US2009209747A1PendingUtilityA1
Method to inhibit cell growth using oligonucleotides
Est. expiryJun 6, 2015(expired)· nominal 20-yr term from priority
A61P 43/00A61P 35/00A61P 7/00A61P 35/02A61P 1/18A61P 15/00A61K 31/7088A61P 17/00A61K 31/713A61K 31/7125A61P 21/00A61P 19/00A61K 31/711A61K 48/00
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Claims
Abstract
Described are methods for treating hyperproliferative disorders, including cancers, by administering to the affected mammal (e.g., human) an effective amount of a composition comprising one or more oligonucleotides which share at least 33% but less than 100% nucleotide sequence identity with the human telomere overhang repeat. Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, atopic dermatitis, or hyperprolferative diseases of other epithelia and methods for reducing photoaging, or oxidative stress or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are also disclosed. The compositions and methods are also useful to treating other cancers.
Claims
exact text as granted — not AI-modified1 . A composition comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less.
2 . The composition of claim 1 wherein said oligonucleotide lacks cytosine.
3 . The composition of claim 1 wherein said oligonucleotide comprises one or more sequences selected from the group consisting of TT, TA, TG, AG, GG, AT, GT, TTA, TAG, TAT, ATG, AGT, AGG, GAG, GGG, TTAG, TAGG, AGGG, GGTT, GTTA, TTAGG, TAGGG,GGTTA, GTTAG, GGGTT and GGGGTT.
4 . The composition of claim 1 wherein said oligonucleotide is between 40% and 90% identical to (TTAGGG) n .
5 . The composition of claim 1 wherein said oligonucleotide is selected from the group consisting of oligonucleotides 2-200 nucleotides long; oligonucleotides 2-20 nucleotides long; oligonucleotides 5-16 nucleotides long; and oligonucleotides 2-5 nucleotides long.
6 . The composition according to claim 1 wherein said one or more oligonucleotide is selected from the group consisting of:
G GTTAGGGTGTAGGTTT;
(SEQ ID NO: 28)
GGTTGGTTGGTTGGTT;
(SEQ ID NO: 29)
GGTGGTGGTGGTGGT;
(SEQ ID NO: 30)
GGAGGAGGAGGAGGA;
(SEQ ID NO: 31)
GGTGTGGTGTGGTGT;
(SEQ ID NO: 32)
TAGTGTTAGGTGTAG;
(SEQ ID NO: 34)
GAGTATGAG;
(SEQ ID NO: 37)
AGTATGA; GTTAGGGTTAG;
(SEQ ID NO: 2)
GGTAGGTGTAGGATT;
(SEQ ID NO: 10)
GGTAGGTGTAGGTTA;
(SEQ ID NO: 11)
GGTTAGGTGTAGGTT;
(SEQ ID NO: 12)
GGTTAGGTGGAGGTTT;
(SEQ ID NO: 13)
GGTTAGGTTAGGTTA;
(SEQ ID NO: 15)
GTTAGGTTTAAGGTT;
(SEQ ID NO: 19)
and
GTTAGGGTTAGGGTT.
(SEQ ID NO: 22)
7 . A method of treating a hyperproliferative disorder in a mammal the method comprising administering to the mammal an effective amount of a composition comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less.
8 . The method of claim 7 wherein said oligonucleotide lacks cytosine.
9 . The method of claim 7 wherein said oligonucleotide comprising one or more sequences selected from the group consisting of TT, TA, TG, AG, GG, AT, GT, TTA, TAG, TAT, ATG, AGT, AGG, GAG, GGG, TTAG, TAGG, AGGG, GGTT, GTTA, TTAGG, TAGGG,GGTTA, GTTAG, GGGTT and GGGGTT.
10 . The method of claim 7 wherein said oligonucleotide is between 40% and 90% identical to (TTAGGG) n .
11 . The method of claim 7 wherein said oligonucleotide is selected from the group consisting of a) oligonucleotides 2-200 nucleotides long; b) oligonucleotides 2-20 nucleotides long; c) oligonucleotides 5-16 nucleotides long; and d) oligonucleotides 2-5 nucleotides long.
12 . The method according to claim 7 wherein the said one or more oligonucleotide is selected from the group consisting of:
G GTTAGGGTGTAGGTTT;
(SEQ ID NO: 28)
GGTTGGTTGGTTGGTT;
(SEQ ID NO: 29)
GGTGGTGGTGGTGGT;
(SEQ ID NO: 30)
GGAGGAGGAGGAGGA;
(SEQ ID NO: 31)
GGTGTGGTGTGGTGT;
(SEQ ID NO: 32)
TAGTGTTAGGTGTAG;
(SEQ ID NO: 34)
GAGTATGAG;
(SEQ ID NO: 37)
AGTATGA; GTTAGGGTTAG;
(SEQ ID NO: 2)
GGTAGGTGTAGGATT;
(SEQ ID NO: 10)
GGTAGGTGTAGGTTA;
(SEQ ID NO: 11)
GGTTAGGTGTAGGTT;
(SEQ ID NO: 12)
GGTTAGGTGGAGGTTT;
(SEQ ID NO: 13)
GGTTAGGTTAGGTTA;
(SEQ ID NO: 15)
GTTAGGTTTAAGGTT;
(SEQ ID NO: 19)
and
GTTAGGGTTAGGGTT.
(SEQ ID NO: 22)
13 . A method for inhibiting growth of cancer cells in a human comprising administering to the human an effective amount of a composition comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less.
14 . The method of claim 13 wherein said oligonucleotide lacks cytosine.
15 . The method of claim 13 wherein said oligonucleotide comprising one or more sequences selected from the group consisting of TT, TA, TG, AG, GG, AT, GT, TTA, TAG, TAT, ATG, AGT, AGG, GAG, GGG, TTAG, TAGG, AGGG, GGTT, GTTA, TTAGG, TAGGG,GGTTA, and GTTAG.
16 . The method of claim 13 wherein said oligonucleotides is selected from the group consisting of a) oligonucleotides 2-200 nucleotides long; b) oligonucleotides 2-20 nucleotides long; c) oligonucleotides 5-16 nucleotides long; and d) oligonucleotides 2-5 nucleotides long.
17 . The method of claim 13 wherein said oligonucleotide is between 40% and 90% identical to (TTAGGG) n .
18 . The method of claim 13 wherein said one or more oligonucleotide is selected from the group consisting of: GGTTAGGGTGTAGGTTT (SEQ ID NO: 28); GGTTGGTTGGTTGGTT (SEQ ID NO: 29); GGTGGTGGTGGTGGT (SEQ ID NO: 30); GGAGGAGGAGGAGGA (SEQ ID NO: 31); GGTGTGGTGTGGTGT (SEQ ID NO: 32); TAGTGTTAGGTGTAG (SEQ ID NO: 34); GAGTATGAG (SEQ ID NO: 37); AGTATGA; GTTAGGGTTAG (SEQ ID NO: 2); GGTAGGTGTAGGATT (SEQ ID NO: 10); GGTAGGTGTAGGTTA (SEQ ID NO: 11); GGTTAGGTGTAGGTT (SEQ ID NO: 12); GGTTAGGTGGAGGTTT (SEQ ID NO: 13); GGTTAGGTTAGGTTA (SEQ ID NO: 15); GTTAGGTTTAAGGTT (SEQ ID NO: 19); and GTTAGGGTTAGGGTT (SEQ ID NO: 22).
19 . The method of claim 13 wherein the cancer cells are selected from the group consisting of melanoma cells, breast cancer cells, lymphoma cells, osteosarcoma cells, leukemia cells, squamous carcinoma cells, cervical cancer cells, ovarian cancer cells, pancreatic cancer cells, and fibrosarcoma cells.
20 . A method of promoting differentiation of malignant cells in a mammal comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less.
21 . The method of claim 20 wherein said oligonucleotide lacks cytosine.
22 . The method of claim 20 wherein said oligonucleotide comprising one or more sequences selected from the group consisting of TT, TA, TG, AG, GG, AT, GT, TTA, TAG, TAT, ATG, AGT, AGG, GAG, GGG, TTAG, TAGG, AGGG, GGTT, GTTA, TTAGG, TAGGG,GGTTA, GTTAG, GGGTT and GGGGTT.
23 . The method of claim 20 wherein said oligonucleotides is selected from the group consisting of a) oligonucleotides 2-200 nucleotides long; b) oligonucleotides 2-20 nucleotides long; c) oligonucleotides 5-16 nucleotides long; and d) oligonucleotides 2-5 nucleotides long.
24 . The method of claim 20 wherein said oligonucleotide is between 40% and 90% identical to (TTAGGG) n .
25 . The method of claim 20 wherein said one or more oligonucleotide is selected from the group consisting of: GGTTAGGGTGTAGGTTT (SEQ ID NO: 28); GGTTGGTTGGTTGGTT (SEQ ID NO: 29); GGTGGTGGTGGTGGT (SEQ ID NO: 30); GGAGGAGGAGGAGGA (SEQ ID NO: 31); GGTGTGGTGTGGTGT (SEQ ID NO: 32); TAGTGTTAGGTGTAG (SEQ ID NO: 34); GAGTATGAG (SEQ ID NO: 37); AGTATGA; GTTAGGGTTAG (SEQ ID NO: 2); GGTAGGTGTAGGATT (SEQ ID NO: 10); GGTAGGTGTAGGTTA (SEQ ID NO: 11); GGTTAGGTGTAGGTT (SEQ ID NO: 12); GGTTAGGTGGAGGTTT (SEQ ID NO: 13); GGTTAGGTTAGGTTA (SEQ ID NO: 15); GTTAGGTTTAAGGTT (SEQ ID NO: 19); and GTTAGGGTTAGGGTT (SEQ ID NO: 22).
26 . The method of claim 20 wherein the cancer cells are selected from the group consisting of melanoma cells, breast cancer cells, lymphoma cells, osteosarcoma cells, leukemia cells, squamous carcinoma cells, cervical cancer cells, ovarian cancer cells, pancreatic cancer cells, and fibrosarcoma cells.
27 . A method of inducing apoptosis in a cancer cell said method comprising administering to the mammal one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less.
28 . The method of claim 27 wherein said oligonucleotide lacks cytosine.
29 . The method of claim 27 wherein said oligonucleotide comprising one or more sequences selected from the group consisting of TT, TA, TG, AG, GG, AT, GT, TTA, TAG, TAT, ATG, AGT, AGG, GAG, GGG, TTAG, TAGG, AGGG, GGTT, GTTA, TTAGG, TAGGG,GGTTA, GTTAG, GGGTT and GGGGTT.
30 . The method of claim 27 wherein said oligonucleotides is selected from the group consisting of a) oligonucleotides 2-200 nucleotides long; b) oligonucleotides 2-20 nucleotides long; c) oligonucleotides 5-16 nucleotides long; and d) oligonucleotides 2-5 nucleotides long.
31 . The method of claim 27 wherein said oligonucleotide is between 40% and 90% identical to (TTAGGG) n .
32 . The method according to claim 27 wherein said one or more oligonucleotide is selected from the group consisting of:
G GTTAGGGTGTAGGTTT;
(SEQ ID NO: 28)
GGTTGGTTGGTTGGTT;
(SEQ ID NO: 29)
GGTGGTGGTGGTGGT;
(SEQ ID NO: 30)
GGAGGAGGAGGAGGA;
(SEQ ID NO: 31)
GGTGTGGTGTGGTGT;
(SEQ ID NO: 32)
TAGTGTTAGGTGTAG;
(SEQ ID NO: 34)
GAGTATGAG;
(SEQ ID NO: 37)
AGTATGA; GTTAGGGTTAG;
(SEQ ID NO: 2)
GGTAGGTGTAGGATT;
(SEQ ID NO: 10)
GGTAGGTGTAGGTTA;
(SEQ ID NO: 11)
GGTTAGGTGTAGGTT;
(SEQ ID NO: 12)
GGTTAGGTGGAGGTTT;
(SEQ ID NO: 13)
GGTTAGGTTAGGTTA;
(SEQ ID NO: 15)
GTTAGGTTTAAGGTT
(SEQ ID NO: 19)
and
GTTAGGGTTAGGGTT.
(SEQ ID NO: 22)
33 . The method of claim 27 wherein the cancer cells are selected from the group consisting of melanoma cells, breast cancer cells, lymphoma cells, osteosarcoma cells, leukemia cells, squamous carcinoma cells, cervical cancer cells, ovarian cancer cells, pancreatic cancer cells, and fibrosarcoma cells.
34 . The method for reducing the occurrence of skin cancer in a human the method comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less.
35 . The method of claim 34 wherein said oligonucleotide lacks cytosine.
36 . The method of claim 34 wherein said oligonucleotide comprising one or more sequences selected from the group consisting of TT, TA, TG, AG, GG, AT, GT, TTA, TAG, TAT, ATG, AGT, AGG, GAG, GGG, TTAG, TAGG, AGGG, GGTT, GTTA, TTAGG, TAGGG,GGTTA, GTTAG, GGGTT and GGGGTT.
37 . The method of claim 34 wherein said oligonucleotides is selected from the group consisting of a) oligonucleotides 2-200 nucleotides long; b) oligonucleotides 2-20 nucleotides long; c) oligonucleotides 5-16 nucleotides long; and d) oligonucleotides 2-5 nucleotides long.
38 . The method of claim 34 wherein said oligonucleotide is between 40% and 90% identical to (TTAGGG) n .
39 . The method of claim 34 wherein said one or more oligonucleotide is selected from the group consisting of: GGTTAGGGTGTAGGTTT (SEQ ID NO: 28); GGTTGGTTGGTTGGTT (SEQ ID NO: 29); GGTGGTGGTGGTGGT (SEQ ID NO: 30); GGAGGAGGAGGAGGA (SEQ ID NO: 31); GGTGTGGTGTGGTGT (SEQ ID NO: 32); TAGTGTTAGGTGTAG (SEQ ID NO: 34); GAGTATGAG (SEQ ID NO: 37); AGTATGA; GTTAGGGTTAG (SEQ ID NO: 2); GGTAGGTGTAGGATT (SEQ ID NO: 10); GGTAGGTGTAGGTTA (SEQ ID NO: 11); GGTTAGGTGTAGGTT (SEQ ID NO: 12); GGTTAGGTGGAGGTTT (SEQ ID NO: 13); GGTTAGGTTAGGTTA (SEQ ID NO: 15); GTTAGGTTTAAGGTT (SEQ ID NO: 19); and GTTAGGGTTAGGGTT (SEQ ID NO: 22).
40 . The method of claim 34 wherein the cancer cells are selected from the group consisting of melanoma cells, breast cancer cells, lymphoma cells, osteosarcoma cells, leukemia cells, squamous carcinoma cells, cervical cancer cells, ovarian cancer cells, pancreatic cancer cells, and fibrosarcoma cells.Join the waitlist — get patent alerts
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