The invention relates to the field of compounds, especially peptides or polypeptides, that have thrombopoietic activity. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Provided herein are polypeptides, compositions, and methods for treating a cancer in an individual using a polypeptide comprising a thrombopoietin domain and a Flt3 ligand domain. Also provided herein are nucleic acids encoding such polypeptides, expression vectors and cells comprising such nucleic acids, and methods of producing the polypeptides comprising a thrombopoietin domain and a Flt3 ligand domain. The administration of a fusion polypeptide comprising a thrombopoietin domain and a Flt3 ligand domain to a subject may treat and reduce the symptoms of hematopoietic failure, including thrombopenia, and/or acute radiation syndrome.

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.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.