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US5527692A Expired / Lapsed US ⏱️ 0.0 years remaining

Methods for producing thrombin

Assignee: International Business Machines Corp
•
Filing: 1995-06-05
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Granted: 1996-06-18
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Expires: 2015-06-05
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Abstract

Abstract Methods are disclosed for producing thrombin. The protein is produced from host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of thrombin precursors. The DNA constructs generally include the following operably linked elements: a transcriptional promoter, DNA sequence encoding a gla-domainless prothrombin, and a transcriptional terminator. Thrombin precursors produced from transformed or transfected host cells are activated either in vivo or in vitro.

Inventors

  • 👤 Richard D. Holly
  • 👤 Donald C. Foster

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-05 13:27
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6429; C07; C07K; C07K14/00; C07K14/37; C07K14/39; C12N9/6456; C12Y; C12Y304/00; C12Y304/21; C12Y304/21005; A; A61; A61K; A61K38/00; C07K2319/00; C07K2319/01; C07K2319/02

Claims Analysis

Total Claims: 14
Claim 1
Independent Claim 15 words
A pharmaceutical composition which comprises an activated recombinant gla-domainless prothrombin and a physiologically acceptable carrier.
Claim 2
Dependent Claim 15 words
A pharmaceutical composition which comprises an activated recombinant gla-domainless prothrombin and a physiologically acceptable carrier.
Claim 3
Dependent Claim 44 words
The pharmaceutical composition of claim 1, wherein the activated recombinant prothrombin is produced by cleavage of a thrombin precursor encoded by a DNA construct comprising the following operably linked elements: a transcriptional promoter, a DNA segment encoding a gla-domainless prothrombin and a transcriptional terminator.
Claim 4
Dependent Claim 39 words
The pharmaceutical composition of claim 2, wherein the promoter of the DNA construct encoding the thrombin precursor is the mouse metallothionein-1 promoter, the adenovirus major late promoter, the Saccharomyces cerevisiae TPI1 promoter or the Saccharomyces cerevisiae ADH2-4 c promoter.
Claim 5
Dependent Claim 48 words
The pharmaceutical composition of claim 2, wherein the DNA construct encoding the thrombin precursor further comprises a signal sequence selected from human tissue plasminogen activator leader sequence, the human α-2 plasmin inhibitor signal sequence, the Saccharomyces cerevisiae BAR1 secretory signal sequence or the Saccharomyces cerevisiae MFα1 signal sequence.
Claim 6
Dependent Claim 57 words
The pharmaceutical composition of claim 2, wherein the gla-domainless prothrombin comprises kringle 1, kringle 2, the A chain, an activation site and the serine protease domain of prothrombin; kringle 2, the A chain, an activation site and the serine protease domain of prothrombin; or the A chain, an activation site and the serine protease domain of prothrombin.
Claim 7
Dependent Claim 27 words
The pharmaceutical composition of claim 5, wherein the gla-domainless prothrombin activation site is cleavable by a snake venom activator, thrombin or the Saccharomyces cerevisiae KEX2 gene product.
Claim 8
Dependent Claim 15 words
The pharmaceutical composition of claim 1, wherein the recombinant gla-domainless prothrombin is human gla-domainless prothrombin.
Claim 9
Dependent Claim 15 words
The pharmaceutical composition of claim 2, wherein the recombinant thrombin precursor is human gla-domainless prothrombin.
Claim 10
Dependent Claim 9 words
The pharmaceutical composition of claim 1, further comprising fibrinogen.
Claim 11
Dependent Claim 19 words
An isolated protein which comprises recombinant human gla-domainless prothrombin that can be cleaved to form an active thrombin molecule.
Claim 12
Dependent Claim 19 words
An isolated protein which comprises recombinant human gla-domainless prothrombin that can be cleaved to form an active thrombin molecule.
Claim 13
Dependent Claim 24 words
A pharmaceutical composition which comprises recombinant human gla-domainless prothrombin that can be cleaved to form an active thrombin molecule, and a physiologically acceptable carrier.
Claim 14
Dependent Claim 24 words
A pharmaceutical composition which comprises recombinant human gla-domainless prothrombin that can be cleaved to form an active thrombin molecule, and a physiologically acceptable carrier.

References Cited (Backward Citations)

KR900005533A Cited
WO1991011519A1 Cited
EP0443724A1 Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1999-06-18 1999-12-18 2000-06-18 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 2003-06-18 2003-12-18 2004-06-18 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2007-06-18 2007-12-18 2008-06-18 $7700.00 Window Closed / Lapsed

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