# US 7,407,475 B2 · Modified annexin proteins, and methods and compositions for using them

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- Number: US 7,407,475 B2
- Document ID: US7407475B2
- Status: Granted
- Kind: B2
- Application number: 11/110,306
- Filed: 2005-04-20
- Published: 2005-09-08
- Granted: 2008-08-05
- Earliest claimed: 2001-02-21
- Assignees: Alavita Pharmaceuticals, Inc.
- Inventors: Anthony Allison
- Web page: https://patentgrep.com/patent/US7407475B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A modified annexin protein, preferably annexin V, is used to prevent thrombosis without increasing hemorrhage. Annexin binds to phosphatidylserine on the outer surface of cell membranes, thereby preventing binding of the prothrombinase complex necessary for thrombus formation. It does not, however, affect platelet aggregation necessary for hemostasis. The modified annexin molecule can be a homodimer of annexin, an annexin molecule coupled to one or more polyethylene glycol chains, or an annexin molecule coupled to another protein. By increasing the molecular weight of annexin, the modified annexin is made to remain in circulation for sufficient time to provide a sustained therapeutic effect.

## Claims

### Claim 1

A pharmaceutical composition comprising a therapeutically effective amount of an isolated fusion protein and an excipient, said fusion protein consisting essentially of a first annexin V protein coupled to a second annexin V protein by a linker and wherein said first annexin V protein and said second annexin V protein independently comprise a polypeptide selected from the group consisting of:
a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3; and
b) a polypeptide comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:3, wherein the polypeptide exhibits phosphatidylserine binding activity.

### Claim 2

A pharmaceutical composition comprising a therapeutically effective amount of an isolated fusion protein and an excipient, said fusion protein consisting essentially of a first annexin V protein coupled to a second annexin V protein by a linker and wherein said first annexin V protein and said second annexin V protein independently comprise a polypeptide selected from the group consisting of:
a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3; and
b) a polypeptide comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:3, wherein the polypeptide exhibits platelet binding activity.

### Claim 3

A pharmaceutical composition comprising a therapeutically effective amount of an isolated fusion protein and an excipient, said fusion protein consisting essentially of a first annexin V protein coupled to a second annexin V protein by a linker and wherein said first annexin V protein and said second annexin V protein independently comprise a polypeptide selected from the group consisting of:
a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 3; and
b) a polypeptide comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:3, wherein the polypeptide exhibits anticoagulation activity.