公开(公告)号：US10434121B2

公开(公告)日：2019-10-08

申请号：US14367923

申请日：2012-12-20

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig

IPC: A61K35/28 ,  A61K35/17 ,  A61K35/22 ,  A61K35/38 ,  A61K35/39 ,  A61K35/407 ,  A61K35/42 ,  A61K31/675 ,  A61K31/661 ,  A61K35/34 ,  A61K35/36 ,  C12N5/00 ,  A61K31/198 ,  A61K31/255 ,  A61K31/7076 ,  A61K39/395 ,  A61K39/00 ,  A61K35/12

Abstract: A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoetic cells, wherein the T cell depleted immature hematopoetic cells comprise less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×106 CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoetic cells are obtained by separating the T cells from the immature hematopoetic cells by magnetic cell sorting, and (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per body weight, thereby treating the subject.

公开(公告)号：US12133866B2

公开(公告)日：2024-11-05

申请号：US17735146

申请日：2022-05-03

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Yaki Eidelstein ,  Eran Ophir ,  Assaf Lask ,  Ran Afik ,  Noga Or-Geva ,  Esther Bachar-Lustig

IPC: A61K35/17 ,  A61K35/12 ,  A61K35/22 ,  A61K35/26 ,  A61K35/28 ,  A61K35/34 ,  A61K35/36 ,  A61K35/38 ,  A61K35/39 ,  A61K35/407 ,  A61K35/42 ,  A61K39/00 ,  C12N5/0783

Abstract: A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) contacting peripheral blood mononuclear cells (PBMC) with a third party antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (b) culturing the cells resulting from step (a) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment so as to allow proliferation of cells comprising the central memory T-lymphocyte (Tcm) phenotype.

公开(公告)号：US11773372B2

公开(公告)日：2023-10-03

申请号：US17211863

申请日：2021-03-25

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Noga Or-Geva ,  Rotem Gidron Budovsky ,  Esther Bachar-Lustig ,  Assaf Lask ,  Sivan Kagan

IPC: C12N5/0783 ,  A61K35/17 ,  A61K39/00 ,  C12N5/00 ,  A61K35/12

CPC classification number: C12N5/0637 ,  A61K35/17 ,  A61K39/001 ,  C12N5/0087 ,  A61K2035/122 ,  A61K2039/5158 ,  C12N2501/2307 ,  C12N2501/2315 ,  C12N2501/2321 ,  C12N2502/1121

Abstract: A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

公开(公告)号：US11504399B2

公开(公告)日：2022-11-22

申请号：US16538954

申请日：2019-08-13

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig

IPC: A61K35/17 ,  A61K35/22 ,  A61K35/28 ,  A61K35/38 ,  A61K35/39 ,  A61K35/407 ,  A61K35/42 ,  A61K31/675 ,  A61K35/34 ,  A61K35/36 ,  C12N5/00 ,  A61K31/198 ,  A61K31/255 ,  A61K31/7076 ,  A61P37/06 ,  A61P37/02 ,  A61K31/661 ,  A61K39/395 ,  A61K39/00 ,  A61K35/12

Abstract: A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoietic cells are obtained by separating the T cells from the immature hematopoietic cells by magnetic cell sorting, and (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per body weight, thereby treating the subject.

公开(公告)号：US20140363437A1

公开(公告)日：2014-12-11

申请号：US14367917

申请日：2012-12-20

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig

IPC: A61K35/28 ,  A61K31/7076 ,  A61K31/661 ,  A61K39/395

CPC classification number: A61K35/28 ,  A61K31/198 ,  A61K31/255 ,  A61K31/661 ,  A61K31/675 ,  A61K31/7076 ,  A61K35/22 ,  A61K35/34 ,  A61K35/36 ,  A61K35/38 ,  A61K35/39 ,  A61K35/407 ,  A61K35/42 ,  A61K39/3955 ,  A61K2035/124 ,  A61K2039/507 ,  A61K2039/515 ,  C12N5/0087 ,  A61K2300/00

Abstract: A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×106 CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.

Abstract translation: 公开了一种治疗需要非同基因细胞或组织移植物的受试者的方法。 该方法包括：（a）向受试者移植一定剂量的T细胞耗尽的未成熟造血细胞，其中所述T细胞耗尽的未成熟造血细胞每个体重为每公斤体重小于5×10 5个CD3 + T细胞，其中所述剂量 每公斤体重至少约5×106个CD34 +细胞; 并且随后（b）向受试者施用治疗有效量的环磷酰胺，其中治疗有效量包含25-200mg /千克体重，从而治疗受试者。

公开(公告)号：US11555178B2

公开(公告)日：2023-01-17

申请号：US16478477

申请日：2018-01-18

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig ,  Shlomit Reich-Zeliger

IPC: C12N5/0783 ,  A61P35/02 ,  A61P35/04 ,  A61P35/00 ,  A61K35/17 ,  C07K14/725 ,  C07K16/28 ,  C07K16/30 ,  C07K16/32 ,  C12N5/00 ,  A61K38/00

Abstract: An isolated cytotoxic T-lymphocyte (CTL), said CTL being a tolerance inducing cell and substantially depleted of alloreactivity, and wherein said CTL does not comprise a central memory T-lymphocyte (Tcm) phenotype, the CTL being transduced to express a cell surface receptor comprising a T cell receptor signaling module, is disclosed. Methods of generating same and using same are also disclosed.

公开(公告)号：US10751368B2

公开(公告)日：2020-08-25

申请号：US15873943

申请日：2018-01-18

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig ,  Shlomit Reich-Zeliger

IPC: A61K35/17 ,  C07K16/28 ,  A61P35/00 ,  A61K35/28 ,  A61K39/395

Abstract: A method of transplantation is disclosed. The method comprising administering to a subject in need of transplantation of cells in suspension, a therapeutically effective amount of tolerance inducing anti-third party cytotoxic T-lymphocytes (CTLs), wherein the tolerance inducing anti-third party CTLs are generated by directing T-lymphocytes of a donor against a third party antigen or antigens, the tolerance inducing anti-third party CTLs being substantially depleted of T-lymphocytes capable of developing into alloreactive CTLs, and wherein the tolerance inducing anti-third party CTLs do not comprise cells having a central memory T-lymphocyte (Tcm) phenotype, wherein the cells in suspension comprise non-hematopoietic cells or hematopoietic cells which are not stem cells. Methods of treating and kits are also provided.

公开(公告)号：US10369172B2

公开(公告)日：2019-08-06

申请号：US14367917

申请日：2012-12-20

Applicant: Yeda Research and Development Co. Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig

IPC: A61K35/28 ,  A61K35/17 ,  A61K35/22 ,  A61K35/38 ,  A61K35/39 ,  A61K35/407 ,  A61K35/42 ,  A61K31/675 ,  A61K35/34 ,  A61K35/36 ,  C12N5/00 ,  A61K31/198 ,  A61K31/255 ,  A61K31/7076 ,  A61K31/661 ,  A61K39/395 ,  A61K39/00 ,  A61K35/12

Abstract: A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The method comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoietic cells, wherein the T cell depleted immature hematopoietic cells comprise less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×106 CD34+ cells per kilogram body weight of the subject; and subsequently (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per kilogram body weight, thereby treating the subject.

公开(公告)号：US20190091266A1

公开(公告)日：2019-03-28

申请号：US16198811

申请日：2018-11-22

Applicant: Yeda Research and Development Co., Ltd.

Inventor： Yair Reisner ,  Carmit Hillel-Karniel ,  Chava Rosen ,  Esther Bachar-Lustig ,  Elias Shezen

IPC: A61K35/42 ,  A61K35/28 ,  A61K9/00 ,  A61P11/00

Abstract: A method of treating a pulmonary disorder or injury in a subject in need thereof is disclosed. The method comprising administering to the subject non-syngeneic pulmonary tissue cells in suspension comprising an effective amount of hematopoietic precursor cells (HPCs) or supplemented with HPCs, wherein the effective amount is a sufficient amount to achieve tolerance to the pulmonary tissue cells in the absence of chronic immunosuppressive regimen. A method of inducing donor specific tolerance in a subject in need of a pulmonary cell or tissue transplantation is also disclosed.

公开(公告)号：US20140369974A1

公开(公告)日：2014-12-18

申请号：US14367923

申请日：2012-12-20

Applicant: Yeda Research and Development Co., Ltd.

Inventor： Yair Reisner ,  Esther Bachar-Lustig

IPC: A61K35/28 ,  A61K31/675

CPC classification number: A61K35/28 ,  A61K31/198 ,  A61K31/255 ,  A61K31/661 ,  A61K31/675 ,  A61K31/7076 ,  A61K35/22 ,  A61K35/34 ,  A61K35/36 ,  A61K35/38 ,  A61K35/39 ,  A61K35/407 ,  A61K35/42 ,  A61K39/3955 ,  A61K2035/124 ,  A61K2039/507 ,  A61K2039/515 ,  C12N5/0087 ,  A61K2300/00

Abstract: A method of treating a subject in need of a non-syngeneic cell or tissue graft is disclosed. The methos comprising: (a) transplanting into a subject a dose of T cell depleted immature hematopoetic cells, wherein the T cell depleted immature hematopoetic cells comprise less than 5×105 CD3+ T cells per kilogram body weight of the subject, and wherein the dose comprises at least about 5×106 CD34+ cells per kilogram body weight of the subject, and wherein the T cell depleted immature hematopoetic cells are obtained by separating the T cells from the immature hematopoetic cells by magnetic cell sorting, and (b) administering to the subject a therapeutically effective amount of cyclophosphamide, wherein the therapeutically effective amount comprises 25-200 mg per body weight, thereby treating the subject.

Abstract translation: 公开了一种治疗需要非同基因细胞或组织移植物的受试者的方法。 该方法包括：（a）将一定剂量的T细胞耗尽的未成熟造血细胞移植到受试者中，其中所述T细胞耗尽的未成熟造血细胞每个体重为每公斤体重小于5×10 5个CD3 + T细胞，其中所述剂量 包括至少约5×106个CD34 +细胞/千克体重的受试者，并且其中所述T细胞耗尽的未成熟造血细胞是通过磁细胞分选从未成熟的造血细胞分离T细胞获得的，和（b） 患有治疗有效量的环磷酰胺，其中治疗有效量包含25-200mg /体重，从而治疗受试者。