Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Vera Voronina

Andrew J Murphy

Lynn Macdonald

Cagan Gurer

Naxin Tu

Sean Stevens

John R McWhirter

Faith Harris

Yingzi Xue

Chunguang Guo

Natasha Levenkova

David Frendewey

Ka-Man Venus Lai

Karolina Meagher

Gustavo Droguett

George D Yancopoulos

David M Valenzuela

Wojtek Auerbach

Brian Zambrowicz

Anthony Gagliardi

John Mcwhirter

Jesper Gromada

Marine Prissette

Corey Momont

Brinda Prasad

Jason Mastaitis

Ashok Badithe

Non-human animals (and/or non-human cells) and methods of using and making the same are provided, which non-human animals (and/or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). Non-human animals described herein express antibodies that contain human Igλ light chains, in whole or in part. In particular, non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Igλ light chains, in whole or in part, that are encoded by human Igλ light chain-encoding sequences inserted into an endogenous Igλ light chain locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided.

Non-human animals having an engineered immunoglobulin lambda light chain locus

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Genetically modified major histocompatibility complex mice

Described herein are anchor-modified immunoglobulin polypeptides, wherein the anchor moors the immunoglobulin polypeptide to a receptor of interest. The anchor-modified immunoglobulin polypeptides are generally characterized at the N-terminus with an anchor, e.g., the receptor binding portion of a ligand that binds a receptor. Non-human animals genetically modified with recombinant immunoglobulin segments that encode the anchor-modified immunoglobulin polypeptides are capable of making the anchor-modified immunoglobulin polypeptides. Such non-human animals also provided, along with methods and compositions for making and using the non-human animals. Methods for producing anchor-modified immunoglobulins from non-human animals are also provided, as well as anchor-modified immunoglobulins generated therefrom.

Nucleic acids encoding anchor modified antibodies and uses thereof

Methods and compositions are provided for generating antigen-binding proteins against a foreign antigen of interest.

Methods for producing antigen-binding proteins against foreign antigens

Provided herein are methods and compositions related to non-human animals that express exogenous Terminal Deoxynucleotidyltransferase (TdT).

Non-human animals expressing exogenous terminal deoxynucleotidyltransferase

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

Compositions and methods are provided for creating and promoting biallelic targeted modifications to genomes within cells and for producing non-human animals comprising the modified genomes. Also provided are compositions and methods for modifying a genome within a cell that is heterozygous for an allele to become homozygous for that allele. The methods make use of Cas proteins and two or more guide RNAs that target different locations within the same genomic target locus. Also provided are methods of identifying cells with modified genomes.

Methods and compositions for targeted genetic modification using paired guide RNAs

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 (&#x3b3; or &#x3ba;) 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 &#x3b2;-2-microglobulin polypeptide (&#x3b2;2M), a Fc &#x3b5; receptor 1&#x3b1; (Fc&#x3b5;R1&#x3b1;), a Fc &#x3b3; receptor 1 alpha (Fc&#x3b3;R1a), a Fc gamma receptor 2a (Fc&#x3b3;R2a), a Fc gamma receptor 2b (Fc&#x3b3;R2b), a Fc gamma receptor 3a (Fc&#x3b3;R3a), a Fc gamma receptor 3b (Fc&#x3b3;R3b), a Fc gamma receptor 2c (Fc&#x3b3;R2c)). The transmembrane and cytoplasmic domain of such receptors can be human or non-human (e.g., rodent).

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

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

Methods and compositions are provided for making one or more targeted genetic modifications at a target genomic locus within a cell and for producing non-human animals comprising the modified genomic locus. The methods employ two or more large targeting vectors which are capable of recombining with each other and with the target genomic locus in a single genomic targeting step. The methods may also be employed in combination with a nuclease agent. Methods and compositions are also provided for enhancing homologous recombination at a target genomic locus in a cell. The methods employ two or more nucleic acids comprising one or more overlapping sequences. The methods may be employed in combination with a nuclease agent or without a nuclease agent.

Methods and compositions for targeted genetic modification through single-step multiple targeting

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized &#x3b2;2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II &#x3b1; and &#x3b2; polypeptides), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized &#x3b2;2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of the human immune system are provided.

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Sleepy Hollow, NY, United States of America

Vera Voronina