EP0259863A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Compositions for modulating the effect of TNF and IL-1
Assignee: Yeda Research and Development Co Ltd
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Filing: 1987-09-09
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Granted: —
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Expires: 2007-09-09
Abstract
Abstract This invention relates to methods for modulating the effects of TNF and IL-1, both the deleterious and the therapeutical effect of these cytokines. In case of deleterious effects, the invention provides methods for modulating the deleterious effect of TNF and/or IL-1 in mammals, by administering to a mammal sub-deleterious amounts of TNF and/or IL-1. The TNF and/or IL-1 to be modulated may be endogenous, i.e. generated in the organism in severe cases in amounts deleterious to the organism, or exogenously administered to a patient in amounts which are potentially deleterious. The compositions of the invention comprise effective amounts of TNF and/or IL-1 with at least one pharmaceutically acceptable carrier. The invention also relates to methods for monitoring the modulation of the TNF effect in patients treated with TNF and/or IL-1.
Inventors
- 👤 David Wallach
- 👤 Helmut Holtmann
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-11-06 09:49
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/52; C07K14/54; C07K14/545; A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/19; A61K38/191; A61K38/20; A61K38/2006; A61K38/21; A61P; A61P31/00; A61P31/04; A61P31/12; A61P33/00; A61P33/10; A61P35/00; A61P43/00
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
45 words
A method for modulating the deleterious effect of TNF, TNF-like peptides or derivatives thereof and/or IL-1, IL-1-like peptides, or derivatives thereof in mammals, comprising administering to said mammals sub-deleterious amounts of TNF, TNF-like peptides or derivatives thereof and/or IL-1, or IL-1-like peptides or derivatives thereof.
Claim 2
Independent Claim
45 words
A method for modulating the deleterious effect of TNF, TNF-like peptides or derivatives thereof and/or IL-1, IL-1-like peptides, or derivatives thereof in mammals, comprising administering to said mammals sub-deleterious amounts of TNF, TNF-like peptides or derivatives thereof and/or IL-1, or IL-1-like peptides or derivatives thereof.
Claim 3
Dependent Claim
14 words
A method according to claim 1 wherein the modulated TNF and/or IL-1 are endogenous.
Claim 4
Dependent Claim
24 words
A method according to claim 1 wherein the modulated TNF, TNF-like peptides or derivatives thereof, and/or IL-1, IL-1-like peptides or derivatives thereof are exogenous.
Claim 5
Independent Claim
54 words
A method according to claims 1 or 3, comprising administering to a mammal sub-deleterious amounts of TNF, TNF-like peptides or derivatives thereof, and/or IL-1, IL-1-like peptides or derivatives thereof prior to the administration of therapeutically effective but potentially deleterious amounts of TNF, TNF-like peptides or derivatives thereof, and/or IL-1, IL-1-like peptides or derivatives thereof.
Claim 6
Dependent Claim
12 words
A method according to claim 1 wherein the TNF is native TNF.
Claim 7
Dependent Claim
13 words
A method according to claim 1 wherein the TNF is a recombinant TNF.
Claim 8
Dependent Claim
11 words
A method according to claim 1 wherein the TNF is alpha-TNF.
Claim 9
Dependent Claim
11 words
A method according to claim 1 wherein the TNF is beta-TNF.
Claim 10
Dependent Claim
12 words
A method according to claim 1 wherein the IL-1 is native IL-1.
Claim 11
Dependent Claim
13 words
A method according to claim 1 wherein the IL-1 is a recombinant IL-1.
Claim 12
Dependent Claim
36 words
A method according to claim 4 wherein the therapeutically effective amounts of TNF, TNF-like peptides or derivatives thereof, and/or IL-1, IL-1-like peptides or derivative thereof, are administered in combination with effective amounts of a sensitizing agent.
Claim 13
Independent Claim
18 words
A method according to claims 1 or 4 further comprising administering to a mammal effective amounts of interferon.
Claim 14
Dependent Claim
38 words
A method according to claim 24 wherein the interferon is administered prior, or following, or simultaneously to the administration of the non-deleterious amount of TNF, TNF-like peptides or derivatives thereof, and/or IL-1, or IL-1-like peptides or derivatives thereof.
Claim 15
Dependent Claim
22 words
A method according to claim 11 wherein the sensitizing agent is a metabolic blocker, or a chemotherapeutically active drug, or actinomycin D.
Claim 16
Dependent Claim
13 words
A method according to claim 12 wherein the interferon is a native interferon.
Claim 17
Dependent Claim
13 words
A method according to claim 12 wherein the interferon is a recombinant interferon.
Claim 18
Dependent Claim
19 words
A method according to claim 15 or 16 wherein the interferon is an alpha-interferon, or beta- interferon, or gamma-interferon.
Claim 19
Independent Claim
38 words
A method according to claims 1, 3, 11 or 12 wherein the TNF, TNF-like peptides, or derivatives thereof, and/or the IL-1, IL-1-like peptide or derivatives thereof, the sensitizing agent or the interferon are targeted to a specific cell.
Claim 20
Dependent Claim
25 words
A method according to Claim 1 wherein the sub-deleterious amounts of IL-1 reduce the number of TNF receptors per cell by at least 80 percent.
Claim 21
Independent Claim
30 words
A method for monitoring the modulation of the TNF effect in a patient treated with IL-1, comprising the quantitation of the TNF receptor level in cell samples of said patient.
Claim 22
Independent Claim
30 words
A method for monitoring the modulation of the TNF effect in a patient treated with IL-1, comprising the quantitation of the TNF receptor level in cell samples of said patient.
Claim 23
Dependent Claim
14 words
A method according to claim 20 wherein the cell samples are peripheral blood leukocytes.
Claim 24
Dependent Claim
23 words
A composition comprising TNF, TNF-like peptides or derivatives thereof and IL-1, IL-1-like peptides or derivatives thereof, with at least one pharmaceutically acceptable excipient.
Claim 25
Dependent Claim
23 words
A composition comprising TNF, TNF-like peptides or derivatives thereof and IL-1, IL-1-like peptides or derivatives thereof, with at least one pharmaceutically acceptable excipient.
Claim 26
Dependent Claim
24 words
A composition according to claim 22 for modulating the effect of TNF, TNF-like peptides or derivatives thereof and/or IL-1, IL-1-like peptides or derivatives thereof.
Claim 27
Dependent Claim
25 words
A composition according to Claim 23 for modulating the deleterious effect of TNF, TNF-like peptides or derivatives thereof and/or IL-1, IL-1-like peptides or derivatives thereof.
Claim 28
Dependent Claim
16 words
A composition according to claim 24 for modulating the deleterious effect of endogenous TNF and/or IL-1.
Claim 29
Dependent Claim
26 words
A composition according to claim 24 for modulating the deleterious effect of exogenous TNF, TNF-like peptide or derivatives thereof and/or IL-1, IL-1-like peptide or derivative thereof.
Claim 30
Dependent Claim
13 words
A composition according to claim 22 for potentiating the cytotoxic effect of TNF.
Claim 31
Dependent Claim
13 words
A composition according to claim 22 for potentiating the cytotoxic effect of IL-1.
Claim 32
Dependent Claim
33 words
A composition according to claim 22 comprising TNF, TNF-like peptides or derivatives thereof, in amounts sub-deleterious to a mammal and therapeutically effective but potentially deleterious amounts of IL-1, IL-1-like peptides or derivatives thereof.
Claim 33
Dependent Claim
33 words
A composition according to claim 22 comprising IL-1, IL-1-like peptides or derivatives thereof in amounts sub-deleterious to a mammal and therapeutically effective but potentially deleterious amounts of TNF, TNF-like peptides or derivatives thereof.
Claim 34
Dependent Claim
15 words
A composition according to claims 28 or 29 wherein the composition is prepared in vivo.
Claim 35
Dependent Claim
28 words
A composition according to claim 31 prepared by administering the TNF, TNF-like peptides or derivatives thereof, prior to the administration of the IL-1, IL-1-like peptides or derivatives thereof.
Claim 36
Dependent Claim
27 words
A composition according to claim 31 prepared by administering the IL-1, IL-1-like peptides or derivative thereof prior to the administration of TNF, TNF-like peptides or derivatives thereof.
Claim 37
Dependent Claim
11 words
A composition according to claim 22 further comprising a sensitizing agent.
Claim 38
Dependent Claim
10 words
A composition according to claim 22 further comprising an interferon.
Claim 39
Dependent Claim
22 words
A composition according to claim 34 wherein the sensitizing agent is a metabolic blocker, or a chemotherapeufically active drug, or actinomycin D.
Claim 40
Dependent Claim
15 words
A composition according to claim 35 wherein the interferon is selected from alpha-, beta-and gamma-interferon.
Claim 41
Dependent Claim
13 words
A composition according to claim 37 wherein the interferon is a native interferon.
Claim 42
Dependent Claim
13 words
A composition according to claim 37 wherein the interferon is a recombinant interferon.
Claim 43
Dependent Claim
23 words
A composition according to claim 29 comprising TNF in amounts sub-deleterious to a mammal and therapeutically effective but potentially deleterious amounts of IL-1.
Claim 44
Dependent Claim
23 words
A composition according to claim 30 comprising IL-1 in amounts sub-deleterious to a mammal and therapeutically effective but potentially delaterious amounts of TNF.
Claim 45
Dependent Claim
72 words
A composition according to claim 22 comprising a sub-deleterious amount of IL-1, IL-1-like peptide or derivative thereof with at least one pharmaceutically acceptable excipient in a container (a) and a therapeutically effective but potentially deleterious amount of TNF, TNF-like peptide or derivative thereof with at least one pharmaceutically acceptable excipient in a container (b), and instructions for administering to a patient contents of container (a) prior to administering contents of container (b).
Claim 46
Dependent Claim
72 words
A composition according to claim 22 comprising a sub-deleterious amount of TNF, TNF-like peptide or derivative thereof with at least one pharmaceutically acceptable excipient in a container (a) and a therapeutically effective but potentially deleterious amount of IL-1, IL-1-like peptide or derivative thereof with at least one pharmaceutically acceptable excipient in a container (b), and instructions for administering to a patient contents of container (a) prior to administering contents of container (b).
Claim 47
Dependent Claim
79 words
A composition according to claim 22 comprising a sub-deleterious amount of IL-1, IL-1-like peptide or derivative thereof with at least one pharmaceutically acceptable excipient in a container (a) and a therapeutically effective but potentially deleterious amount of TNF, TNF-like peptide or derivative thereof and IL-1, IL-1-like peptide or derivative thereof, with at least one pharmaceutically acceptable excipient in a container (b), and instructions for administering to a patient contents of container (a) prior to administering contents of container (b).
Claim 48
Dependent Claim
79 words
A composition according to claim 22 comprising a sub-deleterious amount of TNF, TNF-like peptide or derivative thereof with at least one pharmaceutically acceptable excipient in a container (a) and a therapeutically effective but potentially deleterious amount of IL-1, IL-1-like peptide or derivative thereof, and TNF, TNF-like peptide and derivative thereof, with at least one pharmaceutically acceptable excipient in a container (b), and instructions for administering to a patient contents of container (a) prior to administering contents of container (b).
Claim 49
Dependent Claim
44 words
A composition according to any one of claims 42 to 45 further comprising a container (c) comprising interferon, accompanied by instructions for administering contents of container (c) prior to, simultaneously with or following the administering of contents of container (a) or of container (b).
Claim 50
Dependent Claim
46 words
A composition according to any one of claims 42 to 45 further comprising a container (c) comprising a sensitizing agent, accompanied by instructions for administering contents of container (c) prior to, simultaneously with or following the administering of contents of container (a) or of container (b).
Claim 51
Dependent Claim
24 words
A composition according to any one of claims 42 to 45 and 47 wherein the sensitizing agent is a metabolic blocker, or actinomycin D.
References Cited (Backward Citations)
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