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公开(公告)号：US11697685B2
公开(公告)日：2023-07-11
申请号：US16700401
申请日：2019-12-02
发明人： Huashun Li , Baolei Wang , Kunkun Han
IPC分类号： C07K16/28 , C07K14/705 , C12N5/0783 , A61K35/17 , A61P35/00 , C07K14/725 , C12N15/867 , A61K38/00 , A61K39/00
CPC分类号： C07K16/2803 , A61K35/17 , A61P35/00 , C07K14/7051 , C07K14/70517 , C07K14/70521 , C07K14/70578 , C12N5/0646 , C12N15/867 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/622 , C07K2317/76 , C07K2319/02 , C07K2319/03 , C07K2319/30 , C07K2319/33 , C12N5/0636 , C12N2510/00
摘要： The present invention relates to chimeric antigen receptor cells targeting ROBO1, in particular, enhanced CAR-T cells and CAR-NK cells targeting ROBO1, and preparation and application thereof. The cells can stably expressing CAR elements, while secreting extracellular domain molecules expressing PD-1 protein or mutants thereof, and thus may block PD-11PD-L1 molecular interaction. It has been found through animal experiments that the cells have very good anti-tumor effects, and the above-mentioned cells can significantly reduce tumor recurrence and improve the survival rate compared with the conventional ROBO1-targeted CAR modified cells.
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公开(公告)号：US11149071B2
公开(公告)日：2021-10-19
申请号：US16691186
申请日：2019-11-21
发明人： Huashun Li , Baoyong Ren , Peng Liu
IPC分类号： A61K38/00 , C07K14/47 , A61P11/06 , A61P29/00 , C07K14/765
摘要： The present invention provides a recombinant fusion protein. The fusion protein is formed by the fusion of D2 domain of Slit2 protein and HSA protein, and the position 386 amino acid of the Slit2 protein molecule is serine.
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公开(公告)号：US20190309050A1
公开(公告)日：2019-10-10
申请号：US16430984
申请日：2019-06-04
发明人： Huashun Li , Baoyong Ren , Peng Liu
IPC分类号： C07K14/765 , A61K38/17 , C12N15/85 , C12N15/62 , A61K9/00 , A61K9/08 , C07K14/47 , A61P9/00 , A61P11/16
摘要： The present invention relates to the field of biomedical technology, in particular to a fusion protein Slit2D2(C386S)-HSA and use thereof in the treatment and/or prevention of fibrotic diseases. In the fusion protein, the amino acid residue is mutated on the basis of the Slit2D2 domain, which improves the stability of the fusion protein compared with the native protein. The above fusion protein is obtained by fusing Slit2D2(C386S) with HSA protein, which prolongs the metabolism time of the drug while improving the stability of the drug. The fusion protein provided by the present invention is more effective than the positive control drug in the prevention and treatment of fibrotic diseases, particularly pulmonary fibrosis, and shows good drug-forming properties.
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公开(公告)号：US11738051B2
公开(公告)日：2023-08-29
申请号：US16893989
申请日：2020-06-05
发明人： Huashun Li , Kunkun Han , Baolei Wang , Baoyong Ren
IPC分类号： A61K35/17 , A61P35/00 , C07K14/725 , C07K14/705 , C12N15/62
CPC分类号： A61K35/17 , A61P35/00 , C07K14/7051 , C07K14/70517 , C07K14/70578 , C12N15/62
摘要： The present invention provides a nucleotide sequence for encoding CAR, a ROBO1 CAR-NK cell of expressing the CAR, and preparation and application thereof. The ROBO1 CAR-NK cell provided by the present invention can specifically kill tumor cells by using ROBO1 antibody for the construction of CAR-NK cells and using ROBO1 molecules as target antigens. It can be used as a therapeutic agent for tumor diseases, for the treatment of tumor with highly expressing of ROBO1, without harmful phenomena such as cytokine release syndrome, thus providing new treatments for the tumors which are ineffective in traditional surgery, chemotherapy and radiotherapy. It has lower toxicity, higher safety and better specific lysis activity compared with ROBO1 CAR-T cell.
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公开(公告)号：US11680106B2
公开(公告)日：2023-06-20
申请号：US17711121
申请日：2022-04-01
发明人： Huashun Li , Baoyong Ren
CPC分类号： C07K16/3015 , A61P35/00 , C07K16/2809 , C07K16/3023 , C07K2317/31 , C07K2317/56 , C12N15/63
摘要： Disclosed are a bispecific antigen-binding construct and the preparation method and use thereof, wherein the construct comprises a first antigen binding unit and a second antigen binding unit, the first antigen binding unit is a single chain variable region antibody fragment ScFV which specifically binds to the surface antigen of immune cells, and the second antigen binding unit is a Slit2D2 protein fragment which specifically binds to the surface antigen Robo1 of tumour cells. That is to say, the construct can bind to the surface antigen of immune cells and the surface Robo1 molecule of tumour cells at the same time, so that as the distance between tumour cells and immune cells get smaller, the quiescent immune cells are effectively activated, and the effect of killing and wounding tumours is produced. The construct has advantages of small molecular weight and good tissue penetrability, has significant killing and wounding effects on the tumour cells which express a large amount of Robo1, and can be used in the development of anti-tumour drugs.
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公开(公告)号：US11345893B2
公开(公告)日：2022-05-31
申请号：US16094247
申请日：2016-07-31
发明人： Huashun Li
IPC分类号： C07K14/705 , C12N5/0786 , A61P35/00 , C12N15/85 , C12N5/0783 , C12N15/62 , A61K38/17 , C12N5/10
摘要： Provided is a method for modifying a chimeric antigen receptor-modified T cell (CAR-T cell). The method comprises expressing an SCFV-CDS TM-4-1BB-CD3ζ molecule in a T cell. The CAR-T cell prepared using the method can specifically recognize and bind to a tumor cell with elevated expression of a ROBO1 protein, and can be used to prevent and treat a corresponding tumor-related disease.
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公开(公告)号：US11339225B2
公开(公告)日：2022-05-24
申请号：US16300650
申请日：2017-05-11
发明人： Huashun Li , Baoyong Ren
摘要： Disclosed are a bispecific antigen-binding construct and the preparation method and use thereof, wherein the construct comprises a first antigen binding unit and a second antigen binding unit, the first antigen binding unit is a single chain variable region antibody fragment ScFV which specifically binds to the surface antigen of immune cells, and the second antigen binding unit is a Slit2D2 protein fragment which specifically binds to the surface antigen Robo1 of tumour cells. That is to say, the construct can bind to the surface antigen of immune cells and the surface Robo1 molecule of tumour cells at the same time, so that as the distance between tumour cells and immune cells get smaller, the quiescent immune cells are effectively activated, and the effect of killing and wounding tumours is produced. The construct has advantages of small molecular weight and good tissue penetrability, has significant killing and wounding effects on the tumour cells which express a large amount of Robo1, and can be used in the development of anti-tumour drugs.
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公开(公告)号：US11331345B2
公开(公告)日：2022-05-17
申请号：US16389954
申请日：2019-04-21
发明人： Huashun Li , Baolei Wang , Kunkun Han , Baoyong Ren
IPC分类号： A61K35/17 , C07K14/47 , A61P35/00 , C12N15/86 , A61K48/00 , C12N15/62 , C12N15/867 , C12N5/10 , C07K19/00
摘要： Provided are a PD-1 CAR NK-92 cell and a preparation method and use thereof. The PD-1 CAR NK-92 cell expresses PD-1-CD8™-4-1BB-CD3ζ fusion protein in NK-92 cells. The PD-1 CAR NK-92 is obtained by infecting an NK92 cell line with a PD-1 CAR molecule and obtaining monoclonal cells by means of flow screening, and culturing and expanding CAR NK92 monoclonal cell strains with stable traits and a high killing activity. The cells can be produced on a large scale, can be used in different patients without GVHR rejection, and have a specific killing activity and significant therapeutic effect on tumors.
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公开(公告)号：US11246888B2
公开(公告)日：2022-02-15
申请号：US16160735
申请日：2018-10-15
发明人： Huashun Li , Baolei Wang , Baoyong Ren
IPC分类号： A61K35/17 , C07K14/705 , C07K19/00 , C12N15/09 , A61P35/00 , C07K14/725 , C12N15/85 , C12N5/10 , C07K14/78 , C07K14/73
摘要： A chimeric antigen receptor (CAR) and a gene encoding the CAR. The CAR comprises an extracellular domain capable of binding to an antigen, a transmembrane domain, and intracellular immune co-stimulatory molecule, wherein the extracellular domain comprises a D2 domain of a Slit2 protein. A chimeric antibody-expressing cell, which introduces a gene encoding the CAR into a cell so as to express the CAR on the surface of the cell. The CAR or CAR-expressing cell can be used as a cell drug for the treatment of tumor diseases. By using the CAR for engineering cells, especially T cells, the engineered T cells can specifically recognize and kill tumors, and have higher tumoricidal activity.
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