US4925664A
Expired / Lapsed
US
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Spider toxins and methods for their use as blockers of calcium channels and amino acid receptor function
Assignee: University of Utah Research Foundation Inc
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Filing: 1986-10-20
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Granted: 1990-05-15
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Expires: 2006-10-20
Abstract
Abstract Methods and compositions for blocking various channels and receptors within an organism are provided. For example, two toxins were isolated from the Agelenopsis aperta spider. The first toxin comprised a toxin having a molecular weight of from approximately 5,000 to approximately 10,000. This toxin was found to have an irreversible effect on calcium channels within the central nervous system. A second toxin having a molecular weight of less than about 1,000 was also isolated. This toxin was found to have a reversible blocking effect on calcium channels within the central nervous system and the cardiovascular system. A third toxin was isolated from the Argiope aurantia spider. This toxin was found to have a reversible effect on excitatory amino acid receptors. Finally, a toxin having a molecular weight of from approximately 5,000 to approximately 7,000 daltons was isolated from the Hololena Curta spider. This toxin was found to have an irreversible effect on excitatory amino acid receptors. The present invention further relates to methods of treating heart and neurological diseases by applying the toxins isolated and identified. In particular, the low molecular weight toxin from Agelenopsis aperta may provide a treatment of certain heart conditions such as arrhythmia, angina, Hypertension, and congestive heart failure. In addition, the toxins may provide beneficial effects on certain neurological conditions including seizures. It is also found that the toxins having an irreversible effect are effective as tags in probing the various components within the calcium channels and excitatory amino acid receptors and are effective insecticides and anthelmintics.
Inventors
- 👤 J. R. Hunter Jackson
- 👤 Thomas N. Parks
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 06:24
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/43504; C07K14/43513; C07K14/43518; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S530/00; Y10S530/855
Claims Analysis
Total Claims: 65
Claim 1
Independent Claim
31 words
A composition functioning as a calcium channel blocker comprising at least one toxin isolated from spider venom, said at least one toxin being capable of functioning as a calcium channel blocker.
Claim 2
Dependent Claim
31 words
A composition functioning as a calcium channel blocker comprising at least one toxin isolated from spider venom, said at least one toxin being capable of functioning as a calcium channel blocker.
Claim 3
Dependent Claim
24 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein the effects of said at least one toxin are reversible.
Claim 4
Dependent Claim
24 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein the effects of said at least one toxin are irreversible.
Claim 5
Dependent Claim
27 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein said at least one toxin blocks calcium channels in the human cardiovascular system.
Claim 6
Dependent Claim
27 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein said at least one toxin blocks calcium channels in the human nervous system.
Claim 7
Dependent Claim
26 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein said at least one toxin is obtained from the Agelenopsis aperta spider.
Claim 8
Dependent Claim
38 words
A composition functioning as a calcium channel blocker as defined in claim 6 wherein said at least one toxin comprises a low molecular weight toxin having a molecular weight of between approximately 200 daltons and approximately 1,000 daltons.
Claim 9
Dependent Claim
37 words
A composition functioning as a calcium channel blocker as defined in claim 6 wherein said at least one toxin comprises a high molecular weight toxin having a molecular weight of from about 5,000 to about 10,000 daltons.
Claim 10
Dependent Claim
29 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein the at least one toxin selectively blocks calcium channels and does not block other channels.
Claim 11
Dependent Claim
23 words
A composition functioning as a calcium channel blocker as defined in claim 1 wherein said at least one toxin is not acutely cytotoxic.
Claim 12
Dependent Claim
52 words
A composition functioning as a calcium channel blocker comprising at least one toxin extracted from whole spider venom, which extracted spider toxin functions as a calcium channel blocker and blocks calcium channels in both the cardiovascular and nervous systems without significant undesirable side effects that would mask the calcium channel blocker effect.
Claim 13
Dependent Claim
52 words
A composition functioning as a calcium channel blocker comprising at least one toxin extracted from whole spider venom, which extracted spider toxin functions as a calcium channel blocker and blocks calcium channels in both the cardiovascular and nervous systems without significant undesirable side effects that would mask the calcium channel blocker effect.
Claim 14
Dependent Claim
21 words
A composition functioning as a calcium channel blocker as defined in claim 11 wherein the effects of said toxin are reversible.
Claim 15
Dependent Claim
25 words
A composition functioning as a calcium channel blocker as defined in claim 11 wherein the toxin is extracted from venom of the Agelenopsis aperta spider.
Claim 16
Dependent Claim
28 words
A composition functioning as a calcium channel blocker as defined in claim 13 wherein the toxin has a molecular weight of from approximately 200 to approximately 1,000 daltons.
Claim 17
Dependent Claim
42 words
A composition functioning as a calcium channel blocker comprising at least one toxin extracted from whole spider venom, which extracted spider toxin functions as a calcium channel blocker, and which blocks calcium channels in the nervous system, but not the cardiovascular system.
Claim 18
Dependent Claim
42 words
A composition functioning as a calcium channel blocker comprising at least one toxin extracted from whole spider venom, which extracted spider toxin functions as a calcium channel blocker, and which blocks calcium channels in the nervous system, but not the cardiovascular system.
Claim 19
Dependent Claim
25 words
A composition functioning as a calcium channel blocker as defined in claim 15 wherein the toxin is extracted from venom of the Agelenopsis aperta spider.
Claim 20
Dependent Claim
28 words
A composition functioning as a calcium channel blocker as defined in claim 16 wherein the toxin has a molecular weight of from about 5,000 to about 10,000 daltons.
Claim 21
Dependent Claim
21 words
A composition functioning as a calcium channel blocker as defined in claim 17 wherein the effects of said toxin are irreversible.
Claim 22
Dependent Claim
32 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease in humans comprising a calcium channel blocker comprising at least one toxin extracted from spider venom.
Claim 23
Dependent Claim
32 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease in humans comprising a calcium channel blocker comprising at least one toxin extracted from spider venom.
Claim 24
Dependent Claim
31 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease as defined in claim 19 wherein the toxin is extracted form the Agelenopsis aperta spider.
Claim 25
Dependent Claim
36 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease as defined in claim 20 wherein the toxin has a molecular weight of between approximately 200 and approximately 1,000 daltons.
Claim 26
Dependent Claim
28 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease as defined in claim 21 wherein the cardiovascular disease treated is angina.
Claim 27
Dependent Claim
28 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease as defined in claim 21 wherein the cardiovascular disease treated is hypertension.
Claim 28
Dependent Claim
28 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease as defined in claim 21 wherein the cardiovascular disease treated is arrhythmia.
Claim 29
Dependent Claim
30 words
A composition functioning as a calcium channel blocker suitable for use in treatment of cardiovascular disease as defined in claim 21 wherein the cardiovascular disease treated is congestive heart failure.
Claim 30
Dependent Claim
43 words
A composition functioning as a calcium channel blocker suitable for use in treatment of neurological disorders in humans comprising a toxin extracted from the venom of the Agelenopsis aperta spider and having a molecular weight of from approximately 200 to approximately 1,000 daltons.
Claim 31
Dependent Claim
43 words
A composition functioning as a calcium channel blocker suitable for use in treatment of neurological disorders in humans comprising a toxin extracted from the venom of the Agelenopsis aperta spider and having a molecular weight of from approximately 200 to approximately 1,000 daltons.
Claim 32
Dependent Claim
27 words
A composition functioning as a calcium channel blocker suitable for use in treatment of neurological disorders as defined in claim 24 wherein the disorder treated is epilepsy.
Claim 33
Dependent Claim
28 words
A composition functioning as a calcium channel blocker suitable for use in treatment of neurological disorders as defined in claim 24 wherein the disorder treated is Alzheimer's disease.
Claim 34
Dependent Claim
33 words
A composition functioning as a calcium channel blocker comprising a toxin extracted from the venom of the Agelenopsis aperta spider and having a molecular weight of from about 5,000 to about 10,000 daltons.
Claim 35
Dependent Claim
33 words
A composition functioning as a calcium channel blocker comprising a toxin extracted from the venom of the Agelenopsis aperta spider and having a molecular weight of from about 5,000 to about 10,000 daltons.
Claim 36
Dependent Claim
31 words
A composition functioning as a calcium channel blocker as defined in claim 27 which irreversibly blocks synaptic transmission in chick cochlear nucleus at an EC 50 of less than 1 micromolar.
Claim 37
Dependent Claim
20 words
A composition functioning as a calcium channel blocker as defined in claim 30 wherein the composition is not acutely cytotoxic.
Claim 38
Dependent Claim
33 words
A composition functioning as a calcium channel blocker comprising a toxin extracted from the venom of the Agelenopsis aperta spider and having a molecular weight of from approximately 500 to approximately 1,500 daltons.
Claim 39
Dependent Claim
33 words
A composition functioning as a calcium channel blocker comprising a toxin extracted from the venom of the Agelenopsis aperta spider and having a molecular weight of from approximately 500 to approximately 1,500 daltons.
Claim 40
Dependent Claim
24 words
A composition functioning as a calcium channel blocker as defined in claim 32 wherein the toxin reversibly blocks synaptic transmission in chick cochlear nucleus.
Claim 41
Dependent Claim
24 words
A composition functioning as a calcium channel blocker as defined in claim 33 which blocks the calcium influx in patchclamp experiments on cardiac muscle.
Claim 42
Dependent Claim
33 words
A composition functioning as a calcium channel blocker comprising a toxin extracted from the venom of the Hololena curta spider and having a molecular weight of from about 5,000 to about 7,000 daltons.
Claim 43
Dependent Claim
33 words
A composition functioning as a calcium channel blocker comprising a toxin extracted from the venom of the Hololena curta spider and having a molecular weight of from about 5,000 to about 7,000 daltons.
Claim 44
Dependent Claim
34 words
A composition functioning as a calcium channel blocker as defined in claim 35 wherein the toxin irreversibly blocks post synaptic responses in chick cochlear nucleus at an EC 50 of less than 5 micromolar.
Claim 45
Dependent Claim
25 words
An anthelmintic composition functioning as a calcium channel blocker consisting essentially of at least one toxin extracted from the venom of the Agelenopsis aperta spider.
Claim 46
Dependent Claim
25 words
An anthelmintic composition functioning as a calcium channel blocker consisting essentially of at least one toxin extracted from the venom of the Agelenopsis aperta spider.
Claim 47
Dependent Claim
22 words
An anthelmintic as defined in claim 37 wherein the toxin has a molecular weight of from about 500 to about 1,500 daltons.
Claim 48
Dependent Claim
22 words
An anthelmintic as defined in claim 37 wherein the toxin has a molecular weight of from about 7,000 to about 10,000 daltons.
Claim 49
Dependent Claim
24 words
An anthelmintic comprising a toxin extracted from the Hololena curta spider and having a molecular weight of from about 5,000 to about 7,000 daltons.
Claim 50
Dependent Claim
24 words
An anthelmintic comprising a toxin extracted from the Hololena curta spider and having a molecular weight of from about 5,000 to about 7,000 daltons.
Claim 51
Dependent Claim
36 words
A composition functioning as a calcium channel blocker comprising at least one toxin extracted from Hololena curta spider venom and having a molecular weight in the range of from about 5,000 daltons to about 7,000 daltons.
Claim 52
Dependent Claim
36 words
A composition functioning as a calcium channel blocker comprising at least one toxin extracted from Hololena curta spider venom and having a molecular weight in the range of from about 5,000 daltons to about 7,000 daltons.
Claim 53
Dependent Claim
21 words
A composition functioning as a calcium channel blocker as defined in claim 41 wherein the effects of said toxin are irreversible.
Claim 54
Dependent Claim
48 words
A pharmaceutical composition comprising a carrier and at least one toxin isolated from spider venom, said at least one toxin being capable of functioning as a calcium channel blocker, wherein said pharmaceutical composition blocks calcium channels without undesirable side effects that would mask the calcium channel blocker effect.
Claim 55
Dependent Claim
48 words
A pharmaceutical composition comprising a carrier and at least one toxin isolated from spider venom, said at least one toxin being capable of functioning as a calcium channel blocker, wherein said pharmaceutical composition blocks calcium channels without undesirable side effects that would mask the calcium channel blocker effect.
Claim 56
Dependent Claim
35 words
An anthelmintic composition functioning as a calcium channel blocker comprising at least one toxin extracted from the venom of the Agelenopsis aperta spider having a molecular weight of from about 500 to about 1,500 daltons.
Claim 57
Dependent Claim
35 words
An anthelmintic composition functioning as a calcium channel blocker comprising at least one toxin extracted from the venom of the Agelenopsis aperta spider having a molecular weight of from about 500 to about 1,500 daltons.
Claim 58
Dependent Claim
35 words
An anthelmintic composition functioning as a calcium channel blocker comprising at least one toxin extracted from the venom of the Agelenopsis aperta spider having a molecular weight of from about 7,000 to about 10,000 daltons.
Claim 59
Dependent Claim
35 words
An anthelmintic composition functioning as a calcium channel blocker comprising at least one toxin extracted from the venom of the Agelenopsis aperta spider having a molecular weight of from about 7,000 to about 10,000 daltons.
Claim 60
Independent Claim
71 words
A method of manufacturing a calcium channel blocker comprising the steps of: (a) obtaining at least one Agelenopsis aperta spider; (b) obtaining venom from said at least one spider; (c) separating the toxins of the venom so obtained; (d) recovering an individual toxin separated from the venom; and (e) combining said isolated toxin with a pharmaceutically acceptable carrier such that the toxin is capable of functioning as a calcium channel blocker.
Claim 61
Independent Claim
71 words
A method of manufacturing a calcium channel blocker comprising the steps of: (a) obtaining at least one Agelenopsis aperta spider; (b) obtaining venom from said at least one spider; (c) separating the toxins of the venom so obtained; (d) recovering an individual toxin separated from the venom; and (e) combining said isolated toxin with a pharmaceutically acceptable carrier such that the toxin is capable of functioning as a calcium channel blocker.
Claim 62
Dependent Claim
23 words
A method as defined in claim 46 wherein the toxin recovered has a molecular weight of from approximately 200 to approximately 1,000 daltons.
Claim 63
Dependent Claim
23 words
A method as defined in claim 46 wherein the toxin recovered has a molecular weight of from about 5,000 to about 10,000 daltons.
Claim 64
Independent Claim
68 words
A method of administering a calcium channel blocker comprising the steps of: (a) obtaining a calcium channel blocker composition comprising at least one toxin isolated from the venom of the Agelenopsis aperta spider, said isolated toxin being combined with a pharmaceutically acceptable carrier such that the composition is capable of functioning as a calcium channel blocker; and (b) administering said calcium channel blocker composition to a human patient.
Claim 65
Independent Claim
68 words
A method of administering a calcium channel blocker comprising the steps of: (a) obtaining a calcium channel blocker composition comprising at least one toxin isolated from the venom of the Agelenopsis aperta spider, said isolated toxin being combined with a pharmaceutically acceptable carrier such that the composition is capable of functioning as a calcium channel blocker; and (b) administering said calcium channel blocker composition to a human patient.
References Cited (Backward Citations)
EP0156540A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-05-14 | 1993-11-13 | 1994-05-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-05-14 | 1997-11-13 | 1998-05-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-05-14 | 2001-11-13 | 2002-05-15 | $7700.00 | Window Closed / Lapsed |