US4892827A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Recombinant pseudomonas exotoxins: construction of an active immunotoxin with low side effects
Assignee: United States Department of Health and Human Services
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Filing: 1986-09-24
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Granted: 1990-01-09
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Expires: 2006-09-24
Abstract
Abstract Modified Pseudomonas exotaxins which comprise deletions in at least domain 1A are taught. The toxins exhibit reduced cytotoxicity.
Inventors
- 👤 Ira H. Pastan
- 👤 Sankar Adhya
- 👤 David FitzGerald
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:33
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/62; A; A61; A61K; A61K39/00; A61K39/385; A61K47/00; A61K47/50; A61K47/51; A61K47/68; A61K47/6801; A61K47/6803; A61K47/6811; A61K47/6817; A61K47/6829; A61K47/6835; A61K47/6849; A61P; A61P31/00; A61P31/04; A61P35/00; C07; C07K; C07K14/00; C07K14/195; C07K14/21; C07K14/435; C07K14/475; C07K14/495; C07K14/52; C07K14/54; C07K14/55; C07K16/00; C07K16/18; C07K16/28; C07K16/2866; C07K16/2896; A61K2039/60; A61K2039/6031; A61K2039/6037; A61K38/00; C07K2319/00; C07K2319/01; C07K2319/02; C07K2319/33; C07K2319/55
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
65 words
A modified Pseudomonas exotoxin which comprises ADP ribosylating activity and the ability to translocate across a cell membrane; wherein the exotoxin comprises a deletion in the receptor binding domain Ia of the native toxin sufficient to render the modified toxin less toxic to human or animal cells in vitro and less toxic to the liver when administered in vivo relative to an unmodified Pseudomonas exotoxin.
Claim 2
Dependent Claim
65 words
A modified Pseudomonas exotoxin which comprises ADP ribosylating activity and the ability to translocate across a cell membrane; wherein the exotoxin comprises a deletion in the receptor binding domain Ia of the native toxin sufficient to render the modified toxin less toxic to human or animal cells in vitro and less toxic to the liver when administered in vivo relative to an unmodified Pseudomonas exotoxin.
Claim 3
Dependent Claim
31 words
The modified exotoxin of claim 1, being covalently bound to a cell recognition protein which binds to a receptor on the targeted cell membrane and selectively kills cells bearing said receptor.
Claim 4
Dependent Claim
12 words
A composition comprising a cytotoxic amount of the exotoxin of claim 2.
Claim 5
Dependent Claim
56 words
A method for achieving targeted cytotoxicity, comprising contacting cells targeted to be killed, with a cytotoxic amount of the composition of claim 3, said targeted cells being those having receptors to which said recognition protein binds, but the composition being without cytotoxicity to cells which comprise PE receptors and lack receptors for the cell recognition protein.
Claim 6
Dependent Claim
29 words
The modified exotoxin of claim 2 wherein said cell recognition protein is selected from the group consisting of an antibody, a peptide hormone, a growth factor and a cytokine.
Claim 7
Dependent Claim
13 words
The exotoxin of claim 5 wherein said cell recognition protein is an antibody.
Claim 8
Dependent Claim
11 words
The exotoxin of claim 5 wherein said growth factor is a-TGF.
Claim 9
Dependent Claim
10 words
The exotoxin of claim 5 wherein said cytokine is interleukin-2.
Claim 10
Dependent Claim
12 words
The exotoxin of claim 6 wherein said antibody is antitransferin receptor antibody.
Claim 11
Dependent Claim
27 words
The modified exotoxin of claim 1 produced by employing the plasmid of ATCC deposit number 67206, 67207, or 67208 under conditions permissive for expression of the toxin.
References Cited (Backward Citations)
US4545985A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-01-08 | 1993-07-10 | 1994-01-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-01-08 | 1997-07-10 | 1998-01-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-01-08 | 2001-07-10 | 2002-01-09 | $7700.00 | Window Closed / Lapsed |