The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

The present invention provides cells, transgenic animals, including transgenic mammals and particularly rodents comprising engineered immunoglobulin (Ig) alleles. Such engineered alleles, wherein an Ig light chain CL exon [Cκ or Cλ (Cλ1, Cλ2 or Cλ3)] is incorporated into the Ig heavy chain locus, are capable of producing heavy chain-only antibodies as a single chain VH antibody (scVHAb) or heavy chain antibody (HCAb) comprising two extended scVHAbs. The scVHAb comprises an antigen-binding part consisting of a VH domain and the immunoglobulin constant domains CL, which is either Cκ or Cλ, and CH1, in the order from N-terminus to C-terminus: VH-L1-CL-L2-CH1, wherein L1 and L2 are each, independently, peptidic linkers; and wherein CL is paired with CH1 through beta-sheet contact thereby obtaining a CL/CH1 dimer.

This invention relates to a transgenic animal model for testing immunogenicity and protective efficacy of human vaccines and the method for generating such a multi-transgenic animal. This invention also relates to methods for screening compositions for human vaccine development. More specifically, the present invention relates to a mouse model capable of expressing human leukocyte antigens DR4 and A2, and/or human costimulatory molecules (CD80) which upon infusion of human HLA-matched hematopoietic stem cells develop a functional human immune system able to respond to vaccination with human vaccines. The invention also relates to method of producing human antibodies specific for a desired antigen using the transgenic mouse.

The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising the antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in the methods.

The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.

The present disclosure relates to a transgenic non-human mammal (e.g., mouse) that expresses a common light chain, wherein the transgenic non-human mammal comprises a hybrid light chain locus from which a light chain having a human Vκ joined to a mouse Jκ is expressed. Also provided are methods of making a transgenic non-human mammal capable of expressing a common light chain.

The present invention relates to transgenic ornamental barbs, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic barbs and methods of providing them to the ornamental fish industry for the purpose of marketing.

The present disclosure provides compositions and methods related to the generation and use of transgenic animal models having stem cell reporter systems. In particular, the present disclosure provides a novel transgenic animal model that expresses a nuclear-localized fluorescent reporter in cells endogenously expressing a leucine-rich repeat-containing G-protein coupled receptor (LGR) gene (e.g., LGR5gene). Given the role of LGR genes in stem cell and cancer biology, the transgenic animal models provided herein are useful for a wide range of therapeutic and diagnostic purposes.

The disclosure in the specification relates to an artificial recombinant chromosome and the use thereof, and more particularly to an artificial recombinant chromosome generated by the recombination of two or more chromosomes and a production of a transgenic animal using a cell including the same. Especially, in the disclosure in the specification, an interchromosomal exchange between the recipient chromosome and the donor chromosome has many merits to produce the artificial recombinant chromosome for producing the transgenic animal.

A method of obtaining a nucleotide sequence, from an immunized genetically modified non-human mammal, encoding an immunoglobulin variable domain of an antibody specific for a particular antigen is disclosed. A method for making antibodies against a particular antigen is also disclosed.