US5599796A
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Treatment of urogenital cancer with boron neutron capture therapy
Assignee: Emory University
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Filing: 1994-11-04
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Granted: 1997-02-04
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Expires: 2014-11-04
Abstract
Abstract Methods and compositions for treating urogenital tumors, and particular, cancer of the prostate, bladder, and kidney, with BCNT, are disclosed. Any boron-containing compound that is sufficiently lipophilic to pass through the appropriate urogenital membranes in a quantity high enough to achieve therapy on irradiation with low-energy neutrons can be used. Carboranyl-containing nucleosides and oligonucleotides are particularly suited for use in BNCT of urogenital tumors. Preferred compounds include 5-carboranyl-2'-deoxyuridine (CDU) and 5-o-carboranyl-1-(2-deoxy-2-fluoro- beta -D-arabinofuranosyl)uracil (CFAU). Nucleosides and oligonucleotides bearing an -O-[(carboran-1-yl)alkyl]phosphate, S-[(carboran-1-yl)alkyl]phosphorothioate, or Se-[(carboran-1-yl)alkyl]phosphoroselenoate in place of the (carboran-1-yl)phosphonate moiety can be used. Oligonucleotides of specific gene sequences that include one or more 3',5'-linking-(carboran-1-yl)phosphonate moieties can also be used in antisense therapy in the selective modification of gene expression. Compounds can be used in urogenital BNCT therapy that contain boron clusters as a means to enhance lipophilicity wherein the boron is not enriched in 10B, but instead, in the 11B isotope. The therapy is accomplished by administering the boron-containing compound by any appropriate route, including by intravenous injection, oral delivery or by catheter or other direct means, in such a manner that the compound accumulates in the target tumor. After desired accumulation of the compound in the tumor, the site is irradiated with an effective amount of low energy neutrons.
Inventors
- 👤 Raymond F. Schinazi
- 👤 Thomas E. Keane
- 👤 Dennis C. Liotta
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 12:04
CPC Classifications
C; C07; C07H; C07H21/00; A; A61; A61K; A61K41/00; A61K41/009; A61K41/0095; A61K49/00; A61K49/06; A61K49/08; A61K49/085; A61K49/10; A61P; A61P13/00; A61P13/02; A61P15/00; A61P31/00; A61P31/12; A61P35/00; C07H19/00; C07H19/02; C07H19/04; C07H19/06; C07H19/10; C07H19/16; C07H19/20; C07H23/00; C12; C12N; C12N15/00; C12N15/09; C12N15/10; C12N15/11; C12N15/113; C12N9/00; C12N9/10; C12N9/12; C12N9/1241; C12N9/1276; C12Q; C12Q1/00; C12Q1/68; C12Q1/6813; C12Q1/6816; C12Q1/6827; C12Q1/6876; C12Q1/6883; C12Q1/6886; C12N2310/00; C12N2310/30; C12N2310/31; C12N2310/318; C12N2310/33; C12N2310/35; C12N2310/352; C12N2310/3527
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
37 words
A method for treating a urogenital tumor in a human, comprising administering to the tumor being human an effective amount of a 10 B-containing compound, and irradiating the tumor with sufficient low energy neutrons to achieve cytotoxicity.
Claim 2
Independent Claim
37 words
A method for treating a urogenital tumor in a human, comprising administering to the tumor being human an effective amount of a 10 B-containing compound, and irradiating the tumor with sufficient low energy neutrons to achieve cytotoxicity.
Claim 3
Dependent Claim
13 words
The method of claim 1 wherein the urogenital tumor is in the prostate.
Claim 4
Dependent Claim
13 words
The method of claim 1 wherein the urogenital tumor is in the bladder.
Claim 5
Dependent Claim
13 words
The method of claim 1 wherein the urogenital tumor is in the kidney.
Claim 6
Dependent Claim
20 words
The method of claim 1, wherein the 10 B-containing compound is selected from the group consisting of 5-carboranyl-2'-deoxyuridine and 5-o-carboranyl-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil.
Claim 7
Dependent Claim
154 words
The method of claim 1, wherein the 10 B-containing compound is selected from the group consisting of: ##STR12## wherein R 1 is alkyl, haloalkyl, alkenyl, alkoxyalloyl, aryl, heteroaryl, trifluoromethyl, alkylaryl, arylalkyl, or halogen; R 2 is hydrogen, alkyl, acyl; sulfonate ester; a mono, di or triphosphate ester; trityl or monomethoxytrityl; benzyl optionally substituted with one or more aryl substituents; silyl, or diphenylmethylsilyl; lipid; peptide; or cholesterol; R 3 is hydroxyl, hydrogen, halogen, --CN, --N 3 , lower alkyl, amino, alkylamino, dialkylamino, alkoxy; and wherein the R 3 group can be in the ribosyl or the arabinosyl conformation; B represents the boron moiety of a carboranyl group; W is O, S, or Se; X is O, S, S(O), S(O) 2 , CH 2 , CHOH, CHN 3 or NH; Y is OH, SH, SeH, or halogen; Z=O or S; n is 1-5; m is 0 or 1; and base refers to a purine or pyrimidine.
Claim 8
Dependent Claim
155 words
The method of claim 1, wherein the 10 B-containing compound is selected from the group consisting of ##STR13## wherein R 1 is alkyl, haloalkyl, alkenyl, alkoxyalloyl, aryl, heteroaryl, trifluoromethyl, alkylaryl, arylalkyl, or halogen; R 2 is hydrogen, alkyl, acyl; sulfonate ester; a mono, di or triphosphate ester; trityl or monomethoxytrityl; benzyl optionally substituted with one or more aryl substituents; silyl, or diphenylmethylsilyl; lipid; peptide; or cholesterol; R 3 is hydroxyl, hydrogen, halogen, --CN, --N 3 , lower alkyl, amino, alkylamino, dialkylamino, alkoxy; and wherein the R 3 group can be in the ribosyl or the arabinosyl conformation; B represents the boron moiety of a carboranyl group; W is O, S, or Se; X is O, S, S(O), S(O) 2 , CH 2 , CHOH, CHN 3 or NH; Y is OH, SH, SeH, or halogen; Z=O or S; n is 1-5; m is 0 or 1; and wherein "base" refers to a purine or pyrimidine.
Claim 9
Dependent Claim
38 words
The method of claim 7 wherein the base is selected from the group consisting of thymine, uracil, 5-halouracil, cytosine, 5-halocytosine, 6-azapyrimidine, adenine, guanine, 2,6-diaminopurine, 2-amino-6-chloropurine, 2-aminopurine, 5-lower alkyl uracil, 5-lower alkylcytosine, 2-thiouracil, 2,4-thiouracil, 4-thiouracil, 6-chloropurine, 5-carboranyluracil, and 5-carboranylcytosine.
Claim 10
Dependent Claim
13 words
The method of claim 1 wherein the 10 B-containing compound is an oligonucleotide.
Claim 11
Dependent Claim
20 words
The method of claim 1 wherein the 10 B-containing compound is a nucleoside selected from the group consisting of: ##STR14##
Claim 12
Dependent Claim
31 words
The method of claim 6, wherein B is selected from the group consisting of anionic o-nido-7,8-C 2 B 9 H.sub.(11 or 12) and neutral o-closo-1,2-C 2 B 10 H 12 .
Claim 13
Dependent Claim
31 words
The method of claim 7, wherein B is selected from the group consisting of anionic o-nido-7,8-C 2 B 9 H.sub.(11 or 12) and neutral o-closo-1,2-C 2 B 10 H 12 .
Claim 14
Independent Claim
39 words
A method for treating a urogenital tumor in a host animal, comprising administering to the tumor bearing host animal an effective amount of a 10 B-containing compound, and irradiating the tumor with sufficient low energy neutrons to achieve cytotoxicity.
Claim 15
Independent Claim
39 words
A method for treating a urogenital tumor in a host animal, comprising administering to the tumor bearing host animal an effective amount of a 10 B-containing compound, and irradiating the tumor with sufficient low energy neutrons to achieve cytotoxicity.
Claim 16
Dependent Claim
10 words
The method of claim 6 wherein R 2 is acetyl.
Claim 17
Dependent Claim
10 words
The method of claim 6 wherein R 2 is trialkylsilyl.
Claim 18
Dependent Claim
16 words
The method of claim 6 wherein B is anionic o-nido-7,8-C 2 B 9 H.sub.(11 or 12).
Claim 19
Dependent Claim
16 words
The method of claim 6 wherein B is neutral o-closo-1,2-C 2 B 10 H 12 .
Claim 20
Dependent Claim
10 words
The method of claim 7 wherein R 2 is acetyl.
Claim 21
Dependent Claim
10 words
The method of claim 7 wherein R 2 is trialkylsilyl.
Claim 22
Dependent Claim
16 words
The method of claim 7 wherein B is anionic o-nido-7,8-C 2 B 9 H.sub.(11 or 12).
Claim 23
Dependent Claim
16 words
The method of claim 7 wherein B is neutral o-closo-1,2-C 2 B 10 H 12 .
References Cited (Backward Citations)
US4855493A
Cited
US4516535A
Cited
US5328678A
Cited
US5021572A
Cited
US5066479A
Cited
US4959356A
Cited
US5130302A
Cited
WO1993017028A1
Cited
US5405598A
Cited
US5272250A
Cited
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| 3.5 Years (Year 4) | 2000-02-04 | 2000-08-05 | 2001-02-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-02-04 | 2004-08-05 | 2005-02-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-02-04 | 2008-08-05 | 2009-02-04 | $7700.00 | Window Closed / Lapsed |