Menlo Park, CA, United States
Menlo Park, CA, United States

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Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having ET.


Patent
Geron | Date: 2015-08-06

The present disclosure relates to RNA amidates and thioamidates useful for RNA interference applications. The RNA amidates and thioamidates contain at least one internucleoside linkage chosen from ribo-N3P5 phosphoramidate (NP) and ribo-N3P5 thiophosphoramidate (NPS) linkages, and optionally further containing at least one covalently conjugated lipid moiety. Compositions comprising the amidates and thioamidates are disclosed, as are methods for their use in modulating gene expression.


Patent
Geron | Date: 2016-05-16

Orthogonally protected 3-amino nucleoside monomers and efficient methods for their synthesis are described. The methods employ selective protection of the 3-amino group in the presence of the unprotected nucleoside base.


Provided herein are methods for identifying individuals diagnosed with a cell proliferative disorder that will benefit from treatment with a telomerase inhibitor compound. Also provided herein are methods for treating these individuals with telomerase inhibitor compounds.


Patent
Geron | Date: 2015-05-18

Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.


Patent
Geron | Date: 2015-06-02

Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.


A method and kit for inhibiting the proliferation of cancer cells are disclosed, based on a combination of a gemcitabine and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with gemcitabine alone or the telomerase inhibitor alone. Preferably, efficacy is supraadditive or synergistic in nature relative to the combined effects of the individual agents, with minimal exacerbation of side effects.


A method and kit for inhibiting the proliferation of carcinoma cells are disclosed, based on a combination of an EGF pathway inhibitor and a telomerase inhibitor. When used in cancer therapy, the two compounds in combination enhance the anti-cancer treatment efficacy obtained with the antibody alone or the telomerase inhibitor alone.


Aspects of the disclosure include methods for the preparation of a polynucleotide. In some embodiments, the method includes contacting a first polynucleotide composition including: a polynucleotide having a sequence of 7 or more nucleoside subunits and at least two of the nucleoside subunits are joined by a N3P5 thiophosphoramidate inter-subunit linkage; and non-target synthetic products and reagents; with a multivalent cation salt to precipitate a polynucleotide salt including at least one multivalent cation counterion; and separating the polynucleotide salt from the contacted first polynucleotide composition to produce a second polynucleotide composition including the polynucleotide salt. In certain embodiments, the method further includes contacting the polynucleotide salt with a reverse phase chromatography support; and eluting from the chromatography support a third polynucleotide composition including the polynucleotide. Also provided are compositions including a salt of the polynucleotide including at least one multivalent cation counterion.


The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.

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