A61K49/0008

Genetically modified mouse with humanized immunoglobulin heavy chain constant region genes and method of using

Provided herein are methods and compositions related to the in vivo testing of therapeutic agents comprising a human Fc in genetically modified rodents (e.g., the testing of the pharmacokinetic and/or pharmacodynamic properties of such a therapeutic agent in genetically modified rodents). In some embodiments the genetically modified rodents express antibodies comprising a human Fc (e.g., a human IgG1 Fc, a human IgG4 Fc). In some embodiments, the rodents express fully human antibodies (i.e., antibodies having human heavy chains and human light (γ or κ) chains). In certain embodiments the genetically modified rodents comprise one or more Fc receptors with a human extracellular domain (e.g., a Neonatal Fc Receptor (FcRn), a β-2-microglobulin polypeptide (β2M), a Fc ε receptor 1α (FcεR1α), a Fc γ receptor 1 alpha (FcγR1a), a Fc gamma receptor 2a (FcγR2a), a Fc gamma receptor 2b (FcγR2b), a Fc gamma receptor 3a (FcγR3a), a Fc gamma receptor 3b (FcγR3b), a Fc gamma receptor 2c (FcγR2c)). The transmembrane and cytoplasmic domain of such receptors can be human or non-human (e.g., rodent).

Genetically modified non-human animals and methods of use thereof

Genetically modified non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome are provided. Also provided are methods for making non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome, and methods for using non-human animals expressing human SIRPα and human IL-15 from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human T cell and/or natural killer (NK) cell development and function, in modeling human pathogen infection of human T cells and/or NK cells, and in various in vivo screens.

TREATMENT OF PROGRESSIVE SUPRANUCLEAR PALSY

Therapeutic methods and medicines may be developed by identifying a gene responsible for progressive supranuclear palsy, as may effective therapeutic methods and medicines. A medicine for progressive supranuclear palsy may contain a compound for inhibiting the expression of a filamin-A gene is provided. Also provided is an assessment system that uses cells expressing filamin-A, which is used in the search for medicaments for progressive supranuclear palsy or their candidates.

E2F reporter melanoma cells
11571483 · 2023-02-07 · ·

A modified melanoma cell line capable of quantification of the effects of MEK inhibitors and CDK4/6 inhibitors in a quantitative, temporal and non-invasive manner both in vitro and in vivo.

NON-HUMAN ANIMALS COMPRISING A HUMANIZED ALBUMIN LOCUS

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

SEMI-SOLID FORMULATION FOR VOLUNTARY ORAL ADMINISTRATION OF BIOACTIVE COMPOUNDS TO RODENTS

A formulation for voluntary oral administration of bioactive compounds to rodents. The semidsolid formulation having at least one thickening agent, a digestible sweetener selected from sucralose and calcium saccharin, a diluent agent, wherein the diluent agent is a powder with a granulometry between 300 and 800 μm, obtained from finely grounded seeds, cereal grains or cereal grain based diet for rodents, at least one flavor masking agent and a bioactive compound. The semi-solid formulation promotes voluntary feeding in rodents regardless of the bioactive compounds contained therein and without disruption of the metabolic pathways, therefore the semi-solid formulation has shown to be ideal for use in the oral administration of drugs and bioactive compounds to rodents. Use of the semi-solid formulation in the production of toxicant baits for rodents is also envisioned.

METHOD FOR CREATING A RENAL INJURY MODEL TO SCREEN MOLECULES FOR THE TREATMENT OF RENAL INJURY

The present invention is related to short-term renal injury models and methods for creating these models. The models and methods can be used for identifying, testing or characterizing candidate molecules with respect to their suitability to treat renal injury. The methods comprise a step of inducing, in a test subject, renal injury by administering subcutaneously a bolus of a renal injury inducer, in a dosage sufficiently high to induce renal injury. Different types of readout for renal injury are provided such as albumin creatinine ratio (ACR) determined in a urine sample taken from the subject, or the development of transcutaneous fluorescence after injection of a fluorescent molecule. Based on the readout the degree of renal injury and/or alteration of GFR can be determined.

NON-HUMAN ANIMALS COMPRISING A HUMANIZED ACE2 LOCUS
20230232796 · 2023-07-27 ·

Non-human animal cells and non-human animals comprising a humanized ACE2 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized ACE2 locus express a human ACE2 protein or a chimeric ACE2 protein, fragments of which are from human ACE2. Methods are also provided for using such non-human animals comprising a humanized ACE2 locus to assess in vivo ACE2 activity, e.g., coronavirus infection and/or the treatment or prevention thereof.

USE OF SYNAPTOTAGMIN-7 IN THE DIAGNOSIS AND TREATMENT OF BIPOLAR DISORDER
20230003717 · 2023-01-05 ·

Provided is a biomarker for bipolar disorder, comprising Syt7 gene and/or an expression product thereof. Also provided is use of the Syt7 gene and/or the expression product thereof in the preparing a medicament for treating bipolar disorder. By monitoring the Syt7 gene and/or the expression product thereof, medicaments for treating bipolar disorder can be screened, thus providing support for diagnosis and treatment targeting Syt7 molecules.

A HYPERTENSION ANIMAL MODEL AND METHODS OF USE
20230233713 · 2023-07-27 ·

The invention is directed to a hypertension animal model, and methods of using the same to induce heart failure with preserved ejection fraction (HFpEF) responses.