# US 8,772,470 B1 · Compositions and methods for treatment of prostate and other cancers

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- Number: US 8,772,470 B1
- Document ID: US8772470B1
- Status: Granted
- Kind: B1
- Application number: 11/948,195
- Filed: 2007-11-30
- Granted: 2014-07-08
- Earliest claimed: 2002-10-02
- Assignees: The University of British Columbia
- Applicants: Martin Gleave; Palma Rocchi; Maxim Signaevsky; Eliana Beraldi
- Inventors: Martin Gleave; Palma Rocchi; Maxim Signaevsky; Eliana Beraldi
- Web page: https://patentgrep.com/patent/US8772470B1

## CPC

- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/7125: Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 2310/11: Antisense
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/315: Phosphorothioates
- C12N 2320/30: Special therapeutic applications
- C12N 2320/31: Combination therapy
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

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.

## Claims

### Claim 1

A pharmaceutical composition comprising a therapeutic agent effective to reduce the amount of active hsp27 in cancerous cells exposed to the therapeutic agent, and a pharmaceutically acceptable carrier, wherein the therapeutic agent comprises an RNAi molecule, wherein said RNAi molecule is from 18 to 23 nucleotides and comprises double-stranded or single-stranded RNA and mediates RNA inhibition by degradation of mRNA of the hsp27 gene and; wherein said RNAi molecule consists of a single-stranded sequence or two complementary sequences in a double stranded form that is/are the RNA counterpart of sequence of bases of the same length as the RNAi molecule within Seq ID No. 91 or complementary to Seq. ID No. 91, wherein the RNAi molecule has backbone modifications to provide resistance against nuclease digestion in vivo.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the RNAi molecule comprises the sequence of bases as set forth in any of Seq. ID No. 83-90.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the RNAi molecule comprises the sequence of bases as set forth in Seq. ID No. 84.

### Claim 4 (depends on 3)

The composition of claim 3, wherein the composition is packaged in dosage unit form.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the dosage unit form is an injectable solution.

### Claim 6 (depends on 2)

The composition of claim 2, wherein the composition is packaged in dosage unit form.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the dosage unit form is an injectable solution.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the composition is packaged in dosage unit form.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the dosage unit form is an injectable solution.

### Claim 10 (depends on 1)

The composition of claim 1, wherein said RNAi molecule consists of a single stranded sequence or two complementary sequences in a double stranded form that is/are the RNA counterpart of sequence of bases of the same length as the RNAi molecule within Seq ID No. 91 and/or is complementary to a series of bases selected from the group consisting of bases 131-161, 241-261, 361-371, 551-580, 661-681 and 744-764.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the composition is packaged in dosage unit form.

### Claim 12 (depends on 11)

The composition of claim 11, wherein the dosage unit form is an injectable solution.

### Claim 13 (depends on 10)

The composition of claim 10, wherein said RNAi molecule consists of a sequence that is the same as or is complementary to bases 361-371.

### Claim 14 (depends on 13)

The composition of claim 13, wherein the RNAi molecule comprises the sequence of bases as set forth in the SEQ ID No: 85.

### Claim 15 (depends on 10)

The composition of claim 10, wherein said RNAi molecule consists of a sequence that is the same as or is complementary to bases 551-580.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the RNAi molecule comprises the sequence of bases as set forth in the SEQ ID No: 87.

### Claim 17 (depends on 15)

The composition of claim 15, wherein the RNAi molecule comprises the sequence of bases as set forth in the SEQ ID No: 88.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the RNAi molecule is 19 nucleotides in length.

### Claim 19

A pharmaceutical composition comprising a therapeutic agent effective to reduce the amount of active hsp27 in cancerous cells exposed to the therapeutic agent, and a pharmaceutically acceptable carrier, wherein the therapeutic agent comprises an RNAi molecule, wherein said RNAi molecule is a double-stranded RNA formed from two RNA strands in which each strand is from 18 to 23 nucleotides, and wherein a first of the strands is complementary to a sequence of bases within SEQ ID NO: 91 that is of the same length as the first strand and a second strand is complementary to the first strand.

### Claim 20 (depends on 19)

The composition of claim 19, wherein said first strand of the RNAi molecule is complementary to a series of bases within SEQ ID NO: 91 selected from the group consisting of bases 131-161, 241-261, 361-371, 551-580, 661-681 and 744-764.

### Claim 21 (depends on 19)

The composition of claim 19 , wherein the first strand of the RNAi molecule comprises the sequence of bases as set forth in any of Seq. ID No. 83-90.

### Claim 22 (depends on 19)

The composition of claim 19 , wherein the first strand of the RNAi molecule comprises the sequence of bases as set forth in Seq. ID No. 84.

### Claim 23 (depends on 20)

The composition of claim 20, wherein the first strand of said RNAi molecule consists of a sequence that is the same as or is complementary to bases 361-371.

### Claim 24 (depends on 23)

The composition of claim 23, wherein the first strand of the RNAi molecule comprises the sequence of bases as set forth in the SEQ ID No: 85.

### Claim 25 (depends on 23)

The composition of claim 23, wherein the first strand of said RNAi molecule consists of a sequence that is the same as or is complementary to bases 551-580.

### Claim 26 (depends on 25)

The composition of claim 25, wherein the first strand of the RNAi molecule comprises the sequence of bases as set forth in the SEQ ID No: 87.

### Claim 27 (depends on 25)

The composition of claim 25, wherein the first strand of the RNAi molecule comprises the sequence of bases as set forth in the SEQ ID No: 88.
