Protein C or activated protein C-like molecules

Details Protein C or activated protein C-like molecules Protein C or activated protein C-like molecules

2005-08-23

2005-08-23

Weber, Jon P. (Department: 1653)

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

Blood proteins or globulins, e.g., proteoglycans, platelet...

C530S395000, C530S350000, C514S012200, C536S023500, C435S325000, C435S320100, C435S226000, C434S094000

Reexamination Certificate

active

06933367

ABSTRACT:
The present invention relates to novel conjugates between polypeptide variants of protein C and a non-polypeptide moiety, such as PEG or sugar moieties. In particular, the present invention provides novel protein C conjugates having an increased resistance to inactivation by e.g. human plasma and α1-antitrypsin. Consequently, such conjugates have an increased in vivo half-life. Preferred examples include protein C conjugates, wherein at least one additional in vivo N-glycosylation site has been introduced. The conjugates of the invention are useful for treating a variety of diseases, including septic shock.

REFERENCES:
patent: 4775624 (1988-10-01), Bang et al.
patent: 4904584 (1990-02-01), Shaw
patent: 4959318 (1990-09-01), Foster et al.
patent: 4968626 (1990-11-01), Foster et al.
patent: 4992373 (1991-02-01), Bang et al.
patent: 5041376 (1991-08-01), Gething et al.
patent: 5073609 (1991-12-01), Foster et al.
patent: 5151268 (1992-09-01), Bang et al.
patent: 5196322 (1993-03-01), Bang et al.
patent: 5225537 (1993-07-01), Foster
patent: 5270040 (1993-12-01), Bang et al.
patent: 5270178 (1993-12-01), Gerlitz et al.
patent: 5302529 (1994-04-01), Foster et al.
patent: 5358932 (1994-10-01), Foster et al.
patent: 5453373 (1995-09-01), Gerlitz et al.
patent: 5460953 (1995-10-01), Gerlitz et al.
patent: 5516650 (1996-05-01), Foster et al.
patent: 5648254 (1997-07-01), Mulvihill et al.
patent: 5753224 (1998-05-01), Foster et al.
patent: 5766921 (1998-06-01), Foster et al.
patent: 5837843 (1998-11-01), Smirnov et al.
patent: 5847085 (1998-12-01), Esmon et al.
patent: 0 370 205 (1990-05-01), None
patent: 0 575 054 (1993-12-01), None
patent: 3072877 (1991-03-01), None
patent: 08-092294 (1996-09-01), None
patent: WO 89/05824 (1989-06-01), None
patent: WO 98/44000 (1998-10-01), None
patent: WO 99/20767 (1999-04-01), None
patent: WO 00/26230 (2000-05-01), None
patent: WO 00/26354 (2000-05-01), None
patent: WO 00/54787 (2000-09-01), None
patent: WO 00/66753 (2000-11-01), None
patent: WO 0066754 (2000-11-01), None
patent: WO 01/36463 (2001-05-01), None
patent: WO 01/57193 (2001-08-01), None
patent: WO 01/59084 (2001-08-01), None
Colpitts, Tracey L. et al., “Binding of Calcium to Individual γ- Carboxyglutamic Acid Residues of Human Protein C”,Biochemistry, 1995, 34, 2424-2430.
Friedrich, Ute. et al., “Secondary Substrate-binding Exosite in the Serine Protease Domain of Activated Protein C Important for Cleavage at Arg-506 but Not as Arg-306 in Factor Va”,The Journal of Biological Chemistry, 2001, vol. 276, No. 25:23105-23108.
Friedrich, Ute et al., “Structural and Energetic Characteristics of the Heparin-binding Site in Antihrombotic Protein C”,The Journal of Biological Chemistry, 2001, vol. 276, No. 26:24122-24128.
Gale, Andrew J. et al., “The autolysis loop of activated protein C interacts with factor Va and Differentiates between the Arg506 and Arg306 cleavage sites”,Blood, 2000, vol. 96, No. 2:585-593.
Gale, Andrew J. et al., “Nonenzymatic anticoagulant activity of the mutant serine protease Ser360Ala-activated protein C mediated by factor Va”Protein Science, (1997), 6:132-140.
Geng, Jie-Ping et al., “Functional Consequences of Mutations in Amino Acid Residues that Stabilize Calcium Binding to the First Epidermal Growth Factor Homology Domain of Human Protein C”,Thrombosis and Haemostatis, (1990) 76:720-728.
Gerlitz, Bruce et al., “Mutation of Protease Domain Residues Lys37-39 in Human Protein C Inhibits Activation by the Thrombomodulin-Thrombin Complex without Affecting Activation by Free Thrombin”,The Journal of Biological Chemistry, 1996, vol. 271, No. 37:22285-22288.
Hallam, Paula J. et al., “A novel missense mutation (Thr176→lle) at the putative hinge of the neo N-terminus of activated protein C”,Hum Genet, (1995) 95:447-450.
Holly, Rick D. et al., “Resistance to inhibition by β-1Anti-Trypsin and Species Specificity of a Chimeric Human/Bovine Protein C”,Biochemistry, (1994) 33:1876-1880.
Jhingan, Ashish et al., “The Activities of Recombinant γ-Carboxyglutamic-Acid Deficient Mutants of Activated Human Protein C toward Human Coagulation Factor Va and Factor VIII in Purified Systems and in Plasma”,Biochemistry, (1994) 33:1869-1875.
McDonlad, John F. et al., “Comparison of Naturally Occuring Vitamin K-Dependent Proteins: Correlation of Amino Sequences and Membrane Binding Properties Suggests a Membrane Contact Site”,Biochemistry, (1997) 36:5120-5127.
Mesters, Rolf M. et al., “A Novel Exosite in the Light Chain of Human Activated Protein C Essential for Interaction with Blood Coagulation Factor Va”,Biochemistry, (1993) 32:12656-12663.
Mesters, Rolf M. et al., “Identification of a Sequence of Human Activated Protein C (Residues 390-404) Essential for Its Anticoagulant Activity”,The Journal of Biological Chemistry, 1991, vol. 266, No. 36:24514-24519.
Nishioka, Junji et al., “The Gla26 Residue of Protein C is Required for the Binding of Protein C to Thrombomodulin and Endothelial Cell Protein C Receptor, but not to Protein S and Factor Va”,Thrombosis and Haemostasis, (1996) 75:275-282.
Öhlin, Ann-Kristin et al., “Proteolytic Formation and Properties of a Fragment of Protein C Containing the γ-Carboxyglutamic Acid Rich Domain and the EGF-like Region”,Biochemistry, (1990) 29:644-651.
Rezaie, Alireza, R. “Role of Residue 99 at the S2 Subsite of Factor Xa and Activated Protein C in Enzme Specificity”,The Journal of Biological Chemistry, 1996, vol. 271, No. 39:23807-23814.
Rezaie, Alireza, R. “Calcium Inhibition of the activation of protein C by thrombin Role of the P3 and P3' residues”,Eur. J. Biochem., (1994) 223:575-579.
Rezaie, Alireza, R. “Vitronectin Functions as a Cofactor for Rapid Inhibition of Activated Protein C by Plasminogen Activator Inhibitor-1”,The Journal of Biological Chemistry, May 11, 2001, vol. 276, No. 19:15567-15570.
Rezaie, Alireza, R. et al., Conversion of Glutamic Acid 192 to Glutamine in Activated Protein C Changes the Substrate Specificity and Increases Reactivity toward Macromolecular Inhibitors,The Journal of Biological Chemistry, 1993, vol. 268, No. 27:19943-19948.
Rintelen, Claudia et al., “Anticoagulant Dysfunction of Human Arg352Trp-Activated Protein C Caused by Defective Factor Va Inactivation”,Thrombosis and Haemostasis, (2001) 85:274-279.
Shen, Lei et al., “Enhancing the Activity of Protein C by Mutagenesis To Improve the Membrane-Binding Site: Studies Related to Proline-10”,Biochemistry, 1997, vol. 36, No. 51:16025-16031.
Shen, Lei et al., “Enhancement of Human Protein C Function by Site-directed Mutagenesis of the γ-Carboxyglutamic Acid Domain”,The Journal of Biological Chemistry, 1998, vol. 273, No. 47:31086-31091.
Shen, Lei et al., “Interspecies Loop Grafting in the Protease Domain of Human Protein C Yielding Enhanced Catalytic and Anticoagulant Activity”,Thrombosis and Haemostasis, (1999) 82:1078-1087.
Shen, Lei et al., “Tracking Structural Features Leading to Resistance of Activated Protein C to œ1-antitrypsin”,Biochemistry, (2000) 39:2853-2860.
Thariath, Abraham et al., “Highly conserved residue arginine-15 is required for the Ca2+- dependent properties of the γ-carboxyglutamic acid domain if human anticoagulation Protein C and activated Protein C”,Biochem. J., (1997) 322:309-315.
Zhang, Li et al., “Role of Individual γ-Carboxyglutamic Acid Residues of Activated Human Protein C in Defining its In Vitro Anticoagulant Activity”,Blood, 1992, vol. 80, No. 4:942-952.
Zhang, Li et al., “The Binding Energy of Human Coagulation Protein C to Acidic Phospholipid Vesicles Contains a Major Contribution from Leucine 5 in the γ-Carboxyglutamic Acid Domain”,The Journal of Biological Chemistry, 1994, vol. 269, No. 5:3590-3595.
Zhang, Li et al

Affiliated with

Also associated with

Rating

Protein C or activated protein C-like molecules does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Protein C or activated protein C-like molecules, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Protein C or activated protein C-like molecules will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3461684