公开(公告)号：US20240415976A1

公开(公告)日：2024-12-19

申请号：US18698795

申请日：2022-10-10

Applicant: RENEURON LIMITED

Inventor： Paul HOLE ,  Ruben DEOGRACIAS ,  Randolph CORTELING

IPC: A61K47/69 ,  A61K35/22 ,  A61K38/18 ,  C07K14/475 ,  C07K14/705

Abstract: The present invention provides proteins that are linked to glycosylphosphatidylinositol (GPI). The invention provides a fusion protein comprising a protein of interest and a carboxy-terminal glycosylphosphatidylinositol (GPI) anchor peptide sequence. Proteins of interest include neurotrophins such as BDNF. The invention also provides a fusion protein comprising a protein of interest, a linker peptide and a final carboxy-terminal residue, wherein the final carboxy-terminal residue is covalently linked to glycosylphosphatidylinositol (GPI). The GPI may be anchored to the membrane of an extracellular vesicle. Methods of making and using the fusion proteins and extracellular vesicles of the invention are also provided, including their use in therapy.

公开(公告)号：US20150164955A1

公开(公告)日：2015-06-18

申请号：US14414670

申请日：2013-07-18

Applicant: RENEURON LIMITED

Inventor： John Sinden ,  Lara Stevanato ,  Randolph Corteling

IPC: A61K35/30 ,  C12N5/0797 ,  A61K9/16

CPC classification number: A61K35/30 ,  A61K9/1664 ,  A61K31/7105 ,  A61K31/713 ,  C12N5/0623 ,  C12N2501/15 ,  C12N2501/24 ,  C12N2501/25 ,  C12N2501/999

Abstract: This invention relates to stem cell microparticles, their use and production, in particular neural stem cell microparticles and their use in therapy. The stem cell microparticle is typically an exosome or microvesicle and may be derived from a neural stem cell line. The neural stem cell line may be a conditionally-immortalised stem cell line such as CTX0E03 (deposited at the ECACC with Accession No. 04091601).

Abstract translation: 本发明涉及干细胞微粒，其用途和生产，特别是神经干细胞微粒及其在治疗中的应用。 干细胞微粒通常是外来体或微泡，并且可以衍生自神经干细胞系。 神经干细胞系可以是有条件永生化的干细胞系，例如CTX0E03（保藏在ECACC，登录号04091601）。

公开(公告)号：US20160193252A1

公开(公告)日：2016-07-07

申请号：US14912060

申请日：2014-08-14

Applicant: RENEURON LIMITED

Inventor： Caroline Hicks ,  John Sinden ,  Lara Stevanato ,  Randolph Corteling

IPC: A61K35/30 ,  A61K9/127 ,  G01N33/50 ,  A61K31/7105

CPC classification number: A61K35/30 ,  A61K9/127 ,  A61K9/1277 ,  A61K31/7105 ,  C12N5/0623 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/30 ,  C12N2501/15 ,  C12N2501/24 ,  C12N2501/25 ,  C12N2502/088 ,  G01N33/5073

Abstract: This invention relates to stem cell microparticles and miRNA isolated from these microparticles, their use and production thereof, in particular neural stem cell microparticles and their use in therapy of a disease or condition involving unwanted or undesirable cell migration. The stem cell microparticle is typically an exosome or microvesicle and may be derived from a neural stem cell line. The neural stem cell line may be a conditionally-immortalised stem cell line such as CTX0E03 (deposited at the ECACC with Accession No. 04091601).

Abstract translation: 本发明涉及从这些微粒分离的干细胞微粒和miRNA，其使用和生产，特别是神经干细胞微粒及其在治疗涉及不想要的或不期望的细胞迁移的疾病或病症中的用途。 干细胞微粒通常是外来体或微泡，并且可以衍生自神经干细胞系。 神经干细胞系可以是有条件永生化的干细胞系，例如CTX0E03（保藏在ECACC，登录号04091601）。

公开(公告)号：US20150079046A1

公开(公告)日：2015-03-19

申请号：US14390010

申请日：2013-04-03

Applicant: RENEURON LIMITED

Inventor： John Sinden ,  Lara Stevanato ,  Randolph Corteling

IPC: A61K35/30 ,  G01N33/50 ,  C12N15/113

CPC classification number: A61K35/30 ,  A61K31/7105 ,  C12N5/0623 ,  C12N15/113 ,  C12N2310/141 ,  C12N2501/15 ,  C12N2501/24 ,  C12N2501/25 ,  C12N2502/088 ,  G01N33/5023 ,  A61K2300/00

Abstract: This invention relates to stem cell microparticles, their use and production, in particular neural stem cell microparticles and their use in therapy. The stem cell microparticle is typically an exosome or microvesicle and may be derived from a neural stem cell line. The neural stem cell line may be a conditionally-immortalised stem cell line such as CTX0E03 (deposited at the ECACC with Accession No. 04091601).

公开(公告)号：US20140341868A1

公开(公告)日：2014-11-20

申请号：US14450733

申请日：2014-08-04

Applicant: RENEURON LIMITED

Inventor： JOHN SINDEN ,  ERIK MILJAN ,  PAOLO MADEDDU

IPC: A61K35/30

CPC classification number: C12N5/0623 ,  A61K35/12 ,  A61K35/30 ,  C12N2510/04

Abstract: The present invention uses neural stem cells in the manufacture of a medicament for the treatment of a patient suffering peripheral arterial disease. The invention is particularly suited for treating limb ischemia or Buerger's disease.

Abstract translation: 本发明在制造用于治疗患有外周动脉疾病的患者的药物中使用神经干细胞。 本发明特别适用于治疗肢体缺血或Buerger病。

公开(公告)号：US20230227854A1

公开(公告)日：2023-07-20

申请号：US17633570

申请日：2020-08-10

Applicant: ReNeuron Limited

Inventor： Randolph CORTELING ,  Ruben DEOGRACIAS

IPC: C12N15/90 ,  C12N5/079 ,  C12N5/0783 ,  C12N5/0797 ,  A61K35/12 ,  A61K48/00

CPC classification number: C12N15/907 ,  C12N5/0622 ,  C12N5/0636 ,  C12N5/0623 ,  A61K35/12 ,  A61K48/005 ,  C12N2510/00

Abstract: This invention relates to genetic engineering, in particular to an insertion site for a transgene, cells comprising a transgene or other modification at that insertion site, vectors for targeting that insertion site, and methods for creating transgenic cells by insertion or other modification at that site. The insertion site, or “safe harbour locus”, is identified within the SPATA13 gene on human chromosome 13q12.12. Mammalian cells comprising a genetic modification within the SPATA13 gene on chromosome 13q12.12 are described, wherein the modification may be an insertion such as an integrated transgene. Nucleic acid molecules able and adapted to guide the insertion of a transgene to that insertion site are also described. These cells or nucleic acids may be useful in therapy.

公开(公告)号：US20210371828A1

公开(公告)日：2021-12-02

申请号：US17284428

申请日：2019-10-11

Applicant: ReNeuron Limited

Inventor： Steve PELLS ,  Randolph CORTELING ,  John Sinden

IPC: C12N5/074 ,  A61K35/545

Abstract: The invention relates to induced pluripotent stem cells that are generated from cells, for example Adult Stem Cells, that are conditionally-immortalisable. In particular, the invention relates to induced pluripotent stem cells generated from stem cell lines comprising a controllable transgene for conditional immortalisation, and the progeny of those induced pluripotent stem cells. Induced pluripotent stem cells, progeny cells derived from those pluripotent cells, compositions comprising those cells, methods of making all of those cells, and uses of all of those cells are also described.

公开(公告)号：US20160002597A1

公开(公告)日：2016-01-07

申请号：US14767280

申请日：2014-02-12

Applicant: Reneuron Limited

Inventor： John Sinden ,  Lara Stevanato ,  Randolph Corteling

IPC: C12N5/0797 ,  A61K35/12

CPC classification number: C12N5/0623 ,  A61K31/7105 ,  A61K35/12 ,  A61K35/30 ,  C12N5/0647 ,  C12N2500/90 ,  C12N2501/148 ,  C12N2501/15 ,  C12N2501/24 ,  C12N2501/25 ,  C12N2502/088 ,  C12N2502/1171

Abstract: The invention is based on the finding that microparticles can be produced by conditionally-immortalised cells. The conditionally-immortalised cells may be stem cells. The Examples show the successful harvest of microparticles from conditionally immortalised neural stem cells and CD34+ cells. Conditional immortalisation provides a constant supply of clonal cells that produce microparticles such as exosomes. The conditionally immortalised cells are useful as “producer cells” for microparticles such as exosomes, which are typically harvested or isolated from the conditionally-immortalised cells.

Abstract translation: 本发明是基于通过有条件永生化细胞产生微粒的发现。 有条件永生化的细胞可以是干细胞。 实施例显示从条件永生化神经干细胞和CD34 +细胞中成功收获微粒。 条件永生化提供了产生微粒例如外来体的克隆细胞的不断供应。 有条件永生化细胞可用作微粒例如外来体的“生产细胞”，其通常从有条件永生化细胞中收获或分离。

公开(公告)号：US20130045189A1

公开(公告)日：2013-02-21

申请号：US13660647

申请日：2012-10-25

Applicant: UNIVERSITY OF SOUTH FLORIDA ,  RENEURON LIMITED

Inventor： Paul R. Sanberg ,  John Sinden

IPC: A61K35/30 ,  A61P25/00 ,  A61P25/28

CPC classification number: C12N5/0623 ,  A61K35/12

Abstract: The subject invention pertains to methods to enhance the therapeutic effects of cellular or drug treatment in various diseases and disorders. More particularly, the present invention provides methods of treating disorders by administering CTX0E03 cells to the patient, intravenously or intraarterially. The treatment is useful for neurodegenerative diseases, such as stroke. The CTX0E03 cells may be cryopreserved and/or passaged before administration into the patient. Administration of the CTX0E03 cells into stroke rat models was at or within 48 hours after stroke. Testing of the rat models through elevated body swing test to measure of neurobehavioral status at the time of transplant and repeated triphenyltetrazolium chloride (TTC) staining as a measure of infarct volume showed short term survival that provided significant protection from the stroke.

Abstract translation: 本发明涉及增强细胞或药物治疗在各种疾病和病症中的治疗效果的方法。 更具体地，本发明提供了通过向患者静脉内或动脉内施用CTX0E03细胞来治疗疾病的方法。 治疗对于神经变性疾病如中风是有用的。 CTX0E03细胞可以在给予患者之前被冷冻保存和/或传代。 CTX0E03细胞进入中风大鼠模型是在中风后48小时内或之后。 通过升高的身体摆动测试来测试大鼠模型，以测量移植时的神经行为状态，并重复三苯基四氮唑（TTC）染色作为梗塞体积的量度，显示短期存活提供了显着的中风保护。

公开(公告)号：US20230287408A1

公开(公告)日：2023-09-14

申请号：US17785801

申请日：2020-12-18

Applicant: ReNeuron Limited

Inventor： Randolph CORTELING ,  Ruben DEOGRACIAS

IPC: C12N15/113 ,  C12N15/88 ,  C12N15/86

CPC classification number: C12N15/113 ,  C12N15/86 ,  C12N15/88 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2310/533 ,  C12N2320/32 ,  C12N2740/15043

Abstract: The invention delivers exogenous nucleotide sequences into exosomes using structural and regulatory characteristics identified in the miRNA molecules MIR21, pri-miR-21 and pre-miR- 21. In particular, the invention relates to pre-miRNA for targeting an exogenous nucleotide sequence to an exosome, wherein the pre-miRNA comprises an exogenous nucleotide sequence and a stem-loop structure, wherein the stem comprises at least one wobble pair. The invention also provides nucleic acid cassettes, vectors and cells comprising the engineered pre-miRNA, methods of loading exosomes and the resulting loaded exosomes. The loaded exosomes can be used to deliver an exogenous nucleotide sequence to a target cell, for example in therapy.