公开(公告)号：US20240352489A1

公开(公告)日：2024-10-24

申请号：US18763490

申请日：2024-07-03

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Wojtek Auerbach ,  David Frendewey ,  Gustavo Droguett ,  Anthony Gagliardi ,  Junko Kuno ,  David M. Valenzuela

IPC: C12N15/90 ,  A01K67/0278 ,  C07K14/725 ,  C12N15/64

CPC classification number: C12N15/907 ,  A01K67/0278 ,  C07K14/7051 ,  C12N15/64 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0387 ,  C12N2810/00

Abstract: Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.

公开(公告)号：US20240352154A1

公开(公告)日：2024-10-24

申请号：US18607961

申请日：2024-03-18

Applicant: THE CHILDREN'S MEDICAL CENTER CORPORATION

Inventor： Frederick W. ALT ,  Suvi JAIN ,  Zhaoqing BA ,  Ming TIAN

IPC: C07K16/46 ,  A01K67/0278 ,  C12N5/0735 ,  C12N15/85

CPC classification number: C07K16/461 ,  A01K67/0278 ,  C12N5/0606 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2227/105 ,  C07K2317/10

Abstract: Described herein are compositions (e.g. cells and transgenic animals) and methods relating to engineered Ig loci that permit expression of particular antibodies or antibody segments while still permitting recombination and/or maturation process for antibody optimization.

公开(公告)号：US12116611B2

公开(公告)日：2024-10-15

申请号：US16965100

申请日：2019-01-27

Applicant: TECHNION RESEARCH & DEVELOPMENT FOUNDATION LIMITED

Inventor： Andrew Levy

IPC: C12Q1/02 ,  A01K67/0278 ,  A61K31/381 ,  A61P25/28 ,  C12N5/074

CPC classification number: C12Q1/025 ,  A01K67/0278 ,  A61K31/381 ,  A61P25/28 ,  C12N5/0696 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0356

Abstract: The invention provides a method of screening for a potential candidate for treating autism, epilepsy and/or intellectual disability in a subject in need comprising contacting a cell culture or an animal with the potential drug and detecting one or more of the following features: enhancing with the binding of apocalmodulin to the IQ domain of IQSEC2; reducing the production of ARF6-GTP; inhibiting the constitutive activation of guanine nucleotide exchange factor (GEF) IQSEC2; increasing the surface expression of AMPA receptors the brain or a cell; and/or increasing basal synaptic transmission in the brain or the cell. Further provided is a method of treating autism, epilepsy and/or intellectual disability in a subject in need by administering a drug capable of presenting one or more of the above identified features in the described cell and animal models.

公开(公告)号：US20240315221A1

公开(公告)日：2024-09-26

申请号：US18741870

申请日：2024-06-13

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Andrew J. MURPHY ,  Lynn MACDONALD ,  Cagan GURER ,  Karolina A. MEAGHER ,  Vera VORONINA ,  Brinda PRASAD

IPC: A01K67/0278 ,  A61K49/00 ,  C07K14/705 ,  C12N15/85

CPC classification number: A01K67/0278 ,  A61K49/0008 ,  C07K14/70596 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/03 ,  C12N2015/8527

Abstract: 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.

公开(公告)号：US12096754B2

公开(公告)日：2024-09-24

申请号：US17388111

申请日：2021-07-29

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Alexander O. Mujica ,  Elena Burova ,  Andrew J. Murphy

IPC: A01K67/0278 ,  A01K67/0276 ,  A61K49/00 ,  C07K14/705 ,  C07H21/04 ,  C12N15/63 ,  C12N15/79

CPC classification number: A01K67/0278 ,  A01K67/0276 ,  A61K49/0008 ,  C07K14/70503 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/03 ,  A01K2267/0331 ,  C07H21/04 ,  C12N15/63 ,  C12N15/79 ,  C12N2510/00 ,  C12N2517/02

Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

公开(公告)号：US12096753B2

公开(公告)日：2024-09-24

申请号：US17077545

申请日：2020-10-22

Applicant: Trianni, Inc.

Inventor： Matthias Wabl ,  Nigel Killeen

IPC: A01K67/0278 ,  A01K67/027 ,  C12N15/00 ,  C12N15/85 ,  C12P21/00

CPC classification number: A01K67/0278 ,  A01K67/027 ,  C12N15/00 ,  C12N15/8509 ,  C12P21/00 ,  A01K2217/07 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C12N2800/30

Abstract: The present invention comprises non-human vertebrate cells and non-human mammals having a genome comprising an introduced partially human immunoglobulin region, said introduced region comprising human VH coding sequences and non-coding VH sequences based on the endogenous genome of the non-human mammal.

公开(公告)号：US20240306617A1

公开(公告)日：2024-09-19

申请号：US18597797

申请日：2024-03-06

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Lynn Macdonald ,  Sean Stevens ,  Andrew J. Murphy ,  Margaret Karow

IPC: A01K67/0278 ,  A01K67/0275 ,  B60H1/32 ,  C07K16/22 ,  C07K16/28 ,  C07K16/40 ,  C07K16/46 ,  C12N9/64 ,  C12N15/85

CPC classification number: A01K67/0278 ,  A01K67/0275 ,  B60H1/32281 ,  C07K16/22 ,  C07K16/28 ,  C07K16/2866 ,  C07K16/40 ,  C07K16/461 ,  C07K16/462 ,  C12N9/6489 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/01 ,  C07K2317/21 ,  C07K2317/92 ,  C12N2800/204 ,  C12N2800/30

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

公开(公告)号：US12082566B2

公开(公告)日：2024-09-10

申请号：US17490449

申请日：2021-09-30

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Andrew J. Murphy ,  Lynn MacDonald ,  Cagan Gurer ,  Karolina A. Meagher ,  Vera Voronina ,  Brinda Prasad

IPC: A01K67/0278 ,  A61K49/00 ,  C07K14/705 ,  C12N15/85

CPC classification number: A01K67/0278 ,  A61K49/0008 ,  C07K14/70596 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/052 ,  A01K2227/105 ,  A01K2267/03 ,  C12N2015/8527

Abstract: 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.

公开(公告)号：US20240288445A1

公开(公告)日：2024-08-29

申请号：US18603889

申请日：2024-03-13

Applicant: The Jackson Laboratory

Inventor： James Keck ,  Chunting Ye

IPC: G01N33/68 ,  A01K67/0278 ,  C07K16/28

CPC classification number: G01N33/6863 ,  A01K67/0278 ,  C07K16/2809 ,  C07K16/2818 ,  C07K16/2887 ,  C07K16/2893 ,  A01K2227/105 ,  A01K2267/0325

Abstract: Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.

公开(公告)号：US12060571B2

公开(公告)日：2024-08-13

申请号：US16369565

申请日：2019-03-29

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Wojtek Auerbach ,  David Frendewey ,  Gustavo Droguett ,  Anthony Gagliardi ,  Junko Kuno ,  David M. Valenzuela

IPC: A01K67/0278 ,  C07K14/725 ,  C12N15/64 ,  C12N15/90

CPC classification number: C12N15/907 ,  A01K67/0278 ,  C07K14/7051 ,  C12N15/64 ,  A01K2207/15 ,  A01K2217/072 ,  A01K2217/15 ,  A01K2227/105 ,  A01K2267/0387 ,  C12N2810/00

Abstract: Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.