Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

The present invention relates to recombinant optimized polynucleotide encoding a cytokine or cytokine receptor and to methods of making a recombinant optimized polynucleotide encoding a cytokine or cytokine receptor.

A novel and thermostable lyophilized pharmaceutical composition of Romiplostim (Fcpeptide fusion protein) along with buffer, bulking agent, stabilizer, and surfactant at pH range of 4.0-6.0.

This invention provides a range of translatable messenger UNA (mUNA) molecules. The mUNA molecules can be translated in vitro and in vivo to provide an active polypeptide or protein, or to provide an immunization agent or vaccine component. The mUNA molecules can be used as an active agent to express an active polypeptide or protein in cells or subjects. Among other things, the mUNA molecules are useful in methods for treating rare diseases.

A method for treating a defect site in a living bone of an animal by applying an exogenous compound having thrombopoietic activity to the defect site in an amount effective to induce thrombopoiesis. The exogenous compound activates a thrombopoietin receptor, leading to accelerated bone formation at the defect site. Also provided is a method for repairing a segmental bone defect in an animal bone by inserting into the segmental bone defect a biodegradable bone repair scaffold that contains a compound having thrombopoietic activity. The compound activates a thrombopoietin receptor and accelerates bone formation such that bridging occurs at the segmental bone defect.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

The present invention relates to new methods for the purification of Fc-peptide fusion protein (peptibodies) derived from inclusion bodies after prokaryotic expression. In particular, it relates to chromatographic methods of the fusion peptides after refolding and dimerization comprising affinity capture, intermediate and polishing chromatographies. These methods facilitate the decrease of product-related impurities, such as sulfide variants or charge variants of the Fc-peptide fusion proteins in the final product. In addition, the present invention relates to specific conditions and selected buffers avoiding aggregation, precipitation, and degradation of the Fc-peptide fusion proteins. Finally, the methods of the present invention result in a formulated pharmaceutical composition or a pre-stage pharmaceutical composition containing an Fc-peptide fusion protein of high purity.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.