University of British Columbia

Centre for Drug Research and Development

Teva Pharmaceutical Industries Limited

Other

Martin E Gleave

Maxim Signaevsky

Eliana Beraldi

Paul Rennie

Colleen Nelson

Hideaki Miyake

Palma Rocchi

John K Jackson

Burkhard Jansen

Efstathios Gonos

Ioannis P Trougakos

Rajesh Kumar Kainthan

Donald Elliott Brooks

Jayachandran N Kizhakkedathu

Richard Tom Liggins

Dechi Guan

Helen M Burt

Alan So

Clement Mugabe

Lu Ye

Christopher J Ong

Michael N Pollak

Scott D Cormack

Claudia Kesch

Brett P Monia

James William Peacock

Tobias Zellweger

Amina Zoubeidi

Veronika Schmitt

Yuzhuo Wang

Randy J Levitt

Hikeaki Miyake

Kiyama Satoshi

Paul S Rennie

Randy J Leavitt

Joseph Ischia

Norihiro Hayashi

François Lamoureux

Masafumi Kumano

Colin C Collins

Peter Wilhelm Gout

Sze Ue Luk

Hui Xue

Gabriella Zupi

Efstathios S Gonos

Provided are methods, uses and pharmaceutical compositions for treatment of cancer with a B1SP fusion protein in a biologically effective amount sufficient to cause cell death of a prostate cancer cell or to inhibit proliferation of the prostate cancer cells. The cancer may be prostate cancer, breast cancer, ovarian cancer, bladder cancer, kidney cancer, glioblastoma or endometrial cancer. The prostate cancer may be an androgen receptor (AR) positive prostate cancer and the B1SP fusion protein may include asema domain, a structural stabilization domain; and a half life extending moiety.

B1SP fusion protein therapeutics, methods, and uses

This invention provides compositions for controlled localized depositing of one or more drugs within a subject. More particularly, described herein are compositions comprising a) a polyethylene glycol (PEG) composition having a first low molecular weight PEG (Mw between 200-500 Da) and a second low molecular weight PEG (Mw between 500-2000 Da) and b) a mucoadhesive in polymer. Alternatively, composition may comprise a) a polyethylene glycol (PEG) composition having a first low molecular weight PEG (Mw between 200-500 Da) and a second low molecular weight PEG (Mw between 500-2000 Da), b) a water insoluble polymer and c) a mucoadhesive polymer. Furthermore, the composition may further comprise one or more drugs. Also provided are methods of manufacturing and administering the compositions described herein, which are used as biodegradable, injectable mucoadhesive low-viscosity pastes.

Mucoadhesive polymeric drug delivery compositions and methods

This invention provides compositions for controlled localized release of one or more drugs within a subject. More particularly, described herein are compositions comprising a hydrophobic water-insoluble polymer, a low molecular weight biocompatible glycol, and one or more drugs. The compositions described herein may also optionally include a di-block copolymer and/or a swelling agent.

Polymeric paste compositions for drug delivery

Provided are methods, uses and pharmaceutical compositions for treatment of cancer with a B1SP fusion protein in a biologically effective amount sufficient to cause cell death of a prostate cancer cell or to inhibit proliferation of the prostate cancer cells. The cancer may be prostate cancer, breast cancer, ovarian cancer, bladder cancer, kidney cancer, glioblastoma or endometrial cancer. The prostate cancer may be an androgen receptor (AR) positive prostate cancer and the B1SP fusion protein may include a sema domain, a structural stabilization domain; and a half life extending moiety.

Herein are provided derivatized hyperbranched polyglycerols ('dHPGs'). The dHPG comprises a core comprising a hyperbranched polyglycerol derivatized with CCalkyl chains and a shell comprising at least one hydrophilic substituent bound to hydroxyl groups of the core, wherein the hyperbranched polyglycerol comprises from about 1 to about 200 moles of the at least one hydrophilic substituent. The dHPGs are for use as agents for the delivery of a drug or other biologically active moiety to the urinary tract, the digestive tract, the airways, the vaginal cavity and cervix and the peritoneal cavity to treat indications such as cancer, which may be useful in the treatment of or the manufacture of a medicament, in the preparation, of a pharmaceutical composition for the treatment of cancer, as a pre-treatment or co-treatment to improve drug uptake in a tissue. Furthermore, there are provided methods of making dHPGs.

Derivatized hyperbranched polyglycerols

Provided herein are compositions, method and uses for modulating IAP activity or for the treatment of cancer. The compositions comprise dual-targeting antisense oligonucleotides (dASO) for administration to a cancer cell, wherein the cancer cell may be characterized by elevated expression of one of more of BIRC6, cIAP1 or survivin. The cancer may be selected from one or more of: prostate cancer; childhood de novo acute myeloid leukemia; colorectal cancer; neuroblastoma; melanoma; and non-small cell lung cancer. The prostate cancer may be castration-resistant prostate cancer (CRPC).

Dual targeting antisense oligonucleotides as apoptotic inhibtor therapeutic compostions and methods for their use in the treatment of cancer

Combination therapy for cancer makes use of HSP27 inhibitors and EGFR tyrosine kinase inhibitors or etiolates.

Combination therapy for cancer using HSP27 inhibitor and EGFR tyrosine kinase inhibitors or anti-folates

Therapeutic agents which target heat shock protein (hsp) 27 in vivo are used to provide treatment to individuals, particularly human individuals, suffering from prostate cancer and other cancers that overexpress hsp27. A therapeutic agent, for example an antisense oligonucleotide or RNAi nucleotide inhibitor with sequence specificity for hsp27 mRNA, for example human hsp27 mRNA, is administered to an individual suffering from prostate cancer or some other cancer expressing elevated levels of hsp 27 in a therapeutically effective amount. The therapeutic agent is suitably formulated into a pharmaceutical composition which includes a pharmaceutically acceptable carrier, and packaged in dosage unit form. A preferred dosage unit form is an injectable dosage unit form.

Compositions and methods for treatment of prostate and other cancers

RNAi sequences that are useful as therapeutics in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease. These sequences target clusterin, IGFBP-5, IGFBP-2, both IGFBP-2 and -5 simultaneously, Mitf, and B-raf. The invention further provides for the use of these RNAi sequences in the treatment of cancers of various types, including prostate cancer, sarcomas such as osteosarcoma, renal cell carcinoma, breast cancer, bladder cancer, lung cancer, colon cancer, ovarian cancer, anaplastic large cell lymphoma and melanoma; and Alzheimer's disease, and a method of treating such conditions through the administration of the RNA molecules with RNAi activity to an individual, including a human individual in need of such treatment.

RNAi probes targeting cancer-related proteins

The present invention provides a method for treating a mammalian subject affected by prostate cancer comprising i) an oligonucleotide which reduces clusterin expression and ii) a Heat Shock Protein 90 (Hsp90) inhibitor each in an amount that when in combination with the other is effective to treat the mammalian subject. The present invention also provides pharmaceutical compositions comprising an amount of an oligonucleotide which reduces clusterin expression, and a Hsp90 inhibitor for use in treating a mammalian subject affected by prostate cancer. Also provided are oligonucleotides which reduce clusterin expression for use in combination with a Hsp90 inhibitor in treating a mammalian subject affected by prostate cancer, and a composition for treating a mammalian subject affected by prostate cancer comprising i) an oligonucleotide which reduces clusterin expression and ii) a Hsp90 inhibitor each in an amount that when in combination with the other is effective to treat the mammalian subject.

Combination of anti-clusterin oligonucleotide with Hsp90 inhibitor for the treatment of prostate cancer

Castrate resistant prostate cancer cell lines exhibiting resistance to the androgen-receptor antagonist enzaluatamide overexpress one or both of IGFBP-2 or IGFBP-5 when compared to non-resistant cell lines. Oligonucleotides that target IGFBP-2 and IGFBP-5 can be used to overcome this resistance or as part of a treatment program when administered concurrently with the administration of androgen-receptor antagonist treatments.

Method for treatment of castration-resistant prostate cancer

A method for providing antisense therapy which reduces the expression of clusterin to provide therapeutic benefits in the treatment of cancer comprising administering from 40 to 640 mg anti-clusterin antisense oligonucleotide to a patient in need of treatment for a cancer expressing clusterin is provided. The method may include administering chemotherapeutic agent or agents, radiotherapy, and/or hormone ablation therapy. The invention also encompasses pharmaceutical compositions formulated to provide a dosage of 40 to 640 mg, and use of antisense in formulating a medicament.

Clusterin antisense therapy for treatment of cancer

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Vancouver, Canada

Martin E Gleave