US4808705A
Expired / Lapsed
US
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Stable formulations of ricin toxin a chain and of RTA-immunoconjugates and stabilizer screening methods therefor
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1986-12-19
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Granted: 1989-02-28
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Expires: 2006-12-19
Abstract
Abstract Highly stable pharmaceutical compositions suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RTA-immunoconjugate dissolved in an inert carrier method comprising a stabilizer are claimed. Screening methods for selecting stabilizers effective in preventing precipitation and aggregation of such compositions are described. Preferred stabilizers includes glycerol at a concentration (v/v) of from about 25 to about 35%; dextran sulfates having molecular weights from about 0.1×10 6 to about 2×10 6 daltons; and human serum albumin. The invention further comprises such compositions which have been lyophilized and/or reconstituted wherein the stabilizer is non-volatile, and may further comprise a carbohydrate stabilizer. The invention further comprises stabilized RTA compositions.
Inventors
- 👤 Robert Ferris
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 22:11
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/02; G01N33/14; A; A61; A61K; A61K47/00; A61K47/06; A61K47/26; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61K47/6819; A61K47/6825; A61K47/6827; A61K9/00; A61K9/0012; A61K9/0019; Y; Y10; Y10S; Y10S530/00; Y10S530/808; Y10S530/861
Claims Analysis
Total Claims: 49
Claim 1
Independent Claim
69 words
A stable lyophilized pharmaceutical composition of matter suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RTA-immunoconjugate dissolved in an inert carrier medium comprising a stabilizer that effectively prevents the precipitation and aggregation of said RTA-immunoconjugate upon resuspension and agitation after addition of a physiologically acceptable solution thereto, "wherein the stabilizer is selected from the group consisting of glycerol, albumin, and dextran sulfate."
Claim 2
Dependent Claim
69 words
A stable lyophilized pharmaceutical composition of matter suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RTA-immunoconjugate dissolved in an inert carrier medium comprising a stabilizer that effectively prevents the precipitation and aggregation of said RTA-immunoconjugate upon resuspension and agitation after addition of a physiologically acceptable solution thereto, "wherein the stabilizer is selected from the group consisting of glycerol, albumin, and dextran sulfate."
Claim 3
Dependent Claim
80 words
A stable pharmaceutical composition of matter suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RCA-immunoconjugate dissolved in an inert carrier medium comprising a stabilizer selected from the group consisting of glycerol, a dextrad sulfate having a molecular weight from about 0.1×10 6 to about 2×10 6 daltons; and human serum albumin, wherein said stabilizer is present at a concentration and amount such that the composition is resistant to aggregation and precipitation upon agitation.
Claim 4
Dependent Claim
80 words
A stable pharmaceutical composition of matter suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RCA-immunoconjugate dissolved in an inert carrier medium comprising a stabilizer selected from the group consisting of glycerol, a dextrad sulfate having a molecular weight from about 0.1×10 6 to about 2×10 6 daltons; and human serum albumin, wherein said stabilizer is present at a concentration and amount such that the composition is resistant to aggregation and precipitation upon agitation.
Claim 5
Dependent Claim
14 words
A composition according to claim 2 wherein the RTA in the RTA-immunoconjugate is srRTA.
Claim 6
Dependent Claim
11 words
A composition according to claim 3 wherein the RTA-immunoconjugate is 260F9-IT-srRTA.
Claim 7
Dependent Claim
17 words
A composition according to claim 3 wherein the stabilizer is glycerol at a concentration of about 30%.
Claim 8
Dependent Claim
26 words
A composition according to claim 2 wherein the inert carrier medium is either phosphate buffered saline or sodium phosphate at a concentration of about 0.15 M.
Claim 9
Dependent Claim
14 words
A composition according to claim 6 wherein the concentration range is about 0.1 M.
Claim 10
Dependent Claim
26 words
A composition according to claim 3 wherein the stabilizer is a dextran sulfate having a molecular weight from about 0.3×10 6 to about 1×10 6 daltons.
Claim 11
Dependent Claim
19 words
A composition according to claim 8 wherein the molecular weight of said dextran sulfate is about 0.5×10 6 daltons.
Claim 12
Dependent Claim
22 words
A composition according to claim 9 wherein the concentration range for said dextran sulfate stabilizer is from about 0.002 to about 2%.
Claim 13
Dependent Claim
15 words
A composition according to claim 10 wherein the concentration range is from 0.006 to 1.5%.
Claim 14
Dependent Claim
17 words
A composition according to claim 11 wherein the concentration range is from about 0.01 to about 1%.
Claim 15
Dependent Claim
24 words
A composition according to claim 3 wherein the stabilizer is human serum albumin at a concentration (w/v) of from about 1 to about 5%.
Claim 16
Dependent Claim
16 words
A composition according to claim 13 wherein the concentration is from about 2 to about 4%.
Claim 17
Dependent Claim
16 words
A composition according to claim 14 wherein the concentration is from about 2.5 to about 3.5%.
Claim 18
Dependent Claim
12 words
A composition according to claim 15 wherein the concentration is about 3%.
Claim 19
Dependent Claim
18 words
A composition according to claim 2 wherein the monoclonal antibody of said RTA-immunoconjugate is from the IgG class.
Claim 20
Dependent Claim
18 words
A composition according to claim 17 wherein said monoclonal antibody is from the IgG1, IgG2 or IgG3 subclass.
Claim 21
Dependent Claim
14 words
A composition according to claim 18 wherein said subclass is either IgG1 or IgG2.
Claim 22
Dependent Claim
11 words
A composition according to claim 19 wherein said subclass if IgG1.
Claim 23
Dependent Claim
11 words
A composition according to claim 2 further comprising a carbohydrate stabilizer.
Claim 24
Dependent Claim
20 words
A composition according to claim 2 wherein the RTA-immunoconjugate is in a concentration from about 0.002 to about 20 mg/ml.
Claim 25
Dependent Claim
17 words
A composition according to claim 1 wherein the stabilizer selected is non-volatile and the composition is lyophilized.
Claim 26
Dependent Claim
32 words
A composition according to claim 23 wherein the non-volatile stabilizer is either a dextran sulfate having a molecular weight from about 0.1×10 6 to about 2×10 6 daltons or human serum albumin.
Claim 27
Dependent Claim
22 words
A composition according to claim 24 wherein the stabilizer is human serum albumin at a concentration from about 1 to about 5%.
Claim 28
Dependent Claim
11 words
A composition according to claim 23 further comprising a carbohydrate stabilizer.
Claim 29
Dependent Claim
11 words
A composition according to claim 25 further comprising a carbohydrate stabilizer.
Claim 30
Dependent Claim
29 words
A composition according to claim 27 wherein said carbohydrate stabilizer is selected from the group comprising sucrose, maltose, glucose, dextrose, lactose, mannitol, sorbitol, inositol, galactitol, xylitol, mannose and fructose.
Claim 31
Dependent Claim
23 words
A composition according to claim 28 wherein the carbohydrate stabilizer is selected from the group comprising sucrose, maltose, glucose, dextrose, lactose and mannitol.
Claim 32
Dependent Claim
21 words
A composition according to claim 29 wherein the carbohydrate stabilizer is selected from the group comprising sucrose, glucose, maltose and mannitol.
Claim 33
Dependent Claim
15 words
A composition according to claim 30 wherein the carbohydrate stabilizer is either sucrose or maltose.
Claim 34
Dependent Claim
35 words
A composition according to claim 31 wherein sucrose is in the concentration range of from about 0.5 to about 10% and wherein maltose is in the concentration range of from about 0.5 to about 20%.
Claim 35
Dependent Claim
24 words
A composition according to claim 32 wherein the human serum albumin (HSA) stabilizer is in the concentration range from about 2 to about 4%.
Claim 36
Dependent Claim
21 words
A composition according to claim 33 wherein sucrose or maltose is in a concentration of from about 0.75 to about 5%.
Claim 37
Dependent Claim
21 words
A composition according to claim 34 wherein the HSA stabilizer is in a concentration of from about 2.5 to about 3.5%.
Claim 38
Dependent Claim
23 words
A composition according to claim 27 wherein the carbohydrate stabilizer is in a concentration (w/v) range of from about 1 to about 2%.
Claim 39
Dependent Claim
22 words
A composition according to claim 35 wherein either sucrose or maltose is in a concentration of from about 1 to about 2%.
Claim 40
Dependent Claim
27 words
A composition according to claim 37 wherein HSA is in a concentration of about 3% and the carbohydrate stabilizer is sucrose at a concentration of about 1%.
Claim 41
Dependent Claim
11 words
A composition according to claim 38 wherein the pH is physiologic.
Claim 42
Dependent Claim
31 words
A composition according to claim 39 wherein the inert carrier medium is either phosphate buffered saline or sodium phosphate in a molarity range of from about 0.13 to about 0.18 M.
Claim 43
Dependent Claim
22 words
A composition according to claim 40 which is reconstituted and diluted according to a clinician's decision based on a patient's therapeutic needs.
Claim 44
Dependent Claim
19 words
A composition according to claim 41 which upon reconstitution has a pH of from about 6.5 to about 8.
Claim 45
Dependent Claim
17 words
A composition according to claim 42 which has a pH of from about 7.1 to about 7.2
Claim 46
Dependent Claim
14 words
A composition according to claim 43 wherein the RTA in the RTA-immunoconjugate is srRTA.
Claim 47
Dependent Claim
11 words
A composition according to claim 44 wherein the RTA-immunoconjugate is 260F9-IT-srRTA.
Claim 48
Dependent Claim
70 words
A stable pharmaceutical composition of matter suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RTA-immunoconjugate dissolved in an inert carrier medium comprising a stabilizer that effectively prevents the precipitation and aggregation of said RTA-immunoconjugate as determined by clarity of the pharmaceutical RTA-immunoconjugate composition upon resuspension and after agitation "wherein the stabilizer is selected from the group consisting of glycerol, albumin, and dextran sulfate."
Claim 49
Dependent Claim
70 words
A stable pharmaceutical composition of matter suitable for parenteral administration to animals or humans comprising a therapeutically effective amount of an RTA-immunoconjugate dissolved in an inert carrier medium comprising a stabilizer that effectively prevents the precipitation and aggregation of said RTA-immunoconjugate as determined by clarity of the pharmaceutical RTA-immunoconjugate composition upon resuspension and after agitation "wherein the stabilizer is selected from the group consisting of glycerol, albumin, and dextran sulfate."
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-02-28 | 1992-08-29 | 1993-02-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-02-28 | 1996-08-29 | 1997-02-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-02-28 | 2000-08-29 | 2001-02-28 | $7700.00 | Window Closed / Lapsed |