Peptides and methods of use

Patent metadata

Field	Value
Publication number	US-9447147-B2
Application number	US-201514634028-A
Country	US
Kind code	B2
Filing date	Feb 27, 2015
Priority date	Feb 28, 2014
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The invention provides peptides, including peptides that bind and, optionally, inhibit Protein S, and compositions thereof. The peptides may be used to, e.g., inhibit Protein S activity, enhance thrombin formation in a subject, increase blood clot formation in a subject, treat a blood coagulation disorder in a subject, purify Protein S, and identify a Protein S binding compound.

First claim

What is claimed is:

1. A peptide comprising an amino acid sequence at least 50% identical to the amino acid sequence EYYVSAGWYDYNTDTYYEFE (SEQ ID NO: 2924) and having the structure:
X1001-X1002-X1003-X1004-X1005-X1006-X1007-X1008-X1009-X1010-X1011-X1012-X1013-X1014-X1015-X1016-X1017-X1018-X1019-X2020,
wherein X1001 is A, Bpa, C, D, E, e, F, G, H, I, K, L, M, N, P, p, Q, R, S, T, V, W, or Y;
wherein X1002 is A, C, D, E, F, G, H, I, K, L, M, N, P, p, Q, R, S, T, V, W, Y, or y;
wherein X1003 is A, C, D, E, F, G, H, I, K, L, M, N, P, p, Q, R, S, T, Tle, V, W, Y, or y;
wherein X1004 is F, I, L, Tle, V, or W;
wherein X1005 is A, E, F, G, H, I, K, L, M, R, S, T, V, W, or Y;
wherein X1006 is A, F, G, I, L, Tle V, W, or Y;
wherein X1007 is G or a;
wherein X1008 is F, 1Ni, 2Ni, Bta, or W;
wherein X1009 is F or Y;
wherein X1010 is D, E, F, H, I, K, L, N, Q, V, W, or Y;
wherein X1011 is F, G, I, K, L, M, R, T, V, W, or Y;
wherein X1012 is A, D, E, F, G, H, I, K, L, N, Q, R, S, T, V, or Y;
wherein X1013 is D, E, F, G, H, I, K, L, Q, R, S, T, V, or W;
wherein X1014 is D, E, or H;
wherein X1015 is D, E, H, I, K, M, Q, R, S, T, V, or W;
wherein X1016 is F, H, W, or Y;
wherein X1017 is D, E, G, H, I, T, W, or Y;
wherein X1018 is A, D, E, G, H, I, K, L, M, P, Q, R, S, T, V, or W;
wherein X1019 is F or W; and
wherein X2020 is A, C, D, E, e, F, G, H, I, K, L, M, N, P, p, Q, R, S, T, V, W, or Y.

2. The peptide of claim 1 , wherein X1004 is V, X1005 is S, X1006 is A, X1007 is G, X1008 is W, and X1009 is Y.

3. The peptide of claim 1 comprising an amino acid sequence at least about 80% identical to the amino acid sequence EYYVSAGWYDYNTDTYYEFE (SEQ ID NO: 2924).

4. The peptide of claim 3 , wherein the amino acid sequence comprises the amino acid sequence EYYVSAGWYDYNTDTYYEFE (SEQ ID NO: 2924).

5. The peptide of claim 1 ,
wherein X1003 is A, E, F, G, H, I, K, L, N, P, R, T, V, W, y, or Y; and
wherein X1002 is A, D, E, F, G, H, I, K, L, N, P, R, T, V, W, y, or Y.

6. The peptide of claim 1 comprising an amino acid sequence at least about 90% identical to the amino acid sequence EYYVSAGWYDYNTDTYYEFE (SEQ ID NO: 2924).

7. A peptide consisting of an amino acid sequence at least about 80% identical to EYYVSAGWYDYNTDTYYEFE (SEQ ID NO: 2924).

8. The peptide of claim 1 , wherein the peptide is conjugated to a polyethylene glycol (PEG) moiety, albumin, an antibody or fragment thereof, hydroxyethyl starch, a proline-alanine-serine multimer, a C12-C18 fatty acid, or polysialic acid.

9. The peptide of claim 1 , wherein the peptide is conjugated or attached to a moiety selected from the group consisting of Bpa, Bpa-K(Bio)-C, C(Atf-Bio), C(Atf-LC-Bio), C(FeBABE), C(MalCy5), C(NEM), C(PEG), K, K(Ac), K(Ttds), K(Ttds-γGlu), T, Ttds, or Ttds-K(Bio).

Assignees

• Baxter Int
• Baxter Healthcare Sa
• Baxalta GmbH
• Baxalta Inc

Inventors

• Dockal Michael
• Polakowski Thomas
• Osterkamp Frank
• Hartmann Rudolf
• Paschke Matthias
• Hartlieb Bettina
• Scheiflinger Friedrich

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K14/745

  Blood coagulation or fibrinolysis factors · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K38/00 Primary

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K38/36

  Blood coagulation or fibrinolysis factors · CPC title