Abstract: This disclosure provides a system for qualifying embryonic stem cells intended for human therapy. A large-scale sequencing project has identified important markers that are characteristic of undifferentiated pluripotent cells. Combinations of these markers can be used to validate the self-renewing capacity of ES cells, and their ability to differentiate into tissue types suitable for regenerative medicine. The marker system of this invention has been used to screen feeder cells, media additives, and culture conditions that promote proliferation of stem cells without differentiation. A culture system optimized by following these markers is suitable for rapid expansion of undifferentiated cells from existing lines, or the derivation of new lines that are equally apposite for clinical use.
Type:
Grant
Filed:
March 13, 2003
Date of Patent:
December 26, 2006
Assignee:
Geron Corporation
Inventors:
Lawrence W. Stanton, Ralph Brandenberger, Joseph D. Gold, John M. Irving, Ramkumar Mandalam, Michael Mok
Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one internucleoside 3?-NHP(O)(S?)O-5? linkage, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive thiophosphoramidate oligonucleotides were found to retain the high RNA binding affinity of the parent oligonucleotide N3??P5? phosphoramidates and to exhibit a much higher acid stability.
Type:
Grant
Filed:
October 18, 2004
Date of Patent:
November 21, 2006
Assignee:
Geron Corporation
Inventors:
Sergei Gryaznov, Krisztina Pongracz, Tracy Matray
Abstract: This disclosure provides a system for generating animal tissue with carbohydrate antigens that are compatible for transplantation into human patients. The tissue is inactivated homozygously for expression of ?(1,3)galactosyltransferase, and comprises a transgene for ?(1,2)fucosyltransferase. As a result, cell-surface N-acetyl lactosamine is not converted to the Gal?(1,3)Gal xenoantigen. Instead, it is converted to Fuc?(1,2)Gal, which is H substance, a self-antigen in humans. The tissue may also contain A or B-transferase, which will cause H substance to be converted into other ABO blood group antigens for compatibility with patients of the same blood type. This invention improves transplant compatibility of the xenograft tissue by lessening the risk of reactions resulting from xenoantigen and unconverted N-acetyl lactosamine acceptor determinants.
Type:
Grant
Filed:
March 21, 2002
Date of Patent:
October 24, 2006
Assignee:
Geron Corporation
Inventors:
Chris Denning, A. John Clark, J. Michael Schiff
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. Catalytically active and inactive human telomerase reverse transcriptase variants comprising deletions or other mutations are provided.
Abstract: This invention provides purified telomerase and methods of purifying it. The methods involve the use of several sequential steps, including the use of matrices that bind molecules bearing negative charges, matrices that bind molecules bearing positive charges, intermediate-selectivity matrices, methods that separate molecules based on their size, shape, or buoyant density, and by affinity purification.
Type:
Grant
Filed:
March 26, 2004
Date of Patent:
June 27, 2006
Assignee:
Geron Corporation
Inventors:
Scott L. Weinrich, Edward M. Atkinson, III, Serge P. Lichtsteiner, Alain P. Vasserot, Ronald A. Pruzan
Abstract: The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.
Type:
Grant
Filed:
April 26, 2001
Date of Patent:
June 6, 2006
Assignees:
Geron Corporation, Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: This disclosure provides an improved system for culturing human pluripotent stem (pPS) cells in the absence of feeder cells. The role of the feeder cells can be replaced by supporting the culture on an extracellular matrix, and culturing the cells in a conditioned medium. Permanent cell lines are provided that can produce conditioned medium on a commercial scale. Methods have also been discovered to genetically alter pPS cells by introducing the cells with a viral vector or DNA/lipid complex. The system described in this disclosure allows for bulk proliferation of pPS cells for use in studying the biology of pPS cell differentiation, and the production of important products for use in human therapy.
Type:
Grant
Filed:
October 23, 2001
Date of Patent:
May 9, 2006
Assignee:
Geron Corporation
Inventors:
Melissa K. Carpenter, Margaret S. Inokuma, Chunhui Xu
Abstract: This disclosure provides a system for producing pancreatic islet cells from embryonic stem cells. Differentiation is initiated towards endoderm cells, and focused using reagents that promote emergence of islet precursors and mature insulin-secreting cells. High quality populations of islet cells can be produced in commercial quantities for use in research, drug screening, or regenerative medicine.
Abstract: The present invention is directed to methods of identifying in a sample nucleic acids that encode human telomerase reverse transcriptase (hTRT) or its fragments. The present invention is also directed to oligonucleotide primers used in such methods. The invention is further directed to PCR products that hybridize under stringent conditions to a polynucleotide encoding hTRT, as well as hybridization complexes comprising one strand of a cellular hTRT nucleic acid and one strand of nucleic acid comprising a recombinant or synthetic fragment of hTRT.
Type:
Grant
Filed:
January 18, 2002
Date of Patent:
February 28, 2006
Assignees:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Type:
Application
Filed:
August 17, 2005
Publication date:
February 23, 2006
Applicants:
Geron Corporation, The Regents of the University of Colorado
Inventors:
Thomas Cech, Joachim Lingner, Toru Nakamura, Karen Chapman, Gregg Morin, Calvin Harley, William Andrews
Abstract: This disclosure provides a system for minimizing the alloreactivity of tissue transplants. The patient is administered with undifferentiated embryonic stem cells or early progenitor cells. This induces a state of inflammatory quiescence or immune unresponsiveness, which in turn enhances engraftment of cells derived from the same stem cell line given for purposes of regenerative medicine.
Type:
Application
Filed:
September 24, 2004
Publication date:
December 22, 2005
Applicants:
The Robarts Research Institute, Geron Corporation
Abstract: A method of inhibiting the self-splicing of a Group I intron is disclosed. The method uses an oligonucleotide having a sequence essentially identical to a guide sequence found in the 5? flanking exon and terminates with a 3? ribonucleoside. Usually the oligonucleotide has N3??P5? phosphoramidate or N3??P5? thiophiosphoramidate linkages rather than phosphodiester linkages. A method of inhibiting the growth of organisms having Group I intron, particularly certain pathogenic fungi including P. carinii, C. albicans, and A. nidulans using the oglionucleotide is also provided.
Type:
Grant
Filed:
March 15, 2000
Date of Patent:
October 25, 2005
Assignees:
Geron Corporation, The University of Rochester
Inventors:
Stephen M. Testa, Matthew D. Disney, Sergei M. Gryaznov, Douglas H. Turner
Abstract: The present invention is directed to novel telomerase nucleic acids and amino acids. In particular, the present invention is directed to nucleic acid and amino acid sequences encoding various telomerase protein subunits and motifs, including the 123 kDa and 43 kDa telomerase protein subunits of Euplotes aediculatus, and related sequences from Schizosaccharomyces, Saccharomyces sequences, and human telomerase. The present invention is also directed to polypeptides comprising these telomerase protein subunits, as well as functional polypeptides and ribonucleoproteins that contain these subunits.
Type:
Grant
Filed:
November 12, 1999
Date of Patent:
August 9, 2005
Assignees:
Geron Corporation, University Technology Corporation
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: The present invention is directed to expression vectors comprising a polynucleotide that encodes a human telomerase reverse transcriptase (hTRT) protein, variant, or fragment. The present invention is also directed to host cells that comprise expression vectors comprising a polynucleotide that encodes a hTRT protein variant, or fragment.
Type:
Grant
Filed:
January 18, 2002
Date of Patent:
July 26, 2005
Assignees:
Regents of the University of Colorado, Geron Corporation
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: This invention provides a system for producing differentiated cells from a stem cell population for use wherever a relatively homogenous cell population is desirable. The cells contain an effector gene under control of a transcriptional control element (such as the TERT promoter) that causes the gene to be expressed in relatively undifferentiated cells in the population. Expression of the effector gene results in expression of a cell-surface antigen that can be used to deplete the undifferentiated cells. Model effector sequences encode glycosyl transferases that synthesize carbohydrate xenoantigen or alloantigen, which can be used for immunoseparation or as a target for complement-mediated lysis. The differentiated cell populations produced are suitable for use in tissue regeneration and non-therapeutic applications such as drug screening.
Type:
Grant
Filed:
November 26, 2001
Date of Patent:
July 26, 2005
Assignees:
Roslin Institute (Edinburgh), Geron Corporation
Inventors:
Jim McWhir, Joseph D. Gold, J. Michael Schiff
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Type:
Application
Filed:
June 24, 2004
Publication date:
January 20, 2005
Applicants:
GERON CORPORATION, UNIVERSITY TECHNOLOGY CORPORATION
Inventors:
Thomas Cech, Joachim Lingner, Toru Nakamura, Karen Chapman, Gregg Morin, Calvin Harley, William Andrews
Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one internucleoside 3′-NHP(O)(S−)O-5′ linkage, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive thiophosphoramidate oligonucleotides were found to retain the high RNA binding affinity of the parent oligonucleotide N3′→P5′ phosphoramidates and to exhibit a much higher acid stability.
Type:
Grant
Filed:
June 17, 2003
Date of Patent:
December 28, 2004
Assignee:
Geron Corporation
Inventors:
Sergei Gryaznov, Krisztina Pongracz, Tracy Matray
Abstract: This invention provides populations of neural progenitor cells, differentiated neurons, glial cells, and astrocytes. The populations are obtained by culturing stem cell populations (such as embryonic stem cells) in a cocktail of growth conditions that initiates differentiation, and establishes the neural progenitor population. The progenitors can be further differentiated in culture into a variety of different neural phenotypes, including dopaminergic neurons. The differentiated cell populations or the neural progenitors can be generated in large quantities for use in drug screening and the treatment of neurological disorders.
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Type:
Application
Filed:
June 24, 2004
Publication date:
December 9, 2004
Applicants:
GERON CORPORATION, UNIVERSITY TECHNOLOGY CORPORATION
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews
Abstract: The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. The polynucleotides and polypeptides of the invention are useful for diagnosis, prognosis and treatment of human diseases, for changing the proliferative capacity of cells and organisms, and for identification and screening of compounds and treatments useful for treatment of diseases such as cancers.
Type:
Application
Filed:
June 24, 2004
Publication date:
December 2, 2004
Applicants:
GERON CORPORATION, UNIVERSITY TECHNOLOGY CORPORATION
Inventors:
Thomas R. Cech, Joachim Lingner, Toru Nakamura, Karen B. Chapman, Gregg B. Morin, Calvin B. Harley, William H. Andrews