US4436728A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Refined detoxified endotoxin product
Assignee: Ribi Immunochem Research Inc
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Filing: 1982-05-26
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Granted: 1984-03-13
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Expires: 2002-05-26
Abstract
Abstract A pharmaceutical composition comprising refined detoxified endotoxin, cell wall skeleton and trehalose dimycolate is disclosed which is effective for the treatment of cancerous tumors. Methods of using the composition for these purposes are also disclosed.
Inventors
- 👤 Edgar E. Ribi
- 👤 Steven M. Schwartzman
- 👤 John L. Cantrell
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 11:58
CPC Classifications
A; A61; A61K; A61K35/00; A61K35/66; A61K35/74; A61K31/00; A61K31/70; A61K31/7016; A61K47/00; A61K47/06; A61K9/00; A61K9/0012; A61K9/0019; A61K9/10; A61K9/107; A61P; A61P35/00; A61K9/14; A61K9/19; Y; Y10; Y10S; Y10S530/00; Y10S530/82; Y10S530/825
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
152 words
A therapeutic composition for imparting immunotherapy comprising an effective amount of each of (a) refined detoxified endotoxin having no detectable 2-keto-3-deoxyoctanoate and having between 350 and 475 nmoles/mg of phosphorus and between about 1700 and 2000 nmoles/mg of fatty acids prepared by the method which comprises: (i) hydrolyzing an endotoxin extract derived from Enterobacteriaciae with an acid capable of hydrolyzing the same; (ii) lyophilizing the hydrolyzed product to obtain crude lipid A; (iii) treating crude lipid A with a first solvent capable of dissolving fatty acids contained therein to remove said fatty acids from a resulting insoluble product (iv) dissolving the resulting insoluble product in a second solvent capable of dissolving the same; and (v) passing the resulting solution through a chromatographic column of a type which will allow elution of the desired product to obtain the refined detoxified endotoxin; (b) cell wall skeleton; (c) trehalose dimycolate; and a pharmaceutically acceptable carrier.
Claim 2
Dependent Claim
152 words
A therapeutic composition for imparting immunotherapy comprising an effective amount of each of (a) refined detoxified endotoxin having no detectable 2-keto-3-deoxyoctanoate and having between 350 and 475 nmoles/mg of phosphorus and between about 1700 and 2000 nmoles/mg of fatty acids prepared by the method which comprises: (i) hydrolyzing an endotoxin extract derived from Enterobacteriaciae with an acid capable of hydrolyzing the same; (ii) lyophilizing the hydrolyzed product to obtain crude lipid A; (iii) treating crude lipid A with a first solvent capable of dissolving fatty acids contained therein to remove said fatty acids from a resulting insoluble product (iv) dissolving the resulting insoluble product in a second solvent capable of dissolving the same; and (v) passing the resulting solution through a chromatographic column of a type which will allow elution of the desired product to obtain the refined detoxified endotoxin; (b) cell wall skeleton; (c) trehalose dimycolate; and a pharmaceutically acceptable carrier.
Claim 3
Dependent Claim
38 words
The composition of claim 1, wherein the effective amount of refined detoxified endotoxin and trehalose dimycolate is up to about 1500 micrograms and the effective amount of cell wall skeleton is up to about 4500 micrograms per injection.
Claim 4
Dependent Claim
12 words
The composition of claim 1 wherein the composition is in lyophilized form.
Claim 5
Dependent Claim
14 words
The composition of claim 1 is in the form of an oil droplet emulsion.
Claim 6
Dependent Claim
36 words
A method for imparting immunotherapy in a warm blooded animal having an immunogenic tumor comprising administering the composition of claim 1, 2, 3 or 4 to said warm blooded animal by injection into said immunogenic tumor.
Claim 7
Dependent Claim
49 words
The method of claim 5, further comprising administering said composition containing between about 6.25 and 250 micrograms/ml of refined detoxified endotoxin and between about 125 and 750 micrograms/ml of cell wall skeleton and between about 125 and 250 micrograms/ml of trehalose dimycolate by injection into said warm blooded animal.
Claim 8
Dependent Claim
20 words
The method of claim 6, further comprising injecting said composition directly into the tumor tissue for up to five injections.
Claim 9
Dependent Claim
17 words
The method of claim 7, wherein said injections are made at intervals of at least one week.
Claim 10
Dependent Claim
28 words
The method of claim 1, wherein the Enterobacteriaciae are selected from the group consisting of Salmonella, Shigella, Escherichia, Brucella, Bordetella, Citrobacter, Pseudomonas, pasturella, Neisseria, Proteus, Klebsiella, and Serratia.
Claim 11
Dependent Claim
29 words
The method of claim 9, wherein the Enterobacteriaciae are selected from the group consisting of S.minnesota, S.typhimurium, B.pertussis, B.abortus, S.enteritidis, E.coli, S.typhi, S.marcescens, S.typhosa, Shigella flexni, and S.abortus equi.
Claim 12
Dependent Claim
14 words
The method of claim 1, wherein the endotoxin extract is obtained by methanol-chloroform precipitation.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-03-13 | 1987-09-12 | 1988-03-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-03-13 | 1991-09-12 | 1992-03-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-03-13 | 1995-09-12 | 1996-03-13 | $7700.00 | Window Closed / Lapsed |