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公开(公告)号：US20240327785A1
公开(公告)日：2024-10-03
申请号：US18543857
申请日：2023-12-18
IPC分类号： C12N5/0735 , A01K67/0275 , A01K67/0278 , C07K16/00 , C07K16/18 , C07K16/46 , C12N15/10 , C12N15/85
CPC分类号： C12N5/0606 , A01K67/0275 , A01K67/0278 , C07K16/00 , C07K16/18 , C07K16/461 , C07K16/462 , C12N15/10 , C12N15/8509 , A01K2207/15 , A01K2217/05 , A01K2217/052 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , A01K2267/02 , A01K2267/0381 , C07K2317/10 , C07K2317/14 , C07K2317/21 , C07K2317/24 , C07K2317/50 , C07K2317/515 , C07K2317/56 , C07K2317/64
摘要： Genetically modified mice are provided that express human λ variable (hVλ) sequences, including mice that express hVλ sequences from an endogenous mouse λ light chain locus, mice that express hVλ sequences from an endogenous mouse κ light chain locus, and mice that express hVλ sequences from a transgene or an episome wherein the hVλ sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human λ variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human λ variable sequences, including human antibodies, are provided.
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公开(公告)号：US11963521B2
公开(公告)日：2024-04-23
申请号：US17394492
申请日：2021-08-05
发明人： Li-Hsien Wang , Yingzi Xue , Andrew J. Murphy , Sean Stevens
IPC分类号： G01N33/00 , A01K67/0278 , C07K14/54 , C07K14/715
CPC分类号： A01K67/0278 , C07K14/5406 , C07K14/7155 , A01K2207/15 , A01K2217/072 , A01K2217/20 , A01K2227/105 , A01K2267/01 , A01K2267/0368 , A01K2267/0393
摘要： Non-human animals comprising a human or humanized IL-4 and/or IL-4Rα nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous IL-4 gene and/or IL-4Rα gene with a human IL-4 gene and/or IL-4Rα gene in whole or in part, and methods for making and using the non-human animals, are described. Non-human animals comprising a human or humanized IL-4 gene under control of non-human IL-4 regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4-encoding sequence with human IL-4-encoding sequence at an endogenous non-human IL-4 locus. Non-human animals comprising a human or humanized IL-4Rα gene under control of non-human IL-4Rα regulatory elements is also provided, including non-human animals that have a replacement of non-human IL-4Rα-encoding sequence with human or humanized IL-4Rα-encoding sequence at an endogenous non-human C IL-4Rα locus. Non-human animals comprising human or humanized IL-4 gene and/or IL-4Rα sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided.
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公开(公告)号：US11950578B2
公开(公告)日：2024-04-09
申请号：US17129708
申请日：2020-12-21
发明人： Lynn Macdonald , Sean Stevens , Andrew J. Murphy , Margaret Karow
IPC分类号： C07K16/00 , A01K67/0275 , A01K67/0278 , B60H1/32 , C07K16/22 , C07K16/28 , C07K16/40 , C07K16/46 , C12N9/64 , C12N15/85
CPC分类号： 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
摘要： 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.
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公开(公告)号：US20240099278A1
公开(公告)日：2024-03-28
申请号：US18236218
申请日：2023-08-21
申请人： Regeneron Pharmaceuticals, Inc. , Yale University , Institute for Research In Biomedicine (IRB)
发明人： Richard Flavell , Till Strowig , Markus G. Manz , Chiara Borsotti , Madhav Dhodapkar , Andrew J. Murphy , Sean Stevens , George D. Yancopoulos
IPC分类号： A01K67/027
CPC分类号： A01K67/0278 , A01K67/0276 , C07K14/535
摘要： Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.
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公开(公告)号：US11766032B2
公开(公告)日：2023-09-26
申请号：US16672042
申请日：2019-11-01
申请人： Regeneron Pharmaceuticals, Inc. , Yale University , Institute for Research in Biomedicine (IRB)
IPC分类号： A01K67/00 , A01K67/027 , C07H21/04 , C12N9/14 , C07K14/54 , C07K14/475 , C12Q1/18 , C07K14/505 , C12N9/00 , C07K14/535 , C07K14/47 , G01N33/50 , C07K14/715 , A61K49/00 , C07K14/52
CPC分类号： A01K67/0271 , A01K67/0276 , A01K67/0278 , A61K49/0008 , C07K14/4703 , C07K14/475 , C07K14/505 , C07K14/524 , C07K14/535 , C07K14/5403 , C07K14/5437 , C07K14/7155 , C12N9/00 , C12N9/14 , C12Q1/18 , G01N33/5088 , A01K2207/12 , A01K2207/15 , A01K2217/05 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/01 , A01K2267/0337 , A01K2267/0381 , C12Y301/03048
摘要： Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.
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公开(公告)号：US11666040B2
公开(公告)日：2023-06-06
申请号：US16849782
申请日：2020-04-15
IPC分类号： A01K67/027 , C12P21/02 , C07K16/46
CPC分类号： A01K67/0278 , A01K67/0276 , C07K16/461 , C12P21/02 , A01K2207/15 , A01K2217/072 , A01K2217/075 , A01K2217/15 , A01K2227/105
摘要： Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.
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公开(公告)号：US20230094591A1
公开(公告)日：2023-03-30
申请号：US17749728
申请日：2022-05-20
发明人： Sean Stevens , Tammy T. Huang , Joel H. Martin , Jeanette L. Fairhurst , Ashique Rafique , Eric Smith , Kevin J. Pobursky , Nicholas J. Papadopoulos , James P. Fandl , Gang Chen , Margaret Karow
摘要： A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a KD of about 500 pM or less and blocks IL-6 activity with an IC50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.
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公开(公告)号：US20220394959A1
公开(公告)日：2022-12-15
申请号：US17734392
申请日：2022-05-02
IPC分类号： A01K67/027 , C07K16/00 , C12N9/64 , C12N15/85
摘要： Mice, tissues, cells, and genetic material are provided that comprise a humanized heavy chain immunoglobulin locus, a humanized light chain locus that expresses a universal light chain, and a gene encoding an ADAM6 or ortholog or homolog or functional fragment thereof. Mice are provided that express humanized heavy chains comprising human variable domains, and that express humanized light chains comprising human variable domains wherein the light chains are derived from no more than one, or no more than two, light chain V and J or rearranged V/J sequences. Fertile male mice that express antibodies with universal light chains and humanized heavy chains are provided. Methods and compositions for making bispecific binding proteins are provided.
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公开(公告)号：US20220053742A1
公开(公告)日：2022-02-24
申请号：US17385039
申请日：2021-07-26
IPC分类号： A01K67/027 , C07K14/54 , C07K14/715 , C12N5/0735 , C12N5/10 , C12N5/16 , C12N15/90
摘要： Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6Rα locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.
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公开(公告)号：US20220000084A1
公开(公告)日：2022-01-06
申请号：US17343294
申请日：2021-06-09
申请人： Regeneron Pharmaceuticals, Inc. , Yale University , Institute for Research in Biomedicine (IRB)
发明人： Sean Stevens , Andrew J. Murphy , Richard Flavell , Elizabeth Eynon , Jorge Galan , Tim Willinger , Markus Manz , Anthony Rongvaux , George D. Yancopoulos
IPC分类号： A01K67/027 , C07K14/52 , C07K14/535 , C07K14/54 , C07K14/715 , C12N9/00 , A61K49/00
摘要： A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.
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