# US 11,439,662 B2 · Combined organ and hematopoietic cells for transplantation tolerance of grafts > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,662 B2 - Document ID: US11439662B2 - Status: Granted - Kind: B2 - Application number: 16/515,897 - Filed: 2019-07-18 - Published: 2019-11-28 - Granted: 2022-09-13 - Earliest claimed: 2013-02-26 - Assignees: The Board of Trustees of the Leland Stanford Junior University - Applicants: The Board of Trustees of the Leland Stanford Junior University - Inventors: Samuel Strober; Robert Lowsky - Web page: https://patentgrep.com/patent/US11439662B2 ## CPC - A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00) - A61K 31/365: Lactones - A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin - A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone - A61K 35/14: Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42) - A61K 35/22: Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 38/13: Cyclosporins - A61K 38/193: {Colony stimulating factors [CSF]} - A61K 39/001: {Preparations to induce tolerance to non-self, e.g. prior to transplantation} - A61K 39/39541: {against normal tissues, cells} - A61K 40/10: characterised by the cell type used - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/22: Immunosuppressive or immunotolerising - A61K 40/418: {Antigens related to induction of tolerance to non-self} - A61K 41/00: Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) - A61P 13/12: of the kidneys - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - C12N 5/0634: {Cells from the blood or the immune system} - C12N 5/0636: {T lymphocytes} - A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum - A61K 2035/122: {for inducing tolerance or supression of immune responses} - A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells} - A61K 2039/515: {Animal cells} - A61K 2039/54: {characterised by the route of administration} - A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2} - A61K 2239/31: characterized by the route of administration - A61K 2239/38: characterised by the dose, timing or administration schedule - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance. ## Claims ### Claim 1 A cellular product for establishing mixed chimerism in a solid organ transplant recipient, the product comprising: greater than 5×105 CD34+ cells/kg recipient weight; greater than 1×105 CD3+ cells/kg recipient weight; and a cell type that facilitates engraftment of the CD34+ cells and the CD3+ cells in a bone marrow of the recipient of the solid organ transplant. ### Claim 2 (depends on 1) The cellular product of claim 1, comprising at least about 10×106 CD34+ cells/kg recipient weight. ### Claim 3 (depends on 1) The cellular product of claim 1, comprising at least about 1×107 CD3+ cells/kg recipient weight. ### Claim 4 (depends on 1) The cellular product of claim 1, comprising at least about 10×106 CD34+ cells/kg recipient weight and at least about 1×107 CD3+ cells/kg recipient weight. ### Claim 5 (depends on 1) The cellular product of claim 1, wherein the cellular product is substantially devoid of platelets and red blood cells. ### Claim 6 (depends on 1) The cellular product of claim 1, wherein at least two of the CD34+ cells, the CD3+ cells, and the cell type that facilitates engraftment are provided in separate containers. ### Claim 7 (depends on 1) The cellular product of claim 1, wherein the CD34+ cells, the CD3+ cells, and the cell type that facilitates engraftment are provided as a mixture in a common container. ### Claim 8 (depends on 1) The cellular product of claim 1, wherein the CD34+ cells and the CD3+ cells are HLA matched to an HLA type of the solid organ transplant recipient. ### Claim 9 (depends on 1) The cellular product of claim 1, wherein the CD34+ cells and the CD3+ cells are HLA mismatched to an HLA type of the solid organ transplant recipient. ### Claim 10 (depends on 1) The cellular product of claim 1, wherein the CD34+ cells and the CD3+ cells are from a single apheresis product. ### Claim 11 A cellular product for establishing mixed chimerism in a solid organ transplant recipient, the product comprising: greater than 5×105 CD34+ cells/kg recipient weight; a defined amount of CD3+ cells/kg recipient weight; and a cell type that facilitates engraftment of the CD34+ cells and the CD3+ cells in a bone marrow of the recipient of the solid organ transplant. ### Claim 12 (depends on 11) The cellular product of claim 11, comprising at least about 10×106 CD34+ cells/kg recipient weight. ### Claim 13 (depends on 11) The cellular product of claim 11, wherein the defined amount of CD3+ cells/kg recipient weight is 10×107 CD3+ cells/kg recipient weight. ### Claim 14 (depends on 11) The cellular product of claim 11, comprising at least about 10×106 CD34+ cells/kg recipient weight and 10×107 CD3+ cells/kg recipient weight. ### Claim 15 (depends on 11) The cellular product of claim 11, wherein the cellular product is substantially devoid of platelets and red blood cells. ### Claim 16 (depends on 11) The cellular product of claim 11, wherein at least two of the CD34+ cells, the CD3+ cells, and the cell type that facilitates engraftment are provided in separate containers. ### Claim 17 (depends on 11) The cellular product of claim 11, wherein the CD34+ cells, the CD3+ cells, and the cell type that facilitates engraftment are provided as a mixture in a common container. ### Claim 18 (depends on 11) The cellular product of claim 11, wherein the CD34+ cells and the CD3+ cells are HLA matched to an HLA type of the solid organ transplant recipient. ### Claim 19 (depends on 11) The cellular product of claim 11, wherein the CD34+ cells and the CD3+ cells are HLA mismatched to an HLA type of the solid organ transplant recipient. ### Claim 20 (depends on 11) The cellular product of claim 11, wherein the CD34+ cells and the CD3+ cells are from a single apheresis product.