US5288629A
Expired / Lapsed
US
⏱️ 0.0 years remaining
DNA sequence encoding Factor VII with an amino acid substitution at Avg-152
Assignee: Novo Nordisk Health Care AG
•
Filing: 1992-09-21
•
Granted: 1994-02-22
•
Expires: 2012-09-21
Abstract
Abstract Factor VII of the coagulation cascade is modified to act as an anticoagulant. Amino acid modifications are employed to produce a modified Factor VII having a substantially reduced susceptibility to activation by enzymes which typically activate wild-type Factor VII. The modified Factor VII is able to compete with wild-type Factor VII and/or VIIa for binding tissue factor, inhibiting clotting activity. As the modified Factor VII acts specifically to interrupt the coagulation cascade, pharmaceutical compositions of modified Factor VII may be administered in place of, or in conjunction with lower doses of, conventional anticoagulant therapies.
Inventors
- 👤 Kathleen L. Berkner
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 18:18
CPC Classifications
C; C12; C12N; C12N9/00; C12N9/14; C12N9/48; C12N9/50; C12N9/64; C12N9/6421; C12N9/6424; C12N9/6437; A; A61; A61P; A61P7/00; A61P7/02; C12Y; C12Y304/00; C12Y304/21; C12Y304/21021; A61K; A61K38/00
Claims Analysis
Total Claims: 9
Claim 1
Independent Claim
76 words
A polynucleotide molecule comprising two operatively linked sequence coding regions encoding, respectively, a pre-pro peptide and a gla domain of a vitamin K-dependent plasma protein, and a gla domain-less Factor VII having an amino acid substitution in the activation region, wherein said polynucleotide encodes a modified Factor VII molecule that is resistant to activation by plasma Factor Xa, as compared to wild-type Factor VIIa, and is capable of inhibiting the clotting activity of wild-type Factor VIIa.
Claim 2
Dependent Claim
76 words
A polynucleotide molecule comprising two operatively linked sequence coding regions encoding, respectively, a pre-pro peptide and a gla domain of a vitamin K-dependent plasma protein, and a gla domain-less Factor VII having an amino acid substitution in the activation region, wherein said polynucleotide encodes a modified Factor VII molecule that is resistant to activation by plasma Factor Xa, as compared to wild-type Factor VIIa, and is capable of inhibiting the clotting activity of wild-type Factor VIIa.
Claim 3
Dependent Claim
34 words
The polynucleotide molecule according to claim 1, wherein the amino acid modification in the activation region is at a cleavage site and comprises substituting Glu, Leu, Asp, Gly, or Ile for Arg 152 .
Claim 4
Dependent Claim
14 words
The polynucleotide molecule of claim 1, wherein the Factor VII is human Factor VII.
Claim 5
Dependent Claim
24 words
The polynucleotide molecule of claim 1, wherein the pre-pro peptide and gla domain are the pre-pro peptide and gla domain of human Factor VII.
Claim 6
Dependent Claim
24 words
The polynucleotide molecule of claim 1, wherein the modified Factor VII molecule encoded thereby competes with wild-type Factor VIIa for binding to tissue factor.
Claim 7
Dependent Claim
17 words
A mammalian cell line transfected with the polynucleotide molecule of claim 1, wherein said polynucleotide is DNA.
Claim 8
Dependent Claim
22 words
The transfected cell line of claim 6, wherein the cell line is a baby hamster kidney cell line or 293 cell line.
Claim 9
Dependent Claim
19 words
The transfected cell line of claim 7, wherein the cell line is BHK 570 having ATCC No. CRL 10314.
References Cited (Backward Citations)
US4775624A
Cited
US4784950A
Cited
WO1986006408A1
Cited
US4959318A
Cited
EP0255771A1
Cited
EP0296413A2
Cited
EP0370036A1
Cited
US4994371A
Cited
WO1989009612A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-02-21 | 1997-08-23 | 1998-02-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-02-21 | 2001-08-23 | 2002-02-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-02-21 | 2005-08-23 | 2006-02-22 | $7700.00 | Window Closed / Lapsed |