Regeneron Pharmaceuticals, Inc.

Duke University

Regeneran Pharmaceuticals, Inc.

Karolina Meagher

Andrew J Murphy

Lynn Macdonald

Cagan Gurer

Sean Stevens

John R McWhirter

Naxin Tu

Brinda Prasad

George D Yancopoulos

Aris I Baras

Garnett Kelsoe

Peter W Mason

Ying Hu

Israel Lowy

Alexander O Mujica

Vera Voronina

Stanley J Wiegand

Lori C Morton

Jingtai Cao

Adrianna Latuszek

John Mcwhirter

Barton F Haynes

Kishor Devalaraja-Narashimha

Yifan Luo

Cong Huang

Sarah Casanova

Andrew Murphy

Alexander Mujica

Stanley Wiegand

Disclosed herein are genetically modified rodent animals comprising in their genome a nucleic acid which comprises a nucleotide sequence encoding a human CR1 polypeptide, wherein the rodent animals display a human-like expression of the human CR1 polypeptide. Also disclosed herein are isolated rodent cells including rodent embryonic stem cells, and rodent tissues. Further disclosed are nucleic acid vectors and methods for making the genetically modified rodent animals, as well as methods of using such genetically modified rodent animals for screening and testing candidate compounds.

Rodent animals expressing human CR1

The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.

Genetically modified T cell receptor mice

Genetically modified mice and methods and compositions for making and using the same are provided, wherein the genetic modification comprises humanization of an Fc&#x3b3;RI protein.

Non-human animals having humanized Fc-gamma receptors

Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

Non-human animals expressing humanized C1Q complex

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

Mice that make Vbinding proteins

According to certain embodiments, the present disclosure provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds aspecies target antigen and a second antigen binding domain that binds a complement component. In certain embodiments, the bispecific antigen-binding molecules of the present disclosure are capable of binding to thespecies target antigen with an ECof about 10 nM or less, and/or are capable of promoting complement deposition on thespecies with an ECof about 10 nM. The antibodies of the disclosure are useful for treating diseases in which inhibition or reduction of the growth of aspecies is desired and/or therapeutically beneficial, for example, for treating staphylococcal infections including a skin infection, cellulitis, pneumonia, meningitis, urinary tract infection, toxic shock syndrome, endocarditis, osteomyelitis, bacteremia, or sepsis, or for preventing or treating ainfection that occurs as a result of a surgical procedure.

Bispecific antigen-binding molecules that bind atarget antigen and a complement component and uses thereof

Provided herein, inter alia, are non-human animals comprising nucleic acid sequences encoding a C3 protein that comprises a human sequence as well as transgenic non-human animals comprising a C3 gene that is human in whole or in part as well as methods for using the same to screen for candidate therapeutic molecules to treat complement-related nephropathies. Also provided herein are methods for improving kidney function in an individual diagnosed with or thought to have a complement-related nephropathy.

Humanized model of kidney and liver disorders

Non-human animals with humanized immunoglobulin loci and methods of using them in vaccine design are described, as well as methods for making broadly neutralizing antibodies against infectious agents and pathogens are provided. Non-human animals with humanized immunoglobulin loci used in B-cell-lineage immunogen design in vaccine development are provided, as are methods of carrying out such design.

B cell lineage based immunogen design with humanized animals

Genetically modified mice are provided that express human &#x3bb; variable (hV&#x3bb;) sequences, including mice that express hV&#x3bb; sequences from an endogenous mouse &#x3bb; light chain locus, mice that express hV&#x3bb; sequences from an endogenous mouse &#x3ba; light chain locus, and mice that express hV&#x3bb; sequences from a transgene or an episome wherein the hV&#x3bb; sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human &#x3bb; variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human &#x3bb; variable sequences, including human antibodies, are provided.

Human lambda light chain mice

Non-human animals, e.g., mammals, e.g., mice or rats, are provided comprising an immunoglobulin heavy chain locus that comprises a rearranged human immunoglobulin heavy chain variable region nucleotide sequence. The rearranged human immunoglobulin heavy chain variable region nucleotide sequence may be operably linked to a heavy or light chain constant region nucleic acid sequence. Also described are genetically modified non-human animals comprising an immunoglobulin light chain locus comprising one or more but less than the wild type number of human immunoglobulin light chain variable region gene segments, which may be operably linked to a light chain constant region nucleic acid sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a heavy chain.

Non-human animals with modified immunoglobulin heavy chain sequences

Mice having a restricted immunoglobulin heavy chain locus are provided, wherein the locus is characterized by a single polymorphic human Vgene segment, a plurality of human Dgene segments and a plurality of Jgene segments. Methods for making antibody sequences that bind an antigen (e.g., a viral antigen) are provided, comprising immunizing a mouse with an antigen of interest, wherein the mouse comprises a single human Vgene segment, a plurality of human Dgene segments and a plurality of Jgene segments, at the endogenous immunoglobulin heavy chain locus.

Growing community of inventors

Tarrytown, NY, United States of America

Karolina Meagher