公开(公告)号：US20130185821A1

公开(公告)日：2013-07-18

申请号：US13798310

申请日：2013-03-13

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Robert BABB ,  John MCWHIRTER ,  Lynn MACDONALD ,  Sean STEVENS ,  Samuel DAVIS ,  David R. BUCKLER ,  Karolina A. MEAGHER ,  Andrew J. MURPHY ,  Natasha LEVENKOVA

IPC: A01K67/027

CPC classification number: A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/00 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/515 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  C12N15/8509 ,  C12N2800/204

Abstract: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided. Bispecific antibodies capable of binding first and second antigens are provided, wherein the first and second antigens are separate epitopes of a single protein or separate epitopes on two different proteins are provided.

Abstract translation: 提供遗传修饰的小鼠，其中小鼠表达免疫球蛋白轻链总谱，其特征在于有限数量的轻链可变结构域。 提供的小鼠在其种系中仅来自有限谱系的一个或几个免疫球蛋白轻链可变结构域。 提供了使用如本文所述的小鼠制备具有通用轻链的双特异性抗体的方法，包括人轻链可变区。 提供了适合用于多特异性结合蛋白（例如双特异性抗体）和宿主细胞的人可变区的方法。 提供了能够结合第一和​​第二抗原的双特异性抗体，其中第一和第二抗原是单个蛋白质的分离表位或两种不同蛋白质上的分离表位。

公开(公告)号：US20130185819A1

公开(公告)日：2013-07-18

申请号：US13793812

申请日：2013-03-11

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Lynn MACDONALD ,  Andrew J. MURPHY ,  Cagan GURER ,  John MCWHIRTER ,  Vera VORONINA ,  Faith HARRIS ,  Sean STEVENS ,  Yingzi XUE

IPC: A01K67/027

CPC classification number: A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0387

Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide 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.

Abstract translation: 本发明提供表达嵌合人/非人MHC I多肽和/或人或人源化β2微球蛋白多肽以及包含其的胚胎，细胞和组织的遗传修饰的非人动物。 还提供了用于制备所述转基因动物的构建体及其制备方法。 提供了使用遗传修饰动物研究人体免疫系统各个方面的方法。

公开(公告)号：US20130109053A1

公开(公告)日：2013-05-02

申请号：US13661342

申请日：2012-10-26

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Lynn MACDONALD ,  Andrew J. MURPHY ,  John MCWHIRTER ,  Naxin TU ,  Vera VORONINA ,  Cagan GURER ,  Karolina MEAGHER ,  Sean STEVENS

IPC: A01K67/027 ,  C12P21/00 ,  A01K67/02

CPC classification number: A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0387 ,  C07K14/7051 ,  C07K2319/00 ,  C12N15/8509 ,  C12N2800/204 ,  C12N2800/30

Abstract: 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.

Abstract translation: 本发明提供了一种遗传修饰的非人动物，其在其基因组中包含未经修复的T细胞受体可变基因基因座，以及胚胎，细胞和包含该基因的组织。 还提供了用于制备所述转基因非人动物的构建体及其制备方法。 还提供了使用转基因非人动物的各种方法。

公开(公告)号：US20240341291A1

公开(公告)日：2024-10-17

申请号：US18760465

申请日：2024-07-01

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： John MCWHIRTER ,  Cagan GURER ,  Lynn MACDONALD ,  Andrew J. MURPHY

IPC: A01K67/0278 ,  C07K14/705 ,  C12N15/85 ,  G01N33/50

CPC classification number: A01K67/0278 ,  C07K14/70575 ,  C12N15/85 ,  G01N33/5088 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/07 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0325 ,  A01K2267/0381 ,  A01K2267/0387 ,  C07K2319/00 ,  G01N2500/10

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

公开(公告)号：US20220340652A1

公开(公告)日：2022-10-27

申请号：US17724381

申请日：2022-04-19

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Susan D. CROLL ,  Lynn MACDONALD ,  Andrew J. MURPHY

IPC: C07K16/22 ,  A61K39/395 ,  A61P29/02

Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that bind to human artemin. Methods for using anti-artemin antibodies and antigen-binding fragments are also provided.

公开(公告)号：US20220033847A1

公开(公告)日：2022-02-03

申请号：US17506730

申请日：2021-10-21

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Brinda PRASAD ,  Naxin TU ,  Karolina MEAGHER ,  Lynn MACDONALD ,  Andrew MURPHY ,  Sean STEVENS

IPC: C12N15/85 ,  C07K14/47 ,  A01K67/027

Abstract: 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.

公开(公告)号：US20170247474A1

公开(公告)日：2017-08-31

申请号：US15345161

申请日：2016-11-07

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： George D. YANCOPOULOS ,  Nicholas J. PAPADOPOULOS ,  Neil STAHL ,  Samuel DAVIS ,  Andrew J. MURPHY ,  Lynn MACDONALD

IPC: C07K16/46 ,  C07K16/28

CPC classification number: C07K16/468 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/2887 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/64

Abstract: Multivalent antigen-binding proteins comprising two or three or four or more immunoglobulin heavy chain variable domain binding domains are provided, as are methods for making them, nucleic acid constructs, and cell lines for making them. Proteins comprising two or three or four or more different heavy chain variable domains that lack an immunoglobulin variable domain are provided. Proteins comprising two or three or four or more different heavy chain variable domains that associate with the same immunoglobulin light chain variable domain are also provided.

公开(公告)号：US20150245598A1

公开(公告)日：2015-09-03

申请号：US14691175

申请日：2015-04-20

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Lynn MACDONALD ,  Andrew J. MURPHY ,  Naxin TU ,  Cagan GURER ,  Vera VORONINA ,  Sean STEVENS

IPC: A01K67/027 ,  C07K14/74

CPC classification number: A01K67/0278 ,  A01K2217/052 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/03 ,  A61K39/00 ,  C07H21/04 ,  C07K14/70539 ,  C12N15/8509 ,  C12N2830/001

Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II α and β 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.

Abstract translation: 本发明提供表达人源化MHC II蛋白（人源化MHCIIα和＆bgr;多肽）以及包含其的胚胎，细胞和组织的遗传修饰的非人动物。 还提供了用于制备所述转基因动物的构建体及其制备方法。 提供了使用遗传修饰动物研究人体免疫系统各个方面的方法。

公开(公告)号：US20150119556A1

公开(公告)日：2015-04-30

申请号：US14589249

申请日：2015-01-05

Applicant: Regeneron Pharmaceuticals, Inc.

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

IPC: C07K16/00

CPC classification number: A01K67/0275 ,  A01K67/0278 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/00 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/56 ,  C07K2317/92 ,  C07K2317/94 ,  C12N15/8509 ,  C12N2800/204

Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain variable domains derived from a limited repertoire of human immunoglobulin light chain variable gene segments that comprise histidine modifications in their germline sequence. Methods of making non-human animals that express antibodies comprising histidine residues encoded by histidine codons introduced into immunoglobulin light chain nucleotide sequences are provided.

公开(公告)号：US20130247235A1

公开(公告)日：2013-09-19

申请号：US13832309

申请日：2013-03-15

Applicant: REGENERON PHARMACEUTICALS, INC.

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

IPC: A01K67/027

CPC classification number: C07K16/00 ,  A01K67/0275 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C12N15/8509 ,  C12N2800/204 ,  C12P21/005

Abstract: Genetically modified non-human animals are provided that comprise an immunoglobulin heavy chain locus comprising an unrearranged human heavy chain variable region nucleotide sequence comprising an addition of at least one histidine codon or a substitution of at least one endogenous non-histidine codon with a histidine codon. Compositions and methods for making the genetically modified non-human animals as described herein are provided. Non-human animals capable of expressing an antigen-binding protein characterized by pH-dependent antigen binding, enhanced recyclability and/or enhanced serum half-life are also provided.

Abstract translation: 提供了包含免疫球蛋白重链基因座的转基因非人动物，其包含未经排列的人重链可变区核苷酸序列，其包含加入至少一个组氨酸密码子或至少一个内源性非组氨酸密码子与组氨酸密码子的取代 。 提供了制备如本文所述的转基因非人动物的组合物和方法。 还提供能够表达以pH依赖性抗原结合，增强的可回收性和/或增强的血清半衰期为特征的抗原结合蛋白的非人动物。