Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N-x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N-x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: 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 N3??P5? 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.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: 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 N3??P5? 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.

Abstract: 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 N3??P5? 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.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and for enhancing proliferation of stem and progenitor cells.

Abstract: The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and for enhancing proliferation of stem and progenitor cells.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and for enhancing proliferation of stem and progenitor cells.

Abstract: 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 N3??P5? 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.

Abstract: The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and for enhancing proliferation of stem and progenitor cells.

Abstract: The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3?-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3??P5? phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3? amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3? amino group; (b) contacting the free 3? amino group with a 3?-protected amino-dinucleotide-5?-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3??P5? phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N?x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.

Abstract: The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and for enhancing proliferation of stem and progenitor cells.

Abstract: A process for the preparation of neuraminidase inhibitors having structural formula (28) 1