Provided are compositions and methods for producing modified non-human animals that produce heavy chain only antibodies (HCAbs), and modified non-human animals produced by the compositions and methods, and isolated HCAbs produced by the HCAbs.

Disclosed herein are rodents (such as mice and rats) genetically modified at an endogenous Scn9a locus to comprise an exogenous Scn nucleotide sequence such as the coding sequence of a human SCN2A gene. Also disclosed are methods and compositions useful for making such rodents, and methods of using such rodents for generating anti-NaV1.7 antibodies.

The present invention provides transgenic animals comprising some or all components of a human heavy and/or light chain immunoglobulin variable region locus, methods of making such animals, methods of making human antibodies using such animals, and methods of treatment using the human antibodies made in such animals, wherein the animals comprise in their genome a plurality of human heavy chain V gene segments all of which are immediately preceded by the same first leader peptide-encoding sequence, and/or a plurality of human light chain V gene segments all of which are immediately preceded by the same second leader peptide-encoding sequence, or both. The invention also provides polynucleotide constructs comprising two or more human heavy or light chain leader/V gene segments comprising identical leader peptide-encoding sequences. Such animals, constructs and methods find use in efficient generation of optimally diverse populations of antibodies against antigens of interest, such as antigens of therapeutic interest.

One variation of a method includes: during an initial period, modifying a population of insects to produce a target compound responsive to application of a stressor; during a growth period succeeding the initial period, cultivating the population of insects according to a set of growth conditions; and, during a treatment period succeeding the growth period, applying a dosage of the stressor to the population of insects to trigger production of the target compound. The method further includes, during a harvest period succeeding the treatment period: harvesting the population of insects; homogenizing the population of insects to form a blend including a set of secondary components and an amount of the target compound; extracting the amount of the target compound from the blend; and mixing the first amount of the first target compound with a set of stabilizing agents configured to stabilize the target compound.

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

Provided is a genetically modified non-human mammal that comprises an anchor DNA sequence inserted at an endogenous locus of a secretory milk protein gene, wherein the anchor DNA sequence comprises a site-specific recombinase recognition site. Also provided is a genetically modified non-human mammal that comprises a transgene inserted at an endogenous locus of a secretory milk protein gene, wherein the transgene encodes a secretory protein and is operably linked to the endogenous promoter of said secretory milk protein gene, and wherein the transgene is flanked by a pair of site-specific recombinase resulting sites. The genetically modified non-human mammals provided can be used for producing the secreted recombinant protein encoded by the transgene from the milk produced by the genetically modified non-human mammals.

The invention relates to nucleic acid constructs for expression in mice for the reproduction of heavy chain only antibodies and V.sub.H domains, transgenic mice, related methods and uses.

Problem to be Solved: The present invention is intended to provide a polynucleotide encoding the light-chain variable region and the heavy-chain variable region of an anti-dog IgE antibody; and an anti-dog IgE antibody containing these variable regions. Solution: The present invention is DNA encoding a heavy-chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 2 or 6 and DNA encoding a light-chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 4 or 8, and an anti-dog IgE monoclonal antibody which binds to dog IgE, containing these variable regions or a functional fragment thereof which binds to dog IgE.

The present invention provides an anti-IGF-I receptor antibody that binds specifically to an IGF-I receptor of a vertebrate and has the proliferation-inducing activity of a vertebrate-derived cell, or a fragment thereof, or derivatives of these.

The present invention is based, in part, on the identification of novel antibodies that have binding affinity for both PD-L1 and PD-L2 and methods of using same. In one aspect, an isolated monoclonal antibody, or antigen-binding fragment thereof, which specifically binds both PD-L1 and PD-L2, is provided. In one embodiment, both PD-L1 and PD-L2 are human PD-L1 and human PD-L2.