Medium Contains An Interleukin Patents (Class 435/386)
  • Patent number: 7029671
    Abstract: The invention relates to a method for activating human-derived antigen-presenting cells by in vitro cultivation with at least one of the glycoside compounds represented by formula (A) or salts thereof [preferred example: (2S,3S,4R)-1-(?-D-galactopyranosyloxy)-2-hexacosanoylamino-3,4-octadecanediol], and to human antigen-presenting cells activated by the method. The invention also relates to a method for treatment of cancer and infectious diseases including AIDS with the activated human antigen-presenting cells, and to a use of the activated human antigen-presenting cells in the preparation of medicines for treating such diseases. The invention can provide a satisfactory therapeutic effect on cancer and infectious diseases including AIDS without the need to pulse the human antigen-presenting cells with tumor antigens.
    Type: Grant
    Filed: November 27, 2000
    Date of Patent: April 18, 2006
    Assignee: Kirin Brewery Company, Limited
    Inventors: Yasuhiko Koezuka, Yasunori Yamaguchi, Kazuhiro Motoki
  • Patent number: 6982168
    Abstract: The present invention relates to immortalized, malignant, human, adult prostate epithelial cell lines or cell lines derived therefrom useful in the diagnosis and treatment of prostate cancer. More particularly, the present invention relates to cloned, immortalized, malignant, human, adult prostate epithelial cell lines and uses of these cell lines for the diagnosis and treatment of cancer. Furthermore, the present invention provides for the characterization of said cell lines through the analysis of specific chromosomal deletions.
    Type: Grant
    Filed: January 30, 1997
    Date of Patent: January 3, 2006
    Assignee: The United States of America as represented by the Department of Health and Human Services
    Inventors: Suzanne L. Topalian, W. Marston Linehan, Robert K. Bright, Cathy D. Vocke
  • Patent number: 6969609
    Abstract: The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+and CD8+T cells.
    Type: Grant
    Filed: November 12, 1999
    Date of Patent: November 29, 2005
    Assignee: The United States of America as represented by the Department of Health and Human Serivces
    Inventors: Jeffrey Schlom, James Hodge, Dennis Panicali
  • Patent number: 6960473
    Abstract: We describe a new two-step culture method for mass production in vitro of erythroid cells from either CD34+ (105 cells/mL) or light-density (106 cells/mL) cells purified from the blood of normal donors and thalassemic patients. The method includes (i) culture of the cells in the presence of dexamethasone and estradiol (10?6 M each) and (ii) the growth factors SCF (50 ng/mL), IL-3 (1 ng/mL), and EPO (1 U/mL). In their proliferative phase, these cultures generated about 1-2×107 erythroblasts for each milliliter of blood collected from normal donors or thalassemic patients. They were composed mostly (90%) of CD45low/glycophorin (GPA)neg/CD71low cells at day 7, 50-60% of which became CD45neg/GPA+/CD71high by days 15-20. However, when cells from days 7 to 12 of the proliferative phase were transferred in differentiation medium containing EPO and insulin, they progressed to mature erythroblasts (>90% benzidinepos and CD45neg/GPA+/CD71medium) in 4 days.
    Type: Grant
    Filed: February 26, 2004
    Date of Patent: November 1, 2005
    Assignee: Istituto Superiore di Sanita
    Inventors: Giovanni Migliaccio, Anna Rita Franco
  • Patent number: 6919206
    Abstract: Ligands for flt3 receptors capable of transducing self-renewal signals to regulate the growth, proliferation or differentiation of progenitor cells and stem cells are disclosed. The invention is directed to flt3-L as an isolated protein, the DNA encoding the flt3-L, host cells transfected with cDNAs encoding flt3-L, compositions comprising flt3-L, methods of improving gene transfer to a mammal using flt3-L, and methods of improving transplantations using flt3-L. Flt3 -L finds use in treating patients with anemia, AIDS and various cancers.
    Type: Grant
    Filed: December 19, 1997
    Date of Patent: July 19, 2005
    Assignee: Immunex Corporation
    Inventors: Stewart D. Lyman, M. Patricia Beckmann
  • Patent number: 6838081
    Abstract: The present invention provides methods for enhancing the development of APC from precursor cells by administering a combination of GM-CSF and IL-4. The precursor cells include: cells contained in peripheral blood, CD14+ cells and precursors in bone marrow. Thus, administration of GM-CSF and IL-4 can be used as a form of cytokine immunotherapy. One embodiment of the present invention involves systemic administration of GM-CSF and IL-4. In this embodiment, APC are required to directly access tumor antigens as they exist in vivo within the patient. A further embodiment of the present invention involves co-administration of a tumor-associated or tumor-specific antigen, with GM-CSF and IL-4, to induce antigen-specific immunity mediated by APC. Yet another embodiment of the present invention describes systemic administration of GM-CSF and IL-4 to achieve reduced tumor burden.
    Type: Grant
    Filed: April 2, 1999
    Date of Patent: January 4, 2005
    Assignee: The Regents of the University of California
    Inventors: Michael Derek Roth, Robert Alan Figlin, Sylvia Marie Kiertscher, Barbara Jennifer Gitlitz
  • Patent number: 6828147
    Abstract: TALL-104 cells, and other cytotoxic T cell lines, may be modified to increase the cytotoxicity thereof, to enhance growth properties, and/or to provide a preferred phenotype, e.g., expression of cell surface antigens, function, e.g., change in cytokine production profile, by culturing the cells in an effective amount of IL-15, optionally followed by gamma irradiation to halt proliferation.
    Type: Grant
    Filed: August 21, 2001
    Date of Patent: December 7, 2004
    Assignee: The Wistar Institute of Anatomy and Biology
    Inventors: Daniela Santoli, Giovanni Rovera, Alessandra Cesano
  • Patent number: 6805869
    Abstract: The present invention provides a method for enhancing the immunogenicity of weakly immunogenic or non-immunogenic cells, resulting in a cellular vaccine that can stimulate T cell activation, which in turn leads to an effective immune response. The cellular vaccines of the present invention are useful for the prevention and treatment of diseases which develop and/or persist by escaping the immune response triggered by T cell activation. Such diseases include, for example, all cancers, natural and induced immune deficiency states, and diseases caused by infections with a variety of pathogens.
    Type: Grant
    Filed: December 17, 1998
    Date of Patent: October 19, 2004
    Assignee: Shanghai CP Guojian Pharmaceutical Co., Ltd.
    Inventor: Yajun Guo
  • Patent number: 6733746
    Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.
    Type: Grant
    Filed: January 31, 1997
    Date of Patent: May 11, 2004
    Assignee: Invitrogen Corporation
    Inventors: John P. Daley, Barbara M. Dadey, William C. Biddle, Michelle G. Wysocki
  • Patent number: 6692958
    Abstract: Activated lymphocytes derived from cord blood are excellently effective for preventing and treating various types of tumors and various types of infection. With interleukin 2 and/or anti-CD3 antibody, the lymphocytes derived from the cord blood is prepared by segregating lymphocytes from the cord blood and proliferating the segregated lymphocytes directly in vitro or segregating monocytes from cord blood and proliferating the monocytes in vitro. Also, the cord blood-derived activated lymphocytes can be effectively used for preventing recurrence of the diseases and promoting the take of stem cells or other organs.
    Type: Grant
    Filed: December 4, 2001
    Date of Patent: February 17, 2004
    Assignee: Humantec Ltd.
    Inventors: Teruaki Sekine, Kiminari Ito, Norio Shimizu, Kenzo Bamba, Tomohiro Yamaguchi, Yasuyuki Kuroiwa
  • Publication number: 20040019390
    Abstract: The present invention relates, generally, to methods and compositions for allogeneic transplantation. More particularly, the invention relates to the use of alloreactive natural killer cells in order to enhance the efficacy and/or safety of allogeneic grafts in human subjects. The invention allows to increase the engraftment of an allogeneic grafts, even in myelo-reductive conditioning, to protect against GVHD and/or to eradicate malignant cells. The invention is particularly suited in allogeneic hematopoietic transplantations, particularly bone marrow transplantations.
    Type: Application
    Filed: March 11, 2003
    Publication date: January 29, 2004
    Inventor: Andrea Velardi
  • Patent number: 6667034
    Abstract: Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium.
    Type: Grant
    Filed: May 16, 1997
    Date of Patent: December 23, 2003
    Assignee: The Regents of the University of Michigan
    Inventors: Bernhard O. Palsson, R. Douglas Armstrong, Michael F. Clarke, Stephen G. Emerson
  • Patent number: 6645487
    Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD 34-hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.
    Type: Grant
    Filed: December 20, 2000
    Date of Patent: November 11, 2003
    Inventors: Cem Cezayirli, Mel Silvers
  • Publication number: 20030134419
    Abstract: A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.
    Type: Application
    Filed: November 5, 2002
    Publication date: July 17, 2003
    Inventors: Ralph M. Steinman, Kayo Inaba, Gerold Schuler
  • Patent number: 6586243
    Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD 34− hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.
    Type: Grant
    Filed: December 20, 2000
    Date of Patent: July 1, 2003
    Inventors: Cem Cezayirli, Mel Silvers
  • Patent number: 6558949
    Abstract: This invention relates to media for culturing human cells that the proliferation speed of human cells is increased and the cell expression type is stably manifested, and to a method for culturing human cells using the same. This invention is characterized in that the media used for culturing human cells comprises human serum.
    Type: Grant
    Filed: December 13, 2000
    Date of Patent: May 6, 2003
    Inventors: Byoung-Hyun Min, So Ra Park
  • Patent number: 6511848
    Abstract: A method for culturing and/or multiplying lymphocytes in cell culture medium which contains as lymphocyte growth factor and additionally, aurin tricarboxylic acid, ciclosporin, tacrolimus, and/or ascomycin.
    Type: Grant
    Filed: November 12, 1998
    Date of Patent: January 28, 2003
    Assignee: Winfried Albert
    Inventors: Herbert Jungfer, Heinrich Barchet, Winfried Albert
  • Publication number: 20020182730
    Abstract: Compositions containing clinically relevant numbers of immune cells that have been isolated from a patient differentiated and/or expanded ex vivo. Methods for treating or preventing disease or otherwise altering the immune status of the patient by reinfusing such cells into the donor are also provided. Methods for expanding and/or immune cells, including effector cells, in the absence of exogenous IL-2, and for administering the cells in the absence of co-infused IL-2 are also provided.
    Type: Application
    Filed: July 31, 1998
    Publication date: December 5, 2002
    Inventor: MICHEAL L. GRUENBERG
  • Publication number: 20020182178
    Abstract: The invention relates to the use of IL-15 or active variants thereof and/or IL-15 activity enhancing compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system, such as manipulating viability ad/or responsiveness of said memory cells. The IL-15 activity enhancing compound is for example lipopolysaccharide (LPS). The invention further relates to the use of IL-15 inhibiting or eliminating compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system. Such inhibiting or eliminating compounds are for example anti-IL-15 antibodies, anti-IL-15R&agr; antibodies, fragments of these antibodies, e.g. the Fab or F(ab′)2 fragment, soluble IL-15R&agr;, fusion proteins consisting of soluble IL-15R&agr;, and Fc fragment, compounds, e.g. peptides, binding-and/or inhibiting functional IL-15 receptor, IL-15 antisense oligonucleotides.
    Type: Application
    Filed: October 18, 2001
    Publication date: December 5, 2002
    Inventors: Johan Adriaan Marc Grooten, Hans Peter Raf Dooms, Walter Charles Fiers
  • Patent number: 6432711
    Abstract: An embryonic stem cell which may be induced to differentiate homogeneously into a desired primary cell line. The embryonic stem cell may be engineered with DNA, which encodes a protein or polypeptide which promotes differentiation of the stem cell into a specific cell line, such as, for example, a neuronal cell line, a muscle cell line, or a hematopoietic cell line. The DNA may encode a transcription factor found in the particular cell line. In another alternative, a desired cell line is produced from embryonic stem cells by culturing embryonic stem cells under conditions which provide for a three-dimensional network of embryonic stem cells, and then stimulating embryonic stem cells with an agent, such as retinoic acid, or dimethylsulfoxide, which promotes differentiation of the embryonic stem cells into the desired cell line, such as, for example, a neuronal cell line, or a muscle cell line.
    Type: Grant
    Filed: November 1, 1994
    Date of Patent: August 13, 2002
    Assignee: Diacrin, Inc.
    Inventors: Jonathan H. Dinsmore, Judson Ratliff
  • Patent number: 6355237
    Abstract: The present invention relates to methods for using various forms of a novel receptor expressed by hematopoietic and endothelial cells. An additional variant form of this receptor has been detected in brain cells and shown to bind to the obese gene product, leptin. Therefore, leptin may be used to stimulate the growth and development of receptor-positive hematopoietic and endothelial cells in vitro and in vivo. In addition, this receptor is selectively expressed in hematopoietic progenitor cells with long-term repopulating potential. Thus, agents that specifically bind to this receptor may be used to identify and isolate progenitor cells for a variety of clinical applications.
    Type: Grant
    Filed: March 20, 1996
    Date of Patent: March 12, 2002
    Assignee: Progenitor, Inc.
    Inventors: H. Ralph Snodgrass, Joseph Cioffi, Thomas Joel Zupancic, Alan Wayne Shafer
  • Patent number: 6344192
    Abstract: The invention relates to the use of IL-15 or active variants thereof and/or IL-15 activity enhancing compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system, such as manipulating viability ad/or responsiveness of said memory cells. The IL-15 activity enhancing compound is for example lipopolysaccharidc (LPS). The invention further relates to the use of IL-15 inhibiting or eliminating compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system. Such inhibiting or eliminating compounds are for example anti-IL-15 antibodies, anti-IL-15R&agr; antibodies, fragments of these antibodies, e.g. the Fab or F(ab′)2 fragment, soluble IL-15R&agr;, fusion proteins consisting of soluble IL-15R&agr;, and Fc fragment, compounds, e.g. peptides, binding and/or inhibiting functional IL-15 receptor, IL-15 antisense oligonucleotides.
    Type: Grant
    Filed: August 23, 1999
    Date of Patent: February 5, 2002
    Assignee: Vlaams Interuniversitair Instituut voor Biotechnologie
    Inventors: Johan Adriaan Marc Grooten, Hans Peter Raf Dooms, Walter Charles Fiers
  • Patent number: 6316257
    Abstract: The present invention provides a modified rapid expansion method (termed “low-PBMC-REM” or “modified-REM”), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes, without using the large excesses of peripheral blood mononuclear cells (PBMC) or EBV-transformed lymphoblastoid cells (LCL) characteristic of high-PBMC-REM. Clonal expansions of greater than 500-fold can be achieved within a single stimulation cycle of about 8-14 days.
    Type: Grant
    Filed: March 3, 1997
    Date of Patent: November 13, 2001
    Assignee: Targeted Genetics Corporation
    Inventors: David C. Flyer, Kim W. Clary
  • Publication number: 20010033835
    Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.
    Type: Application
    Filed: January 31, 1997
    Publication date: October 25, 2001
    Inventors: JOHN P. DALEY, BARBARA M. DADEY, WILLIAM C. BIDDLE, MICHELLE G. WYSOCKI
  • Patent number: 6251665
    Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD34− hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.
    Type: Grant
    Filed: February 3, 1998
    Date of Patent: June 26, 2001
    Inventors: Cem Cezayirli, Mel Silvers
  • Patent number: 6251671
    Abstract: The invention relates to cell proliferation, cell differentiation, male infertility, male fertility and to compositions and methods involved therein. Also methods of culturing spermatogonial stem cells with bone morphogenetic protein 8 are disclosed.
    Type: Grant
    Filed: February 28, 1997
    Date of Patent: June 26, 2001
    Assignee: Vanderbilt University
    Inventors: Brigid L. M. Hogan, Guang-Quan Zhao
  • Patent number: 6165785
    Abstract: A method of treatment using immune system suppressor cells and immune system stimulator cells comprises providing stem cells; combining the stem cells with lymphoid-derived cells to produce a co-culture; adding lipopolysaccharide and a factor selected from the group consisting of granulocyte macrophage-colony stimulating factor, macrophage colony stimulating factor, granulocyte-colony stimulating factor and mixtures thereof to the co-culture; obtaining immune system suppressor cells and immune system stimulator cells from the co-culture; and introducing and the cells into a host.
    Type: Grant
    Filed: October 23, 1998
    Date of Patent: December 26, 2000
    Assignees: University of Cincinnati, Shriners Hospitals for Children
    Inventors: Cora K. Ogle, John F. Valente, J. Wesley Alexander
  • Patent number: 6114168
    Abstract: A culture medium for culturing chicken embryonic stem (ES) cells is disclosed. The culture medium is used for supporting avian ES cell cultures. The components of the avian ES cell media include cytokines, fibroblast growth factors, insulin-like growth factors and stem cell growth factors and anti-retinoic acid antibody. The culture medium is substantially free of active retinoic acid. A method for culturing avian ES cells and the resulting products are also disclosed.
    Type: Grant
    Filed: May 12, 1997
    Date of Patent: September 5, 2000
    Assignees: Institute National de la Recherche Agronomique, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Superieure de Lyon
    Inventors: Jacques Samarut, Bertrand Pain
  • Patent number: 6110739
    Abstract: The present invention relates to novel immortalized precursor cell populations derived from embryonic stem cell populations and methods to produce such cell populations. Also disclosed is an assay to identify regulatory compounds capable of controlling cell growth for therapeutic and experimental use.
    Type: Grant
    Filed: February 22, 1999
    Date of Patent: August 29, 2000
    Assignee: National Jewish Medical and Research Center
    Inventors: Gordon M. Keller, Robert G. Hawley, Kyunghee Choi
  • Patent number: 6077519
    Abstract: Methods are provided for eluting peptides that are bound to major histocompatibility complex ("MHC") molecules expressed on the cell surfaces of viable cells that have at least one MHC-peptide complex on the surfaces of the cells. Methods are provided for using such acid-eluted T cell epitopes, preferably obtained from a patient's tumor, and autologous dendritic cells as the basis for antitumor vaccines.
    Type: Grant
    Filed: January 15, 1997
    Date of Patent: June 20, 2000
    Assignee: University of Pittsburgh
    Inventors: Walter J. Storkus, Michael T. Lotze
  • Patent number: 6004812
    Abstract: The present invention provides an in vitro T-lymphopoiesis system in which a population of T-cells is produced from precursor cells expressing CD34. The T-lymphopoiesis system of the present invention produces a population of T-cells of which approximately 17-74% express CD2, approximately 1.5-34% express CD3, and approximately 16-61% express CD4, and approximately 0-15% express CD8. A method of producing such a population of T-cells in vitro, as well as various compositions including T-cells of the present invention, are also provided.
    Type: Grant
    Filed: August 11, 1998
    Date of Patent: December 21, 1999
    Assignee: Beth Israel Medical Center, Inc.
    Inventors: David T. Scadden, Andrew Freedman
  • Patent number: 5958774
    Abstract: A method is disclosed for gene transfer into a culture of primitive stem cells which comprises a prestimulation step of adding a blocking agent to block at least one inhibitor of a cell cycle of said primitive stem cells. The prestimulation is time-limited for a period of less than approximately 36 hours so that said culture of primitive stem cells retains hematopoietic potential.
    Type: Grant
    Filed: July 10, 1997
    Date of Patent: September 28, 1999
    Assignee: Centre National de la Recherche Scientifique
    Inventors: Antoinette Klein, Jacques Hatzfeld
  • Patent number: 5928639
    Abstract: Methods have been discovered for treating minimal residual disease following removal of most or a substantial fraction of malignant cells from a cancer patient. An autologous stem cell transplant is performed on the patient. Following partial hematopoiesis recovery, the patient is infused with allogeneic peripheral blood lymphocytes, either alone or in combination with in vivo or in vitro cytokine. The infused allogeneic lymphocytes engender an anti-malignant cell response and can be instrumental in prevention of disease relapse.
    Type: Grant
    Filed: October 23, 1996
    Date of Patent: July 27, 1999
    Assignee: Hadasit Medical Research Services and Development Ltd.
    Inventor: Shimon Slavin
  • Patent number: 5919700
    Abstract: The invention relates to a method of stimulating the proliferation of natural killer cells with in vitro IL-16. A mixed lymphocyte cell population which contains natural killer cells can be nylon wool-purified, and cultured in the presence of an effective amount of IL-16 to stimulate the proliferation of natural killer cells. Effective concentrations of IL-16 which enhance the proliferation of natural killer cells range from 1 ng/ml to 1000 ng/ml. Both the full length IL-16 protein or the naturally occurring carboxy terminal-truncated form of IL-16 are suitable for stimulating the proliferation of the natural killer cells. The IL-16 induced proliferation results in at least a five-fold enrichment of natural killer cells, and the natural killer cells can be subsequently isolated from the mixed lymphocyte culture.
    Type: Grant
    Filed: August 23, 1996
    Date of Patent: July 6, 1999
    Assignee: MCW Research Foundation
    Inventors: Ernest C. Borden, Jonathan D'Cunha
  • Patent number: 5914268
    Abstract: The present invention relates to novel pluripotent embryonic cell populations derived from embryonic stem cell populations and methods to produce such pluripotent embryonic cell populations. Disclosed is an embryonic stem cell-derived pluripotent embryoid body cell population having one or more cells capable of developing into cells of hematopoietic and/or endothelial lineage. Also disclosed is an embryoid body cell population-derived mixed population of endothelial and erythroid cells. Also disclosed is an embryoid body cell population-derived embryonic blast cell population capable of developing into a variety of hematopoietic cell types. The invention is additionally directed to embryonic stem cell population-derived T and B cell populations. Methods to identify embryonic cell compounds are also disclosed for therapeutic and experimental use.
    Type: Grant
    Filed: November 21, 1994
    Date of Patent: June 22, 1999
    Assignee: National Jewish Center for Immunology & Respiratory Medicine
    Inventors: Gordon M. Keller, Marion Kennedy, Kyunghee Choi, Meri T. Firpo
  • Patent number: 5874301
    Abstract: The present invention relates to novel immortalized precursor cell populations derived from embryonic stem cell populations and methods to produce such cell populations. Also disclosed is an assay to identify regulatory compounds capable of controlling cell growth for therapeutic and experimental use.
    Type: Grant
    Filed: December 11, 1995
    Date of Patent: February 23, 1999
    Assignee: National Jewish Center for Immunology and Respiratory Medicine
    Inventors: Gordon M. Keller, Robert G. Hawley, Kyunghee Choi
  • Patent number: 5874308
    Abstract: Methods and compositions are provided for in vitro expansion of growth factor dependent cells. Expansion is effected through the use of growth factor conjugates that include a growth factor such as a steel factor and a polysaccharidase substrate binding region. The conjugates are immobilized by binding of the substrate binding region to a substrate of the polysaccharidase in a growth chamber for the cells.
    Type: Grant
    Filed: January 16, 1996
    Date of Patent: February 23, 1999
    Assignee: University of British Columbia
    Inventors: Douglas G. Kilburn, Keith R. Humphries, James G. Doheny, Eric Jervis, Judie Alimonti
  • Patent number: 5861315
    Abstract: Stem cell factor in combination with soluble interleukin-6 receptor, interleukin-6, for gp130 signaling, supports the proliferation, differentiation and terminal maturation of blood cells from normal human hematopoietic multipotential cells.
    Type: Grant
    Filed: October 16, 1996
    Date of Patent: January 19, 1999
    Assignees: Amgen Inc., Tosoh Corporation
    Inventor: Tatsutoshi Nakahata
  • Patent number: 5846827
    Abstract: Methods for activating cytotoxic T lymphocytes (CTL) in vitro are presented in conjunction with methods for using the activated CTL for therapy in vivo. Additionally, a method for killing specific CTL in vivo is presented using antigen presenting cells which were modified in vitro.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: December 8, 1998
    Assignee: Cytel Corporation
    Inventors: Esteban Celis, Ralph Kubo, Horacio Serra, Van Tsai, Peggy Wentworth
  • Patent number: 5830464
    Abstract: The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule in combination with administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex when administered intradermally are in the range of 0.
    Type: Grant
    Filed: February 7, 1997
    Date of Patent: November 3, 1998
    Assignee: Fordham University
    Inventor: Pramod K. Srivastava
  • Patent number: 5827642
    Abstract: The present invention provides a rapid expansion method (termed "REM"), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes. REM involves culturing the T cells in association with a disproportionately large concentration of nondividing feeder cells, preferably .gamma.-irradiated peripheral blood mononuclear cells ("PBMC") present at an excess of at least 40-fold (relative to the number of target T cells), more preferably at an excess of at least about 200-fold. Cultures grown under REM exhibit dramatically enhanced expansion rates that can be even further elevated by the use of appropriate concentrations of an additional feeder cell, an anti-CD3 monoclonal antibody and IL-2, as described herein. Clonal expansions in the range of 500-fold to 3000-fold can be achieved within a single stimulation cycle of about 10-13 days, which is more than 100-fold more efficient than currently employed methods of culturing human T cell clones.
    Type: Grant
    Filed: October 3, 1994
    Date of Patent: October 27, 1998
    Assignee: Fred Hutchinson Cancer Research Center
    Inventors: Stanley R. Riddell, Philip D. Greenberg
  • Patent number: 5811301
    Abstract: In vitro production of clinically useful quantities of single species of mature, differentiated human blood cells is carried out by a method in which human pluripotent hematopoietic stem cells, preferably from a universal donor, are incubated in a bioreactor in a growth medium also containing specific combinations of recombinant human growth and maturation promoting polypeptide factors that expand stem cell cultures and promote the maturation and differentiation of stem cells into single species of erythroid, thrombocytic or granulocytic human blood cells, and harvesting the mature cells. The growth and maturation promoting polypeptides employed include SCGF, Interleukins 1,3,4,5,6, and 11, GM-CSF, M-CSF, G-CSF and EPO. Stem cells may be preliminarily genetically modified so as to remove histocompatibility or blood group antigens with which a recipient may be incompatible, or the stem cells may be genetically altered by transfection with appropriate DNA-containing vectors, prior to addition to the bioreactor.
    Type: Grant
    Filed: August 7, 1996
    Date of Patent: September 22, 1998
    Inventor: Robert B. Cameron
  • Patent number: 5807744
    Abstract: The invention provides a method for inhibition of proliferation of primitive hematopoietic progenitor cells and hematopoietic stem cells, by incubating preparations containing said cells with IFN-.gamma.. The method is especially useful for protecting said cells during purging techniques using cytotoxic treatment, and for protection of said cells during in vivo cytotoxic treatment.
    Type: Grant
    Filed: August 14, 1995
    Date of Patent: September 15, 1998
    Assignee: Boehringer Mannheim GmbH
    Inventors: Zwi Berneman, Dirk Van Bockstaele, Hans-Willem Snoeck
  • Patent number: 5780301
    Abstract: Disclosed is a synthetic medium with PDGF, vitronectin, IL-1.beta. and BSA added to Eagle's minimum essential medium or medium with transferrin, insulin, progesterone and putrescine further added thereto. When cultivating the postnatal central neurons using the inventive medium, there are effects such that good attachment to substrate, extension of neuritic processes and maintenance of survival are achieved, that more stable sure cultivation becomes possible as well over the astrocyte-conditioned medium used hitherto, and the like.
    Type: Grant
    Filed: February 13, 1995
    Date of Patent: July 14, 1998
    Assignee: Kyorin Pharmaceutical Co., Ltd.
    Inventors: Hiroshi Saito, Hiroshi Katsuki, Fumio Kawahara
  • Patent number: 5766944
    Abstract: A procedure for carrying out T cell differentiation of CD34+ stem cells in an in vitro culture of thymic epithelial fragments whereby the differentiated T cells achieve full immunocompetence. The invention also includes the procedure for differentiation of stem cells from HIV seropositive individuals or genetically modified stem cells. The invention broadly relates to the culture of cultured thymic epithelial fragments and provides procedures for verifying true immunocompetence of the resulting T cells and for analyzing the effects of various compounds on the differentiation process. The invention also comprises several novel applications for utilizing the procedure of the invention, including grafting fortified cultured thymic epithelial fragments and infusing immunocompetent T cells into patients with compromised immune systems.
    Type: Grant
    Filed: December 31, 1996
    Date of Patent: June 16, 1998
    Inventor: Margaret Eileen Ruiz
  • Patent number: 5759856
    Abstract: Disclosed is a method for the culture of higher eukaryotic cells which are dependent for survival on an exogenous factor. The method involves co-culturing the factor-dependent cells with an immortalized eukaryotic cell that has been engineered to secrete the requisite factor.Also disclosed is a cell line of non-stromal cell origin which secretes interleukin-7.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: June 2, 1998
    Assignee: Benjamin E. Rich
    Inventors: Philip Leder, Benjamin E. Rich
  • Patent number: 5744361
    Abstract: The use of individual or combinations of cytokines, particularly IL-3, GM-CSF, and c-kit ligand are employed for long-term hematopoiesis in serum free culture in the absence of stromal cells. The cultures can be used for evaluating compounds and their effect on hematopoiesis, particularly as to lifetime and nature of differentiation. In addition, the expanded cells may be used for engraftment in a mammalian host or enhancement of particular cell lineages in a mammalian host. The subject systems may be used with any mammalian hemopoietic cells, but finds particular application with primates, more particularly humans.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: April 28, 1998
    Assignee: Indiana University
    Inventors: Ronald Hoffman, John Brandt
  • Patent number: 5705162
    Abstract: The present invention broadly relates to a therapeutic agent effective in mitigating disease associated with Feline Leukemia Virus (FeLV) in a feline infected with FeLV. A feline is an animal of the family Felidae. The novel therapeutic agent is composed of feline excised lymph nodes which have been subjected to mitogenic stimulation for their expansion dispersed in a pharmaceutically-acceptable carrier. Mitogenic stimulation conditions include culturing the excised lymph nodes in the presence of Interleukin-2. Optionally, culture conditions can include the presence of allogeneic or autologous FeLV tumor. The inventive therapeutic agent is prepared by excising lymph nodes from a feline infected the FeLV, mitogenically stimulating said excised lymph nodes for their expansion, and administering to the infected feline the expanded lymph nodes. Multidose regimens can be used as is necessary or desirable in convenient fashion.
    Type: Grant
    Filed: October 16, 1995
    Date of Patent: January 6, 1998
    Assignee: Parhelion Corporation
    Inventors: Richard G. Olsen, John L. Ridihalgh
  • Patent number: 5633162
    Abstract: A biochemically defined culture medium for culturing engineered Chinese hamster ovary (CHO) cell lines, which is essentially free from protein, lipid and carbohydrate isolated from an animal source, having water, an osmolality regulator, a buffer, an energy source, amino acids including L-glutamine, an inorganic or recombinant iron source, and a synthetic or recombinant growth factor, and optionally non-ferrous metal ions vitamins and cofactors. Also cells adapted to grow in such a culture medium.
    Type: Grant
    Filed: March 4, 1994
    Date of Patent: May 27, 1997
    Assignee: Glaxo Wellcome Inc.
    Inventors: Michael J. Keen, Nicholas T. Rapson
  • Patent number: 5610056
    Abstract: Stem cell factor in combination with interleukin-6 and soluble interleukin-6 receptor supports proliferation, differentiation and terminal maturation of erythroid cells from normal human hematopoietic stem cells.
    Type: Grant
    Filed: November 16, 1994
    Date of Patent: March 11, 1997
    Assignees: Amgen Inc., Tosoh Corporation
    Inventor: Tatsutoshi Nakahata