Abstract: The disclosure relates to oligonucleotide compounds (oligomers) that target Myc mRNA in a cell, leading to reduced expression of Myc. Reduction of Myc expression is beneficial for the treatment of certain disorders, such as hyperproliferative disorders (e.g., cancer). The disclosure provides therapeutic compositions comprising oligomers and methods for modulating the expression of Myc using said oligomers, including methods of treatment.
Type:
Grant
Filed:
February 15, 2013
Date of Patent:
November 29, 2016
Assignees:
DANA-FARBER CANCER INSTITUTE, INC., ENZON PHARMACEUTICALS, INC.
Inventors:
Rajanikanth Bandaru, Yixian Zhang, Zhengxing Qu, Lee Greenberger, Christopher Ott, James Elliott Bradner
Abstract: The invention provides the combination use of antisense oligomers targeting androgen receptor mRNA and androgen receptor binding inhibitors that reduce androgen receptor activity for the treatment of androgen receptor related medical disorders, such as cancers, particularly prostate cancers and breast cancers.
Abstract: Oligonucleotides directed against the hypoxia-inducible factor-1? (HIF-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.
Type:
Application
Filed:
December 21, 2012
Publication date:
May 9, 2013
Applicants:
Santaris Pharma A/S, Enzon Pharmaceuticals, Inc.
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 neighboring nucleotides/LNA nucleotide analogues, and subscript “x” designates either a phosphorothioate link or a phosphorodiester link between neighboring 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.
Type:
Grant
Filed:
April 4, 2011
Date of Patent:
April 2, 2013
Assignees:
Santaris Pharma a/s, Enzon Pharmaceuticals, Inc.
Inventors:
Majken Westergaard, Charlotte Albaek Thrue, Frank Winther Rasmussen, Henrik Frydenlund Hansen
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.
Type:
Grant
Filed:
March 12, 2009
Date of Patent:
February 5, 2013
Assignee:
Enzon Pharmaceuticals, Inc.
Inventors:
Hong Zhao, Prasanna Reddy, Maria Belen Rubio
Abstract: Oligonucleotides directed against the hypoxia-inducible factor-1? (HIF-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 relates to polymeric conjugates of adenine nucleoside analogs. In particular, the invention relates to multi-arm polyethylene glycol conjugates of adenine nucleoside analogs and use thereof. The present invention, more specifically, provides polymeric conjugates of toyocamycin and its derivatives. Furthermore, the present invention provides a method for preparing the polymeric conjugates of adenine nucleoside analogs and a method of using the same for treating a cancer, inhibiting the growth or proliferation of cancer cells, treating a viral infection, treating a disease or condition associated with abnormal expression of VEGF. Most polymeric conjugates of toyocamycin was stable in PBS but released toyocamycin in vivo to provided inhibition of cancer cell growth.
Abstract: The invention relates to oligomer compounds (oligomers), which target HER3 mRNA in a cell, leading to reduced expression of HER3 and/or HER2 and/or EGFR. Reduction of HER3 and/or HER2 and/or EGFR expression is beneficial for a range of medical disorders, such hyperproliferative disorders (e.g., cancer). The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of HER3 and/or HER2 and/or EGFR using said oligomers, including methods of treatment.
Type:
Application
Filed:
June 22, 2012
Publication date:
November 22, 2012
Applicants:
Santaris Pharma A/S, Enzon Pharmaceuticals, Inc.
Abstract: The present invention relates to releasable urea linker systems involving amine-containing chemical compounds and biologically active agents. In particular, the present invention relates to reversibly releasable linkers based on intramolecular cyclization-assisted releasable urea linkages to aromatic amine-containing compounds. The present invention also relates to polymeric conjugates of indolinone-based tyrosine kinase inhibitors.
Type:
Application
Filed:
December 30, 2010
Publication date:
November 15, 2012
Applicant:
ENZON PHARMACEUTICALS, INC.
Inventors:
Hong Zhao, Dechun Wu, Snehlata Tripathi, Jing Xia
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.
Type:
Grant
Filed:
April 19, 2010
Date of Patent:
October 30, 2012
Assignee:
Enzon Pharmaceuticals, Inc.
Inventors:
Hong Zhao, Maria Belen Rubio, Dechun Wu, Puja Sapra
Abstract: Oligonucleotides directed against the hypoxia-inducible factor-1? (HIF-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.
Type:
Application
Filed:
May 22, 2012
Publication date:
October 25, 2012
Applicants:
Santaris Pharma A/S, Enzon Pharmaceuticals. Inc.
Inventors:
Charlotte Albæk Thrue, Anja Mølhart Høg, Paul E.G. Kristjansen
Abstract: The present invention provides polymeric delivery systems including hindered ester moieties. Methods of making the polymeric delivery systems and methods of treating mammals using the same are also disclosed.
Abstract: The invention relates to oligomer compounds (oligomers), which target HER3 mRNA in a cell, leading to reduced expression of HER3 and/or HER2 and/or EGFR. Reduction of HER3 and/or HER2 and/or EGFR expression is beneficial for a range of medical disorders, such hyperproliferative disorders (e.g., cancer). The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of HER3 and/or HER2 and/or EGFR using said oligomers, including methods of treatment.
Type:
Grant
Filed:
May 9, 2008
Date of Patent:
September 18, 2012
Assignees:
Santaris Pharma A/S, Enzon Pharmaceuticals, Inc.
Abstract: The present invention relates to methods of treating a HER2 positive cancer in mammals. The present invention includes administering a HER2 antagonist in combination with a polymeric prodrug of 7-ethyl-10-hydroxycamptothecin to the mammals in need thereof.
Abstract: Oligonucleotides directed against the hypoxia-inducible factor-1? (HIF-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.
Type:
Grant
Filed:
October 27, 2010
Date of Patent:
June 26, 2012
Assignees:
Santaris Pharma A/S, Enzon Pharmaceuticals, Inc.
Inventors:
Charlotte Albaek Thrue, Anja Molhart Hog, Paul E. G. Kristjansen
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.
Type:
Grant
Filed:
July 25, 2008
Date of Patent:
June 5, 2012
Assignee:
Enzon Pharmaceuticals, Inc.
Inventors:
Hong Zhao, Richard B. Greenwald, Susan L. Adler, legal representative
Abstract: The present invention relates to methods of inhibiting angiogenesis in mammals. The present invention includes administering polymeric prodrugs of 7-ethyl-10-hydroxycamptothecin to the mammals in need thereof. The present invention also relates to methods of treating a disease associated with angiogenesis in mammals by administering polymeric prodrugs of 7-ethyl-10-hydroxycamptothecin to the mammals in need thereof.
Abstract: The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5?-(MeCx)(Tx)MeCxAsAstscscsastsgsgsMeCxAx(Gx)(c)-3?, and preferably of the general formula 5?-MeCxTxMeCxAsastscscsastsgsgsMeCxAxGxc-3?, wherein capital letters designate an LNA nucleotide analogue selected from ?-D-oxy-LNA, ?-D-thio-LNA, ?-D-amino-LNA and ?-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumor development in vivo.
Type:
Grant
Filed:
October 10, 2008
Date of Patent:
May 8, 2012
Assignees:
Santaris Pharma A/S, Enzon Pharmaceuticals, Inc.
Inventors:
Christoph Rosenbohm, Lene Sonderbye Kjaerulff, Majken Westergaard, Margit Wissenbach, Jens Bo Hansen, Marlene Asklund
Abstract: One aspect of the invention provides methods for treating cancers which are resistant to treatment with a protein tyrosine kinase inhibitor by co-treatment with the protein tyrosine kinase inhibitor and one or more antisense oligomers that reduce the expression of HER3 and/or HER2 and/or EGFR. Another aspect of the invention provides methods for treating cancers by co-treatment with an inhibitor of HER2 and one or more antisense oligomers that reduce the expression of HER3.
Type:
Application
Filed:
April 14, 2010
Publication date:
March 29, 2012
Applicants:
ENZON PHARMACEUTICALS, INC.
Inventors:
Yixian Zhang, Zhengxing Qu, Lee Martin Greenberger