公开(公告)号：US20240229048A1

公开(公告)日：2024-07-11

申请号：US18441490

申请日：2024-02-14

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Chris Schoenherr ,  John McWhirter ,  Corey Momont ,  Caitlin L. Goshert ,  Lynn Macdonald ,  Gregg S. Warshaw ,  Jose F. Rojas ,  Ka-Man Venus Lai ,  David M. Valenzuela ,  Andrew J. Murphy

IPC: C12N15/66 ,  C12N15/10 ,  C12N15/64

CPC classification number: C12N15/66 ,  C12N15/1031 ,  C12N15/64

Abstract: Methods are provided herein for assembling at least two nucleic acids using a sequence specific nuclease agent (e.g., a gRNA-Cas complex) to create end sequences having complementarity and subsequently assembling the overlapping complementary sequences. The nuclease agent (e.g., a gRNA-Cas complex) can create double strand breaks in dsDNA in order to create overlapping end sequences or can create nicks on each strand to produce complementary overhanging end sequences. Assembly using the method described herein can assemble any nucleic acids having overlapping sequences or can use a joiner oligo to assemble sequences without complementary ends.

公开(公告)号：US11937587B2

公开(公告)日：2024-03-26

申请号：US17118241

申请日：2020-12-10

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Kara L. Olson ,  Eric Smith ,  Ka-Man Venus Lai ,  Andrew J. Murphy ,  Gavin Thurston ,  Dayong Guo

IPC: A01K67/027 ,  C07K14/725 ,  C12N5/071 ,  C12N15/85 ,  G01N33/50

CPC classification number: A01K67/0278 ,  A01K67/0276 ,  C07K14/7051 ,  C12N5/0602 ,  C12N15/8509 ,  G01N33/5088 ,  A01K2207/12 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/03 ,  A01K2267/0337 ,  Y02A50/30

Abstract: Non-human animals, expressing humanized CD3 proteins are provided. Non-human animals, e.g., rodents, genetically modified to comprise in their genome humanized CD3 proteins are also provided. Additionally, provided are methods and compositions of making such non-human animals, as well as methods of using said non-human animals.

公开(公告)号：US11730150B2

公开(公告)日：2023-08-22

申请号：US16717597

申请日：2019-12-17

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Charleen Hunt ,  Jason Mastaitis ,  Guochun Gong ,  Ka-Man Venus Lai ,  Jesper Gromada ,  Aris N. Economides

IPC: A01K67/027 ,  A61K49/00 ,  C07K14/78

CPC classification number: A01K67/0275 ,  A61K49/0008 ,  C07K14/78 ,  A01K2217/00 ,  A01K2217/056 ,  A01K2227/105 ,  A01K2267/0306

Abstract: Provided are non-human animals comprising a mutation in the Fbn1 gene to model neonatal progeroid syndrome with congenital lipodystrophy (NPSCL). Also provided are methods of making such non-human animal models. The non-human animal models can be used for screening compounds for activity in inhibiting or reducing NPSCL or ameliorating NPSCL-like symptoms or screening compounds for activity potentially harmful in promoting or exacerbating NPSCL as well as to provide insights in to the mechanism of NPSCL and potentially new therapeutic and diagnostic targets.

公开(公告)号：US20230189771A1

公开(公告)日：2023-06-22

申请号：US18056118

申请日：2022-11-16

Applicant: Regeneron Pharmaceuticals, Inc. ,  President and Fellows of Harvard College

Inventor： Ka-Man Venus Lai ,  Guochun Gong ,  John Rinn ,  David Frendewey ,  David M. Valenzuela

IPC: A01K67/027 ,  A61D19/04 ,  C12Q1/6876

CPC classification number: A01K67/0276 ,  A61D19/04 ,  C12Q1/6876 ,  A01K2217/075 ,  A01K2217/077 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0393 ,  C12Q2600/158 ,  C12Q2600/178

Abstract: Genetically modified non-human animals are provided that exhibit a functional lack of one or more IncRNAs. Methods and compositions for disrupting, deleting, and/or replacing IncRNA-encoding sequences are provided. Genetically modified mice that age prematurely are provided. Also provided are cells, tissues and embryos that are genetically modified to comprise a loss-of-function of one or more IncRNAs.

公开(公告)号：US11503813B2

公开(公告)日：2022-11-22

申请号：US16732400

申请日：2020-01-02

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Jose F. Rojas ,  Ka-Man Venus Lai ,  Andrew J. Murphy ,  Cagan Gurer

IPC: A01K67/027 ,  C12N15/85 ,  C07K14/54

Abstract: Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

公开(公告)号：US11470828B2

公开(公告)日：2022-10-18

申请号：US16744493

申请日：2020-01-16

Applicant: REGENERON PHARMACEUTICALS, INC.

Inventor： Meghan Drummond Samuelson ,  Brian Zambrowicz ,  Ka-Man Venus Lai ,  Charleen Hunt ,  Susannah Brydges ,  Andrew J. Murphy ,  Claudia Gonzaga-Jauregui ,  Jose Rojas ,  Nicole Alessandri-Haber ,  Robert Breese ,  Susan D. Croll

IPC: A01K67/027 ,  C12N15/85 ,  C07K14/72

Abstract: This disclosure relates to an animal model of human disease. More specifically, this disclosure relates to a rodent model of mood disorders such as unipolar depression and an anxiety disorder. Disclosed herein are genetically modified rodent animals that carry a humanized G protein-coupled receptor 156 (GPR156) gene that encodes a mutant human GPR156 protein comprising Asp at an amino acid position corresponding to position 533 in a full length wild type human GPR156 protein.

公开(公告)号：US20210301301A1

公开(公告)日：2021-09-30

申请号：US17196408

申请日：2021-03-09

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Jeffrey D. Lee ,  Alexander O. Mujica ,  Wojtek Auerbach ,  Ka-Man Venus Lai ,  David M. Valenzuela ,  George D. Yancopoulos

IPC: C12N15/85 ,  A61D19/04 ,  A01K67/027 ,  C07K14/715 ,  C07K14/775 ,  C12N15/90

Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

公开(公告)号：US10975390B2

公开(公告)日：2021-04-13

申请号：US16451859

申请日：2019-06-25

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Jeffrey D. Lee ,  Alexander O. Mujica ,  Wojtek Auerbach ,  Ka-Man Venus Lai ,  David M. Valenzuela ,  George D. Yancopoulos

IPC: C12N15/85 ,  A61D19/04 ,  A01K67/027 ,  C07K14/715 ,  C07K14/775 ,  C12N15/90

Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

公开(公告)号：US20200370054A1

公开(公告)日：2020-11-26

申请号：US16986077

申请日：2020-08-05

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： David Heslin ,  Roxanne Ally ,  Chia-Jen Siao ,  Ka-Man Venus Lai ,  David M. Valenzuela ,  Chunguang Guo ,  Michael LaCroix-Fralish ,  Lynn Macdonald ,  Aarti Sharma-Kanning ,  Daisuke Kajimura ,  Gustavo Droguett ,  David Frendewey ,  Alexander O. Mujica

IPC: C12N15/62 ,  A01K67/027 ,  C12N15/113 ,  C12N15/90 ,  C12N5/0793 ,  C12N5/0797

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.

公开(公告)号：US20200291425A1

公开(公告)日：2020-09-17

申请号：US16891978

申请日：2020-06-03

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： David Frendewey ,  Wojtek Auerbach ,  Ka-Man Venus Lai ,  David M. Valenzuela ,  George D. Yancopoulos

IPC: C12N15/85 ,  C12N15/90 ,  C12N9/22 ,  A01K67/027 ,  C12N15/10

Abstract: Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.