公开(公告)号：WO2022056276A1

公开(公告)日：2022-03-17

申请号：PCT/US2021/049887

申请日：2021-09-10

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： LIU, Yashu ,  GUO, Chunguang ,  ZHANG, Qian ,  LEVENKOVA, Natasha ,  MURPHY, Andrew J. ,  OLSON, William

IPC: C07K16/00 ,  A01K67/027 ,  C07K16/28 ,  C07K16/46 ,  C12Q1/6872 ,  G16B30/10

Abstract: A method of obtaining a nucleotide sequence, from an immunized genetically modified non-human mammal, encoding an immunoglobulin variable domain of an antibody specific for a particular antigen is disclosed. A method for making antibodies against a particular antigen is also disclosed.

公开(公告)号：WO2022212582A1

公开(公告)日：2022-10-06

申请号：PCT/US2022/022653

申请日：2022-03-30

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： GUO, Chunguang ,  TU, Naxin ,  MURPHY, Andrew, J.

IPC: A01K67/027 ,  C07K14/73 ,  C07K14/725 ,  C07K14/705 ,  C07K14/74 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0325 ,  A01K2267/0337 ,  A01K2267/0387 ,  A01K67/0275 ,  A01K67/0278 ,  C07K14/7051 ,  C07K14/70514 ,  C07K14/70517 ,  C07K14/70539

Abstract: Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized T cell co-receptor (e.g., humanized CD4 and/or CD8 (e.g., CD8α and/or CD8β)), a human or humanized T cell receptor (TCR) comprising a variable domain encoded by at least one human TCR variable region gene segment and/or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and/or MHC II β chains) and/or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses at least one humanized T cell co-receptor (e.g., humanized CD4 and/or CD8), at least one humanized MHC that associates with the humanized T cell co-receptor (e.g., humanized MHC II and/or MHC I, respectively) and/or the humanized TCR are also provided. Methods for using the genetically engineered animals that mount a substantially humanized T cell immune response for developing human therapeutics are also provided.

公开(公告)号：WO2018064600A1

公开(公告)日：2018-04-05

申请号：PCT/US2017/054551

申请日：2017-09-29

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： HESLIN, David ,  ALLY, Roxanne ,  SIAO, Chia-Jen ,  LAI, Ka-Man, Venus ,  VALENZUELA, David, M. ,  GUO, Chunguang ,  LACROIX-FRALISH, Michael ,  MACDONALD, Lynn ,  SHARMA, Aarti ,  KAJIMURA, Daisuke ,  DROGUETT, Gustavo ,  FRENDEWEY, David

IPC: A01K67/027 ,  C12N15/90 ,  C12N15/113

Abstract: A non-human animal (e.g., a rodent) model for diseases associated with a C9ORF72 heterologous hexanucleotide repeat expansion sequence is provided, which non-human animal comprises a heterologous hexanucleotide repeat (GGGGCC) in an endogenous C9ORF72 locus. A non-human animal disclosed herein comprising a heterologous hexanucleotide repeat expansion sequence comprising at least one instance, e.g., repeat, of a hexanucleotide (GGGGCC) sequence may further exhibit a characteristic and/or phenotype associated with one or more neurodegenerative disorders (e.g., amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), etc.). Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)) are also provided.

Abstract translation: 提供了与C9ORF72异源六核苷酸重复扩增序列相关的疾病的非人动物（例如啮齿动物）模型，所述非人动物包含异源六聚核苷酸 在内源性C9ORF72基因座中重复（GGGGCC）。 本文公开的包含包含六核苷酸（GGGGCC）序列的至少一个实例，例如重复序列的异源六核苷酸重复扩增序列的非人动物还可以表现出与一种或多种神经变性病症（例如， 肌萎缩侧索硬化（ALS）和/或额颞叶痴呆（FTD）等）。 还提供了可用于预防，延缓或治疗一种或多种神经变性（例如，肌萎缩侧索硬化（ALS，也称为Lou Gehrig病）和额颞痴呆（FTD））的治疗候选物的方法。

公开(公告)号：WO2019113065A1

公开(公告)日：2019-06-13

申请号：PCT/US2018/063841

申请日：2018-12-04

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： MURPHY, Andrew J. ,  MACDONALD, Lynn ,  GUO, Chunguang ,  MCWHIRTER, John

IPC: A01K67/027 ,  C07K16/00 ,  C07K16/46 ,  C12N9/12

Abstract: Non-human animals (and/or non-human cells) and methods of using 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 immunoglobulin (Ig) light chains characterized by the presence of human Vλ domains. Non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Vλ light chains that are encoded by human Igλ light chain-encoding sequences inserted into an endogenous Igκ light chain locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and mouse constant regions.

公开(公告)号：WO2017214089A1

公开(公告)日：2017-12-14

申请号：PCT/US2017/036071

申请日：2017-06-06

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： MACDONALD, Lynn ,  VORONINA, Vera ,  GUO, Chunguang ,  MCWHIRTER, John ,  MURPHY, Andrew, J.

IPC: A01K67/027 ,  C07K16/00 ,  C07K16/46 ,  C12N9/64

CPC classification number: A01K67/0278 ,  A01K2207/15 ,  A01K2217/07 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/00 ,  C07K16/462 ,  C07K2317/10 ,  C07K2317/20 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/515 ,  C07K2317/52 ,  C12N9/6489 ,  C12N2800/30 ,  C12Y304/24046

Abstract: In certain aspects provided herein are non-human animals that express antibodies having human Vκ and νλ domains. In some embodiments, the ratio of antibodies containing human Vκ domains to antibodies containing human νλ domains is similar to that which occurs in humans.

Abstract translation: 在此提供的某些方面是表达具有人Vκ和Vλ结构域的抗体的非人动物。 在一些实施方案中，含有人Vκ结构域的抗体与含有人Vλ结构域的抗体的比例与人中发生的相似。

公开(公告)号：WO2018128691A8

公开(公告)日：2018-07-12

申请号：PCT/US2017/060006

申请日：2017-11-03

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： GUO, Chunguang ,  HARRIS, Faith ,  VORONINA, Vera ,  MCWHIRTER, John ,  LEVENKOVA, Natasha ,  MACDONALD, Lynn ,  TU, Naxin ,  MURPHY, Andrew, J.

IPC: A01K67/027 ,  C12N15/90 ,  C12N15/85 ,  C07K16/00

Abstract: 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.

公开(公告)号：WO2017210586A8

公开(公告)日：2017-12-07

申请号：PCT/US2017/035731

申请日：2017-06-02

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： MACDONALD, Lynn ,  MURPHY, Andrew, J. ,  GUO, Chunguang ,  LEVENKOVA, Natasha ,  TU, Naxin ,  MCWHIRTER, John ,  VORONINA, Vera ,  HARRIS, Faith

IPC: A01K67/027 ,  C12N9/12 ,  C07K16/00 ,  C07K16/46 ,  C12N15/90 ,  C12N15/85

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

公开(公告)号：WO2017210586A1

公开(公告)日：2017-12-07

申请号：PCT/US2017/035731

申请日：2017-06-02

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： MACDONALD, Lynn ,  MURPHY, Andrew, J. ,  GUO, Chunguang ,  LEVANKOVA, Natasha ,  TU, Naxin ,  MCWHIRTER, John ,  VORONINA, Vera ,  HARRIS, Faith

IPC: A01K67/027 ,  C12N9/12 ,  C07K16/00 ,  C07K16/46 ,  C12N15/90 ,  C12N15/85

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

Abstract translation: 本文提供了与表达外源性末端脱氧核苷酸转移酶（TdT）的非人动物有关的方法和组合物。

公开(公告)号：WO2020247623A1

公开(公告)日：2020-12-10

申请号：PCT/US2020/036114

申请日：2020-06-04

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： MCWHIRTER, John ,  HANSEN, Johanna ,  BABB, Robert ,  GUO, Chunguang ,  MACDONALD, Lynn ,  MURPHY, Andrew J.

IPC: A01K67/027 ,  C07K16/00

Abstract: The present disclosure provides, among other things, genetically modified non-human animals whose germline genome comprises an engineered endogenous immunoglobulin κ light chain locus comprising a single rearranged human immunoglobulin λ light chain variable region operably linked to a non-human Cλ gene segment, where the single rearranged human immunoglobulin λ light chain variable region comprises a human Vλ gene segment and a human Jλ gene segment. All immunoglobulin λ light chains expressed by B cells of the genetically modified non-human animal include human immunoglobulin λ light chain variable domains expressed from the single rearranged human immunoglobulin λ light chain variable region or a somatically hypermutated version thereof. Such animals, tissues from such animals, and cells from such animals represent an effective platform for producing antibodies, e.g., bispecific antibodies.

公开(公告)号：WO2019241692A1

公开(公告)日：2019-12-19

申请号：PCT/US2019/037285

申请日：2019-06-14

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： MURPHY, Andrew J. ,  MACDONALD, Lynn ,  GUO, Chunguang ,  MCWHIRTER, John ,  VORONINA, Vera

IPC: A01K67/027 ,  C12N15/85 ,  C12N5/10 ,  C12N5/12 ,  C07K14/705

Abstract: Non-human animals and methods and compositions for making and using them are provided, which non-human animals have a genome comprising an engineered or recombinant diversity cluster within an immunoglobulin heavy chain variable region, which engineered or recombinant diversity cluster comprises an insertion of one or more D H segments that are each operably linked to a 23-mer recombination signal sequence. Methods for producing antibodies from non-human animals are also provided, which antibodies optionally contain human variable regions and rodent, e.g., constant regions.