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1.
公开(公告)号:US20190208753A1
公开(公告)日:2019-07-11
申请号:US16353870
申请日:2019-03-14
申请人: Kymab Limited
发明人: Jasper Clube
IPC分类号: A01K67/027 , C07K16/46 , C12N15/85 , C07K16/00
CPC分类号: A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2217/15 , A01K2227/105 , A01K2267/01 , C07K16/00 , C07K16/461 , C07K16/462 , C07K2317/92 , C12N15/8509
摘要: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.
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2.
公开(公告)号:US20180264038A1
公开(公告)日:2018-09-20
申请号:US15764187
申请日:2016-09-28
CPC分类号: A61K35/17 , A01K2207/15 , A01K2227/105 , A01K2267/0387 , A61K9/0019 , A61K48/005 , A61P37/06 , C07K16/2803 , C07K2317/622 , C07K2319/03 , C07K2319/33 , C12N2740/10043
摘要: Provided herein are methods and materials for treating autoimmune diseases and alloimmune diseases. Specifically, provided are a pharmaceutical composition comprising a therapeutically effective amount of a population of modified human T cells, wherein the human T cells are modified to comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR) construct, wherein the CAR construct comprises an antigen binding domain, wherein the antigen binding domain is specific for a ligand expressed on B cells, plasma cells or plasmablasts in human patients suffering from an autoimmune disease or an alloimmune disease; and a method of treating an autoimmune or an alloimmune disease in a human patient, the method comprising: administering a pharmaceutical composition.
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公开(公告)号:US10070632B2
公开(公告)日:2018-09-11
申请号:US15442857
申请日:2017-02-27
发明人: Lisa Purcell , Alexander O. Mujica , Yajun Tang
IPC分类号: A01K67/027 , C12N5/0735 , C12N9/64
CPC分类号: A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/072 , A01K2227/10 , A01K2227/105 , A01K2267/0337 , A61K48/00 , C07K14/47 , C07K2319/00 , C12N5/0606 , C12N9/6424 , C12N15/09 , C12N15/63 , C12N15/86 , C12N2710/10332
摘要: Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.
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公开(公告)号:US20180213755A1
公开(公告)日:2018-08-02
申请号:US15575988
申请日:2016-04-20
发明人: Mamoru ITO , Ikumi KATANO
IPC分类号: A01K67/027 , C12N15/85
CPC分类号: A01K67/0278 , A01K2207/12 , A01K2207/15 , A01K2217/052 , A01K2227/105 , A01K2267/01 , A01K2267/03 , C07K14/5443 , C12N15/8509 , C12N2015/8518
摘要: An object of the present invention is to provide a mouse that enables the functions of human NK cell to be studied. A DNA consisting of a nucleotide sequence represented by SEQ ID NO: 1, which is a gene region comprising a DNA in which a cDNA sequence encoding interleukin 15 (IL-15) is operably ligated to a cDNA sequence encoding the signal peptide of human interleukin (IL-2), is inserted to immunodeficient mouse cDNA. In NOD-scid, IL-2rγnull-hIL-15 Tg mice thus generated, hCD56+ cell having a concentration sufficient for conducting in vivo study on human mature NK cell are detected for at least 6 months after transplantation.
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公开(公告)号:US20180186876A1
公开(公告)日:2018-07-05
申请号:US15897400
申请日:2018-02-15
IPC分类号: C07K16/28 , A01K67/027 , C07K16/30 , A61K39/395 , A61K45/06 , A61K39/00
CPC分类号: C07K16/28 , A01K67/0275 , A01K2207/15 , A01K2217/072 , A01K2227/105 , A61K39/39558 , A61K45/06 , A61K2039/505 , C07K16/2896 , C07K16/3061 , C07K2317/24 , C07K2317/72 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/92
摘要: Chimeric and humanized anti-CD37 antibodies and pharmaceutical compositions containing them are useful for the treatment of B cell malignancies and autoimmune and inflammatory diseases that involve B cells in their pathology.
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6.
公开(公告)号:US20180184629A1
公开(公告)日:2018-07-05
申请号:US15736951
申请日:2016-06-16
IPC分类号: A01K67/027 , A61K49/00 , C12N15/90
CPC分类号: A01K67/0275 , A01K67/027 , A01K67/0271 , A01K2207/12 , A01K2207/15 , A01K2217/07 , A01K2227/105 , A01K2267/0387 , A61K49/0008 , C07K14/472 , C12N15/907
摘要: The present invention relates generally to genetically modified non-human animals and immunodeficient non-human animals characterized by restored complement-dependent cytotoxicity, as well as methods and compositions for assessment of therapeutic antibodies in the genetically modified immunodeficient non-human animals. In specific aspects, the present invention relates to immunodeficient non-obese diabetic (NOD), A/J, A/He, AKR, DBA/2, NZB/BIN, B10.D2/oSn and other mouse strains genetically modified to restore complement-dependent cytotoxicity which is lacking in the unmodified immunodeficient mice. In further specific aspects, the present invention relates to NOD.Cg-Prkdcscid IL2rgtm1Wj1/SzJ (NSG), NOD. Cg-Rag1tm1Mom IL2rgtm1Wj1/SzJ (NRG) and NOD.Cg-Prkdcscid IL2rgtm1Wj1/JicTAc (NOG) mice genetically modified to restore complement-dependent cytotoxicity which is lacking in unmodified NSG, NRG and NOG mice. Methods for assessment of therapeutic antibodies or putative therapeutic antibodies in the genetically modified immunodeficient mice characterized by an intact complement system are provided according to specific aspects of the present invention.
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7.
公开(公告)号:US20180171324A1
公开(公告)日:2018-06-21
申请号:US15887083
申请日:2018-02-02
申请人: FUJIFILM Corporation
IPC分类号: C12N11/02 , A01K67/027 , C12N5/095 , A61K49/00
CPC分类号: C12N11/02 , A01K67/0271 , A01K2207/12 , A01K2207/15 , A01K2207/30 , A01K2227/105 , A01K2267/0331 , A61K35/13 , A61K35/28 , A61K49/0008 , A61L27/00 , C12N5/0695 , C12N2533/54 , G01N33/50
摘要: An object of the present invention is to provide a non-human model animal rich in stromal tissue, a cell structure useful for producing the above-described non-human model animal, a method for evaluating a test substance in which the above-described non-human model animal is used, and a method for producing the above-described non-human model animal. According to the present invention, a cell structure is provided which contains a biocompatible macromolecular block and at least a cancer cell and a mesenchymal cell, and in which a plurality of the above-described biocompatible macromolecular blocks are arranged in gaps between a plurality of the above-described cells.
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公开(公告)号:US20180160662A1
公开(公告)日:2018-06-14
申请号:US15880513
申请日:2018-01-25
申请人: Institut Pasteur
IPC分类号: A01K67/027 , C07K14/705 , C12N15/85 , G01N33/50 , C07K14/74
CPC分类号: A01K67/0278 , A01K67/0271 , A01K2207/12 , A01K2207/15 , A01K2217/052 , A01K2217/15 , A01K2217/206 , A01K2227/105 , A01K2267/03 , A01K2267/0331 , A01K2267/0337 , A01K2267/0381 , C07K14/70503 , C07K14/70539 , C07K14/70596 , C12N15/8509 , C12N2800/107 , G01N33/5088 , G01N2500/10
摘要: The present invention provides a transgenic mouse which comprises a deficiency for murine T lymphocytes, B lymphocytes and NK cells, a deficiency for murine MHC class I and MHC class II molecules, and a functional xenogenic SIRPα transgene. This mouse is useful for in vivo screening of various compounds, including immuno-therapeutic agents and vaccines. The said mouse is also useful for testing the in vivo metabolism of xenobiotic compounds.
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公开(公告)号:US20180146650A1
公开(公告)日:2018-05-31
申请号:US15823036
申请日:2017-11-27
申请人: LISA PORTER , BRE-ANNE FIFIELD , DOROTA LUBANSKA
发明人: LISA PORTER , BRE-ANNE FIFIELD , DOROTA LUBANSKA
IPC分类号: A01K67/027 , A61K49/00
CPC分类号: A01K67/0278 , A01K67/0275 , A01K2207/15 , A01K2217/052 , A01K2217/072 , A01K2227/105 , A01K2267/0331 , A61K49/0008 , C07K14/005 , C12N2740/12022
摘要: In one aspect, the invention provides a transgenic non-human animal model having germ cells and somatic cells containing an endogenous MMTV-SV40-Spy1A gene sequence introduced into said animal model or an ancestor of said animal model at an embryonic stage, wherein said gene sequence comprises a mouse mammary tumor virus gene (MMTV), a functionally disrupted SV40 gene (SV40) and a human Spy1A gene. In another aspect, the present invention provides a transgenic non-human animal model whose germ cells and somatic cells contain an endogenous Spy1A-pTRE-Tight gene sequence introduced into said animal model or an ancestor of said animal model at an embryonic stage. Preferably, the Spy1A-pTRE-Tight animal model expresses the Spy1A gene and develop cancer, preferably breast cancer, when administered with tetracycline, preferably doxycycline.
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公开(公告)号:US09982062B2
公开(公告)日:2018-05-29
申请号:US15177280
申请日:2016-06-08
发明人: William Don Harriman
IPC分类号: A01N63/00 , C07K16/46 , A01K67/027 , C07K16/00
CPC分类号: C07K16/462 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/05 , A01K2217/052 , A01K2227/101 , A01K2227/102 , A01K2227/103 , A01K2227/107 , A01K2227/30 , A01K2267/01 , C07K16/005 , C07K16/468 , C07K2317/14 , C07K2317/23 , C07K2317/24 , C07K2317/31 , C07K2317/52 , C07K2317/56 , C07K2317/569 , C07K2317/622 , C07K2317/64
摘要: A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.
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