US4880918A
Expired / Lapsed
US
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Arrest and killing of tumor cells by adenosine 5-diphosphate and adenosine-5-triphosphate
Assignee: Individual
•
Filing: 1982-07-13
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Granted: 1989-11-14
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Expires: 2002-07-13
Abstract
Abstract A process by which the growth of malignant cells, e.g., human malignant cells, in a host is arrested and killed by treatment of the cells with low doses of adenosine 5'-diphosphate (ADP) or adenosine 5'-triphosphate (ATP), while normal cells thereof are substantially unaffected, is disclosed. ADP and ATP are capable of permeating through the plasma membrane of a variety of tumor cells, e.g., human tumor cells, and are incorporated into the cellular acid-soluble nucleotide pools of these cells, without prior breakdown to adenosine 5'-monophosphate (AMP) or adenosine, resulting in inhibition of DNA synthesis and cellular growth followed by cell death, while normal animal cells do not allow penetration of ADP or ATP through their plasma membrane without prior degradation.
Inventors
- 👤 Eliezer Rapaport
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 21:21
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61P; A61P35/00; C; C07; C07H; C07H19/00; C07H19/02; C07H19/04; C07H19/16; C07H19/20
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
70 words
A process for selectively entering and arresting the growth of tumor cells in a host while substantially not affecting normal cells thereof comprising the step of exposing said tumor cells to low doses of at least one of adenosine 5'-diphosphate and adenosine 5'-triphosphate, in a pharmaceutical preparation, said low doses being in an amount sufficient to inhibit DNA synthesis in said tumor cells while said normal cells are substantially unaffected.
Claim 2
Dependent Claim
70 words
A process for selectively entering and arresting the growth of tumor cells in a host while substantially not affecting normal cells thereof comprising the step of exposing said tumor cells to low doses of at least one of adenosine 5'-diphosphate and adenosine 5'-triphosphate, in a pharmaceutical preparation, said low doses being in an amount sufficient to inhibit DNA synthesis in said tumor cells while said normal cells are substantially unaffected.
Claim 3
Dependent Claim
17 words
A process according to claim 1, wherein said low doses are within the range of 25-100 μM.
Claim 4
Dependent Claim
17 words
A process according to claim 2, wherein said low doses are within the range of 40-80 μM.
Claim 5
Dependent Claim
28 words
A process according to claim 1 or 2, wherein said step of exposing continues for more than 48 hours, whereby significant numbers of said tumor cells are killed.
Claim 6
Dependent Claim
14 words
A process according to claim 4, wherein said tumor cells are human tumor cells.
Claim 7
Dependent Claim
15 words
A process according to claim 5, wherein said human tumor cells are a solid tumor.
Claim 8
Dependent Claim
24 words
A process according to claim 5, wherein said human tumor cells are selected from the group consisting of CAPAN-1, BxPc, HT29, HS294T and HS584T.
Claim 9
Dependent Claim
30 words
A process according to claim 1, wherein said step of exposing includes delivering said adenosine 5'-diphosphate, adenosine 5'-triphosphate or pharmaceutically acceptable salt thereof to the site of said tumor cells.
Claim 10
Dependent Claim
21 words
A process according to claim 8, wherein said delivering is accomplished by injection, infusion, oral administrating, enteral application or topical application.
Claim 11
Dependent Claim
29 words
A process according to claim 9, wherein said delivering is accomplished by oral administration or topical application, with a dosage of 1-100 mg/kg of body weight of said host.
Claim 12
Dependent Claim
25 words
A process according to claim 9, wherein said delivering is accomplished by injection, with a dosage of 0.05-20 mg/kg of body weight of said host.
Claim 13
Dependent Claim
27 words
A process according to claim 9, wherein said delivering is accomplished by infusion, at a rate of 0.01-1.5 mg/kg of body weight of said host per minute.
Claim 14
Dependent Claim
30 words
A process according to claim 1, wherein said at least one of adenosine 5'-diphosphate and adenosine 5'-triphosphate, in a pharmaceutical preparation, is a salt of adenosine 5'-diphosphate or adenosine 5'-triphosphate.
Claim 15
Dependent Claim
13 words
A process according to claim 13, wherein said salt is a complex salt.
Claim 16
Dependent Claim
75 words
A process for selectively entering and arresting the growth of tumor cells in the presence of normal cells, while substantially not affecting said normal cells, comprising the step of exposing said tumor cells in the presence of normal cells to low doses of adenosine 5'-diphosphate or adenosine 5'-triphosphate, in a pharmaceutical preparation, said low doses being in an amount sufficient to inhibit DNA synthesis in said tumor cells while said normal cells are substantially unaffected.
Claim 17
Dependent Claim
75 words
A process for selectively entering and arresting the growth of tumor cells in the presence of normal cells, while substantially not affecting said normal cells, comprising the step of exposing said tumor cells in the presence of normal cells to low doses of adenosine 5'-diphosphate or adenosine 5'-triphosphate, in a pharmaceutical preparation, said low doses being in an amount sufficient to inhibit DNA synthesis in said tumor cells while said normal cells are substantially unaffected.
Claim 18
Dependent Claim
26 words
A process according to claim 15, wherein said step of exposing continues for more than 48 hours, whereby significant numbers of said tumor cells are killed.
Claim 19
Dependent Claim
17 words
A process according to claim 16, wherein said low doses are within the range of 25-100 μM.
Claim 20
Dependent Claim
14 words
A process according to claim 17, wherein said tumor cells are human tumor cells.
Claim 21
Dependent Claim
27 words
A process according to claim 18, wherein said adenosine 5'-diphosphate or adenosine 5'-triphosphate, in a pharmaceutical preparation, comprises adenosine 5'-diphosphate, adenosine 5'-triphosphate or pharmaceutically acceptable salts thereof.
Claim 22
Dependent Claim
15 words
A process according to claim 19, wherein said human tumor cells are a solid tumor.
Claim 23
Dependent Claim
24 words
A process according to claim 20, wherein said human tumor cells are selected from the group consisting of CAPAN-1, BxPc, HT29, HS294T and HS584T.
Claim 24
Dependent Claim
87 words
A process according to claim 1 or 15, wherein said tumor cells have a plasma membrane such that the adenosine 5'-diphosphate and adenosine 5'-triphosphate can selectively permeate therethrough while not permeating through the plasma membrane of normal cells, whereby the adenosine 5'-diphosphate and adenosine 5'-triphosphate, without prior degradation to adenosine 5'-monophosphate or adenosine, can selectively permeate through the plasma membranes of the tumor cells and not through the normal cells, whereby DNA synthesis in the tumor cells is inhibited while said normal cells are substantially not affected.
Claim 25
Dependent Claim
29 words
A process according to claim 22, wherein said doses are sufficient to arrest the growth of significant portions of said tumor cells in the S phase of their cycle.
Claim 26
Dependent Claim
14 words
A process according to claim 22, wherein said tumor cells are malignant tumor cells.
Claim 27
Dependent Claim
50 words
A process according to claim 1, wherein said at least one of adenosine 5'-diphosphate and adenosine 5'-triphosphate, in a pharmaceutical preparation, includes organic or inorganic materials suitable for internal administration into the host, in addition to at least one of adenosine 5'-diphosphate, adenosine 5'-triphosphate, and pharmaceutically acceptable salt forms thereof.
Claim 28
Dependent Claim
31 words
A process according to claim 1 or 15, wherein said doses are sufficient to arrest the growth of significant portions of said tumor cells in the S phase of their cycle.
Claim 29
Dependent Claim
38 words
A process according to claim 1, 2, 15 or 17, wherein said tumor cells have lesions in the plasma membrane permitting permeation of adenosine 5'-diphosphate or adenosine 5'-triphosphate therethrough without prior degradation thereof to adenosine 5'-monophosphate or adenosine.
Claim 30
Dependent Claim
83 words
A process for selectively permeating adenosine 5'-diphosphate or adenosine 5'-triphosphate into tumor cells in the presence of normal cells, without prior degradation of the adenosine 5'-diphosphate or adenosine 5'-triphosphate and without permeation of adenosine 5'-diphosphate or adenosine 5'-triphosphate into said normal cells, comprising the step of exposing said tumor cells in the presence of normal cells to low doses of at least one of adenosine 5'-diphosphate and adenosine 5'-triphosphate, in a pharmaceutical preparation, said low doses being within the range of 25-100 μM.
Claim 31
Dependent Claim
83 words
A process for selectively permeating adenosine 5'-diphosphate or adenosine 5'-triphosphate into tumor cells in the presence of normal cells, without prior degradation of the adenosine 5'-diphosphate or adenosine 5'-triphosphate and without permeation of adenosine 5'-diphosphate or adenosine 5'-triphosphate into said normal cells, comprising the step of exposing said tumor cells in the presence of normal cells to low doses of at least one of adenosine 5'-diphosphate and adenosine 5'-triphosphate, in a pharmaceutical preparation, said low doses being within the range of 25-100 μM.
Claim 32
Dependent Claim
23 words
A process according to claim 28, wherein said tumor cells are selected from the group consisting of CAPAN-1, BxPc, HT29, HS294T and Hs584T.
Claim 33
Dependent Claim
14 words
A process according to claim 29, wherein said tumor cells are in a host.
Claim 34
Dependent Claim
34 words
A process according to claim 28, wherein said tumor cells have lesions in the plasma membrane permitting permeation of adenosine 5'-diphosphate or adenosine 5'-triphosphate therethrough without prior degradation thereof to adenosine 5'-monophosphate or adenosine.
Claim 35
Dependent Claim
17 words
A process according to claim 1, 15 or 28, wherein said tumor cells are malignant tumor cells.
References Cited (Backward Citations)
US4396609A
Cited
JPS5634697A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1992-11-13 | 1993-05-15 | 1993-11-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-11-13 | 1997-05-15 | 1997-11-14 | $3760.00 | Window Closed / Lapsed |
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