Abstract: The present invention relates to oligomer compounds (oligomers), which target GLI2 mRNA in a cell, leading to reduced expression of GLI2. Reduction of GLI2 expression is beneficial for the treatment of certain medical disorders, such as hyperproliferative disorders, such as cancer.

Abstract: The present invention is directed to nanoparticle compositions for the delivery of oligonucleotides and methods of modulating an expression of a targeted gene using the nanoparticle compositions. In particular, the invention relates to oligonucleotides encapsulated in a mixture of a cationic lipid, a fusogenic lipid and a PEG lipid.

Abstract: The present disclosure relates to an LNA oligonucleotide consisting of a sequence selected from the group consisting of 5?-(Tx)GxGxcsasasgscsastscscsTxGxT-3? and 5?-(Gx)TxTxascstsgscscststscsTxTxA-3?, wherein capital letters designate a beta-D-oxy-LNA nucleotide analogue, small letters designate a 2-deoxynucleotide, underline designates either a beta-D-oxy-LNA nucleotide analogue or a 2-deoxynucleotide, subscript “s” designates a phosphorothioate link between neighbouring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighbouring nucleotides/LNA nucleotide analogues, and wherein the sequence is optionally extended by up to five 2-deoxynucleotide units. The LNA oligonucleotides are useful for modulating the expression of hypoxia-inducible factor-1a (HIF-1a), e.g. in the treatment of cancer diseases, inhibiting angiogenesis, inducing apoptosis, preventing cellular proliferation, or treating an angiogenic disease, e.g.

Abstract: The present invention provides polymeric prodrugs including an intracellular releasable disulfide linker for the delivery of oligonucleotides. Methods of making the compounds as well as methods of delivering nucleic acids to tumor cells in a mammal using the same are also provided.

Abstract: A method of treating a resistant or refractory cancer in a mammal includes administering an effective amount of a compound of to the mammal. In preferred aspects, the cancer is resistant or refractory to CPT-11 or CPT therapy.

Abstract: The invention relates to oligomer compounds (oligomers), which target beta-catenin mRNA in a cell, leading to reduced expression of beta-catenin. Reduction of beta-catenin expression is beneficial for a range of medical disorders, such as hyperproliferative disorders, such as cancer. The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of beta-catenin using said oligomers, including methods of treatment.

Abstract: The invention relates to oligomeric compounds (oligomers), which target PIK3CA mRNA in a cell, leading to reduced expression of PIK3CA. Reduction of PIK3CA expression is beneficial for the treatment of certain medical disorders, such as hyperproliferative diseases (e.g., cancer). The invention provides therapeutic compositions that include the oligomers and methods for modulating the expression of PIK3CA using the oligomers, including methods of treatment.

Abstract: The invention relates to oligomer compounds (oligomers), which target beta-catenin mRNA in a cell, leading to reduced expression of beta-catenin. Reduction of beta-catenin expression is beneficial for a range of medical disorders, such as hyperproliferative disorders, such as cancer. The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of beta-catenin using said oligomers, including methods of treatment.

Abstract: Activated polymeric bicine derivatives such as as well as conjugates made therewith are disclosed. Methods of making and using the bicine derivatives are also disclosed.

Abstract: The present invention is directed to methods of preparing linear polymers such as polyalkylene oxides containing a terminal amine in high purity. One preferred method includes reacting a polyalkylene oxide such as polyethylene glycol containing a terminal azide with a phosphine-based reducing agent such as triphenylphosphine or an alkali metal borohydride reducing agent such as sodium borohydride in a solvent to reflux. The resultant polymer-amines are of sufficient purity so that expensive and time consuming purification steps required for pharmaceutical grade polymers are avoided.

Abstract: The invention relates to oligomeric compounds (oligomers), which target PIK3CA mRNA in a cell, leading to reduced expression of PIK3CA. Reduction of PIK3CA expression is beneficial for the treatment of certain medical disorders, such as hyperproliferative diseases (e.g., cancer). The invention provides therapeutic compositions that include the oligomers and methods for modulating the expression of PIK3CA using said oligomers, including methods of treatment.

Abstract: Oligonucleotides directed against the hypoxia-inducible factor-1? (HIP-1?) gene are provided for modulating the expression of HIF-1?. The compositions comprise oligonucleotides, particularly antisense oligonucleotides, targeted to nucleic acids encoding the HIF-1?. Methods of using these compounds for modulation of HIF-1? expression and for the treatment of diseases associated with the hypoxia-inducible factor-1? are provided. Examples of diseases are cancer and pre-eclampsia. The oligonucleotides may be composed of deoxyribonucleosides, a nucleic acid analogue, or Locked Nucleic Acid (LNA) or a combination thereof.

Abstract: The present invention provides polymeric siRNA conjugates. Methods for down-regulation of gene expression in vivo and in vitro and for inhibition of the growth of cancer cells using the conjugates are also disclosed.

Abstract: The invention relates to oligonucleotide compounds (oligomers), which target androgen receptor mRNA in a cell, leading to reduced expression of the androgen receptor. Reduction of the androgen receptor expression is beneficial for the treatment of certain disorders, such as a hyperproliferative disorders (e.g., cancer). The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of androgen receptor using said oligomers, including methods of treatment.

Abstract: The invention provides hindered ester-based biodegradable linkers for the delivery of oligonucleotides in vivo, as well as method of making and using the same.

Abstract: The present invention provides single chain antibody-directed polymeric prodrugs containing multifunctional linkers. Methods of making the polymeric delivery systems and methods of treating mammals using the same are also disclosed.

Abstract: A four arm-polyethylene glycol-7-ethyl-10-hydroxycamptothecin conjugate, such as, is disclosed. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.

Abstract: The present invention provides polymeric linkers containing pyridyl disulfide moieties. Methods of making the polymeric linkers and methods of making conjugates using the same are also disclosed.

Abstract: The present invention relates to methods of treatment of non-Hodgkin's lymphomas. The present invention includes administering polymeric prodrugs of 7-ethyl-10-hydroxycamptothecin to patients in need thereof.

Abstract: A four arm-polyethylene glycol-7-ethyl-10-hydroxycamptothecin conjugate, such as, is disclosed. Methods of making the conjugates and methods of treating mammals using the same are also disclosed.