公开(公告)号：US20200061213A1

公开(公告)日：2020-02-27

申请号：US16530336

申请日：2019-08-02

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Lynn MACDONALD ,  Naxin Tu ,  Cagan Gurer ,  Sean Stevens ,  Andrew J. Murphy

IPC: A61K49/00 ,  A01K67/027 ,  C07K14/735 ,  G01N33/50

Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.

公开(公告)号：US20140013456A1

公开(公告)日：2014-01-09

申请号：US14030424

申请日：2013-09-18

Applicant: Regeneron Pharmaceuticals, Inc.

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

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

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.

Abstract translation: 提供了遗传修饰的非人动物，其中所述非人动物在免疫时表达能够与抗原结合的抗体。 提供了一种遗传修饰的非人动物，其表达源自在其种系序列中包含组氨酸修饰的人免疫球蛋白轻链可变基因区段的有限组分的人免疫球蛋白轻链可变结构域。 提供了将引入组氨酸密码子编码的组氨酸残基的非人动物表达为引入免疫球蛋白轻链核苷酸序列的方法。

公开(公告)号：US20130111616A1

公开(公告)日：2013-05-02

申请号：US13661116

申请日：2012-10-26

Applicant: REGENERON PHARMACEUTICALS, INC.

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

IPC: A01K67/027 ,  C12N15/873

CPC classification number: A01K67/0278 ,  A01K67/0271 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  C07K14/70539 ,  C12N15/8509

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β多肽）以及包含其的组织，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：US20240352111A1

公开(公告)日：2024-10-24

申请号：US18435815

申请日：2024-02-07

Applicant: Regeneron Pharmaceuticals, Inc.

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

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

CPC classification number: C07K16/22 ,  A61K39/3955 ,  A61P29/02 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/76 ,  C07K2317/92

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：US20240016129A1

公开(公告)日：2024-01-18

申请号：US18347009

申请日：2023-07-05

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Yajun Tang ,  Dan Chalothorn ,  Lyndon Mitnaul ,  Lori Morton ,  Daria Zamolodchikov ,  Nicole Alessandri-Haber ,  Lynn MACDONALD

IPC: A01K67/027 ,  C07K14/745 ,  C12N9/22 ,  C12N15/86 ,  C12Q1/6876

CPC classification number: A01K67/0278 ,  C07K14/745 ,  C12N9/22 ,  C12N15/86 ,  C12Q1/6876 ,  C12N2310/20 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/203

Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized coagulation factor XII (F12) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized F12 locus express a human coagulation factor XII protein or a chimeric coagulation factor XII protein, fragments of which are from human coagulation factor XII. Methods are provided for using such non-human animals comprising a humanized F12 locus to assess in vivo efficacy of human-coagulation-factor-XII-targeting reagents such as nuclease agents designed to target human F12. A short isoform of F12 that is produced locally in the brain, and methods of using the short isoform, are also provide.

公开(公告)号：US20180244804A1

公开(公告)日：2018-08-30

申请号：US15559358

申请日：2016-03-18

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Lynn MACDONALD ,  Andrew J. MURPHY ,  Cagan GURER ,  Robert BABB

IPC: C07K16/46 ,  C07K16/28 ,  A01K67/027

CPC classification number: C07K16/468 ,  A01K67/0278 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K16/00 ,  C07K16/28 ,  C07K16/462 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/51 ,  C07K2317/515 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/524 ,  C07K2317/526 ,  C07K2317/528 ,  C07K2317/53 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2317/92

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise an immunoglobulin heavy chain locus that includes unrearranged human immunoglobulin light chain gene segments and an immunoglobulin light chain locus that includes a single rearranged human light chain variable region nucleotide sequence. The unrearranged human light chain gene segments may be operably linked to a heavy chain constant region nucleotide sequence and the rearranged human immunoglobulin light chain variable region nucleotide sequence may be operably linked to a light chain constant region nucleotide 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 cognate variable domain, and expressing such nucleic acid sequences in a host cell, e.g., to generate a multispecific antigen-binding protein.

公开(公告)号：US20170260293A1

公开(公告)日：2017-09-14

申请号：US15601614

申请日：2017-05-22

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：US20160229906A1

公开(公告)日：2016-08-11

申请号：US15046105

申请日：2016-02-17

Applicant: Regeneron Pharmaceuticals, Inc.

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

IPC: C07K16/00 ,  C12N15/85 ,  C12P21/00 ,  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.

公开(公告)号：US20140245466A1

公开(公告)日：2014-08-28

申请号：US14185301

申请日：2014-02-20

Applicant: REGENERON PHARMACEUTICALS, INC.

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

IPC: A01K67/027

CPC classification number: A01K67/0278 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2267/03 ,  C07K14/70514 ,  C07K14/70517 ,  C07K14/70539 ,  C12N15/8509

Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human T cell co-receptor polypeptides (e.g., CD4, CD8α, CD8β), 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.

Abstract translation: 本发明提供表达嵌合人/非人T细胞共受体多肽（例如，CD4，CD8α，CD8和bgr）以及包含其的组织，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。

公开(公告)号：US20130198880A1

公开(公告)日：2013-08-01

申请号：US13798455

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

IPC: C07K16/46

CPC classification number: C07K16/462 ,  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 present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. 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.

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。 提供了提供两个人轻链可变基因片段的选择的小鼠，使得小鼠表达的免疫球蛋白轻链包含两个人轻链可变基因区段中的一个。 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。