Compound and method for treating androgen-independent prostate cancer
First Claim
1. A method of treating prostate cancer in a subject having an androgen-independent prostate cancer, as evidenced by a lack of response in PSA level to androgen-suppression therapy, said method comprising (a) administering to the subject, an oligonucleotide analog compound characterized by:
- (i) 12-40 morpholino subunits, (ii) a substantially uncharged, phosphorus-containing backbone linking said subunits, (iii) active uptake by human prostate cancer cells, (iv) a base sequence that is complementary to a target region containing at least 12 contiguous bases in a preprocessed or processed human androgen receptor transcript, and which includes at least 6 contiguous bases of the sequence selected from the group consisting of;
SEQ ID NOS;
2, 7, 8, and 9-22, and (v) capable of hybridizing with a preprocessed human androgen-receptor transcript to form a heteroduplex structure having a Tm of dissociation of at least 45°
C., (c) following said administering, monitoring the subject'"'"'s serum PSA level, and (d) continuing said administering, on a periodic basis, at least until a substantial drop in the subject'"'"'s serum PSA level is observed.
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Accused Products
Abstract
The present invention provides compositions and methods for treating prostate cancer. The composition comprises a morpholino antisense compound having uncharged phosphorus-containing backbone linkages and a base sequence that is complementary to a target region containing at least 12 contiguous bases in a preprocessed or processed human androgen receptor transcript. The method is designed for treating prostate cancer in a subject having a hormone-refractory (androgen-independent) prostate cancer.
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Citations
22 Claims
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1. A method of treating prostate cancer in a subject having an androgen-independent prostate cancer, as evidenced by a lack of response in PSA level to androgen-suppression therapy, said method comprising
(a) administering to the subject, an oligonucleotide analog compound characterized by: -
(i) 12-40 morpholino subunits, (ii) a substantially uncharged, phosphorus-containing backbone linking said subunits, (iii) active uptake by human prostate cancer cells, (iv) a base sequence that is complementary to a target region containing at least 12 contiguous bases in a preprocessed or processed human androgen receptor transcript, and which includes at least 6 contiguous bases of the sequence selected from the group consisting of;
SEQ ID NOS;
2, 7, 8, and 9-22, and(v) capable of hybridizing with a preprocessed human androgen-receptor transcript to form a heteroduplex structure having a Tm of dissociation of at least 45°
C.,(c) following said administering, monitoring the subject'"'"'s serum PSA level, and (d) continuing said administering, on a periodic basis, at least until a substantial drop in the subject'"'"'s serum PSA level is observed. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. An oligonucleotide analog compound for use in treating prostate cancer in a subject, characterized by:
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(i) 12-40 morpholino subunits, (ii) a substantially uncharged, phosphorus-containing backbone linking said subunits, (iii) active uptake by human prostate cancer cells, (iv) a base sequence that is complementary to a target region containing at least 12 contiguous bases in a preprocessed or processed human androgen receptor transcript, and which includes at least 6 contiguous bases of the sequence selected from the group consisting of;
SEQ ID NOS;
2, 7, 8, and 9-22, and(v) capable of hybridizing with a preprocessed human androgen-receptor transcript to form a heteroduplex structure having a Tm of dissociation of at least 45°
C. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21)
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22. A method of confirming the presence of an effective interaction between a human androgen-receptor pre-processed transcript and an uncharged morpholino oligonucleotide analog compound, comprising
(a) administering said compound to the subject, where said compound is characterized by: - (i) 12-40 morpholino subunits, (ii) a substantially uncharged, phosphorus-containing backbone linking said subunits, (iii) active uptake by human prostate cancer cells, (iv) a base sequence that is complementary to a target region containing at least 12 contiguous bases in a preprocessed human androgen receptor transcript, and (v) capable of hybridizing with a preprocessed human androgen-receptor transcript to form a heteroduplex structure having a Tm of dissociation of at least 45°
C.,(b) at a selected time after said administering, obtaining a sample of a body fluid from the subject; and
(c) assaying the sample for the presence of a nuclease-resistant heteroduplex comprising the oligonucleotide analog compound complexed with a complementary-sequence portion of a preprocessed human androgen-receptor transcript.
- (i) 12-40 morpholino subunits, (ii) a substantially uncharged, phosphorus-containing backbone linking said subunits, (iii) active uptake by human prostate cancer cells, (iv) a base sequence that is complementary to a target region containing at least 12 contiguous bases in a preprocessed human androgen receptor transcript, and (v) capable of hybridizing with a preprocessed human androgen-receptor transcript to form a heteroduplex structure having a Tm of dissociation of at least 45°
Specification