ingredient is used as a therapeutic agent for diseases associated with immunoglobulin gene translocations. In diseases associated with immunoglobulin gene translocations, abnormal enhancement of the expression of a partner gene in immunoglobulin gene translocation participates in the development of the diseases and the progress of the symptoms. By administering the compound having an inhibitory action on Hsp90 or a pharmaceutically acceptable salt thereof, degradation of protein encoded by the partner gene is promoted and the diseases can be treated.

The invention relates to a method of accelerating the induction of somatic mutations in vitro. The inventive method comprises the expression of at least one cDNA expressing a modified version of the AID gene in the cells to be mutated, in culture conditions and a medium that are suited thereto, said modified version resulting from an AID gene in which the three hydrophobic amino acids, leu189, phe193 and leu196, have been replaced by means of alanine mutations in each case. The invention can be used to induce mutations in Burkitt's lymphoma BL2. The invention can also be used to induce mutations in the immunoglobulin genes of immortalised antibody-producing cells, such as mouse hybridoma cells, human hybridoma cells or human B-cell lines immortalised by the Epstein-Barr virus (EBV).

A method for preparing an antigen-specific antibody by constructing a library of phage-displayed single chain variable fragment of an antibody with a novel frame-shifting PCR is disclosed. Also disclosed is a method for preparing a clone for producing an antigen-specific antibody.

The invention is directed to a method of monitoring a mantle cell lymphoma residual disease in an immunotransplant patient by post-treatment analysis of clonotype profiles from patient blood samples. In some embodiments, methods of the invention comprising steps of (a) treating a patient by immunotransplanting the patient with vaccine-primed autologous T cells; (b) obtaining a peripheral blood sample from the patient comprising B-cells and/or cell-free nucleic acids; (c) amplifying molecules of nucleic acid from the B-cells of the sample and/or cell-free nucleic acids in the sample, the molecules of nucleic acid comprising recombined DNA sequences from immunoglobulin genes; (d) sequencing the amplified molecules of nucleic acid to form a clonotype profile; and (e) determining from the clonotype profile a presence, absence and/or level of the one or more patient-specific clonotypes correlated with the mantle cell lymphoma, including phylogenic clonotypes thereof.

Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. These methods are useful for generating genetic diversity within immunoglobulin genes directed against an antigen of interest to produce altered antibodies with enhanced biochemical activity. Moreover, these methods are useful for generating antibody-producing cells with increased level of antibody production. The invention also provides methods for increasing the affinity of monoclonal antibodies and monoclonal antibodies with increased affinity.

A transgenic chicken is disclosed having disrupted endogenous immunoglobulin production. In one embodiment, a targeting construct is stably integrated into the genome of the chicken by homologous recombination in embryonic stem cells, and injection of the engineered embryonic stem cells into recipient embryos, thereby knocking out the endogenous immunoglobulin gene locus in resulting animals. The targeted disruption of the locus in embryonic stem cells is particularly useful in combination with the insertion of genetic elements encoding exogenous immunoglobulin molecules. After these chickens are cross-bred, a line of chickens is produced that has a reduction of endogenous immunoglobulin molecule production.

Provided are a B cell-derived iPS cell generated using a convenient technique, a technology for providing a human antibody at low cost using the iPS cell, an immunologically humanized mouse prepared using cells differentiated from the iPS cell, and the like. Also provided are a cloned cell obtained by contacting a B cell with nuclear reprogramming factors excluding C/EBPα and Pax5 expression inhibiting substances, particularly nucleic acids that encode Oct3/4, Sox2, Klf4 and c-Myc, wherein the cloned cell has an immunoglobulin gene rearranged therein and possesses pluripotency and replication competence (B-iPS cell). Still also provided are a method of producing a monoclonal antibody against a specified antigen, comprising recovering an antibody from a culture of B cells obtained by differentiating a B-iPS cell derived from a B cell immunized with the specified antigen, and a method of generating an immunologically humanized mouse, comprising transplanting to an immunodeficient mouse a human immunohematological system cell obtained by differentiating a B-iPS cell.

The present invention belongs to the field of biotechnology, and relates to a surface antigen 1 (SAG1) of Toxoplasma gondii human antibody Fab fragment, encoded gene and use thereof. According to the invention, the surface antigen 1 (SAG1) of Toxoplasma gondii human antibody Fab fragment is filtered from a base through establishing a Toxoplasma gondii human immunoglobulin, ELISA, diluting the prothrombin time, sequencing analysis, etc. Through expression purifying and authenticating, the human antigen Fab fragment is authenticated to specifically identify the tachyzoite-bradyzoite recombination SAG1 of Toxoplasma gondii and have higher affinity with the tachyzoite-bradyzoite recombination SAG1 of Toxoplasma gondii, for being identified with the specificity of Toxoplasma gondii tachyzoite-bradyzoite. The human antigen Fab fragment of the invention does not contain Fc segment and does not activate the alexin or cause the histopathological damages of human immune response, etc. when the function of restricting the invasion of Toxoplasma gondii to the host cell is exerted. The surface antigen 1 (SAG1) of Toxoplasma gondii human antibody Fab fragment is safe and reliable when applied for the human body. The antigen medicine for treating toxoplasmosis or the antigen targeted medicine can be prepared.

Genetically-modified mammals and immune cells are provided which are capable of producing or secreting detectably-labeled immunoglobulin molecules as a result of genetic modifications of at least one immunoglobulin gene in the genome thereof, such that a fusion polynucleotide encoding a detectable protein or peptide and an immunoglobulin component molecule is present.

The invention discloses a vector containing immunoglobulin gene, belonging to the field of molecular biology. The nucleotide sequence of the vector is shown in SEQID No.1. The invention also discloses a method for constructing the vector, and the vector can be used for remarkably prolonging the half life period of recombinant protein drug in vivo, thus prolonging the drug efficacy, reducing the times of medicine use of patients and lowering the cost.

The invention provides a primer group for amplifying a B lymphocyte immune repertoire and an application of the primer group. The primer group comprises a group of forward primers and a group of reverse primers. The forward primers comprise a linker sequence 1, a bar code sequence 1 and a specific sequence aiming at an immunoglobulin variable region complementation determining region 3, which areconnected in sequence from a 5' end to a 3' end, wherein the specific sequence aiming at the immunoglobulin variable region complementary determining region 3 is shown as any one of SEQ ID NO. 1 to SEQ ID NO. 12; and the reverse primers sequentially comprise a linker sequence 2, a bar code sequence 2 and a specific sequence aiming at an immunoglobulin gene constant region from the 5' end to the 3'end. The primer group is used for amplifying B lymphocytes of an IgAN patient and a normal control group, library information is collected, and the length and diversity changes of CDR3 of the IgAN patient are analyzed through sequencing.

This document provides methods and materials related to detecting gene rearrangements (e.g., MYC gene rearrangements). For example, nucleic acid probe sets for detecting MYC-immunoglobulin gene rearrangements in mammals are provided.

Compositions containing multiple different AAV stock are provided which allow for regulated expression of an immunoglobulin in a variety of tissues. Also provided is a method for regulating the dose of a pharmacologically active immunoglobulin. The method involves co-administering: (a) a first stock of recombinant AAV containing: an activation domain operably linked to expression control sequences comprising a promoter and a first nuclear localization signal; and a DNA binding domain comprising a zinc finger homeodomain and two or more FK506 binding protein domain (FKBP) subunit genes, wherein a first FKBP subunit gene and a second FKBP subunit gene have coding sequences which are no more than about 85% identical to each other, said DNA binding domain being operably linked to a second nuclear localization signal; and (b) a second stock of recombinant AAV comprising at least 2 to about 12 copies of a zinc finger homeodomain which are specific binding partners for the zinc finger homeodomain of the DNA binding domain, and further comprising at least one immunoglobulin expression cassette operably linked to inducible expression control sequences, such that when an effective amount of a rapamycin or rapalog is delivered transcription and expression of the immunoglobulin gene is induced.