# US 2014/0194600 A1 · Use of anti-factor xi antibodies for prevention of thrombus formation

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- Number: US 2014/0194600 A1
- Document ID: US20140194600A1
- Status: Published application
- Kind: A1
- Application number: 14/034,738
- Filed: 2013-09-24
- Published: 2014-07-10
- Earliest claimed: 2008-06-19
- Assignees: Prothix B.V.
- Applicants: Prothix B.V.
- Inventors: Erik HACK
- Web page: https://patentgrep.com/patent/US20140194600A1

## CPC

- C07K 16/36: against blood coagulation factors
- 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 2039/505: {comprising antibodies}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention relates to binding molecules such as antibodies that specifically bind plasma coagulation factor XI and that inhibit factor XI activation and/or activity. The factor XI-binding molecules of the invention may used in methods for preventing or treating diseases, disorders and/or conditions that are mediated by factor XI activation and/or wherein inhibition of factor XI has a beneficial effect.

## Claims

### Claim 1

An antibody or a factor XI-binding fragment thereof that binds factor XI at or near the active site located in the light chain region of activated factor XI and inhibits factor XI activity,
wherein, when administered to a subject in an effective amount, said antibody or fragment treats or attenuates a disease, disorder or condition for which inhibition of factor XI has a beneficial effect.

### Claim 2 (depends on 1)

The antibody or fragment according to claim 1 that preferentially binds to the activated form of factor XI.

### Claim 3 (depends on 1)

The antibody or fragment according to claim 1 that prevents activation of substrate factor IX by factor XIa.

### Claim 4 (depends on 1)

The antibody or fragment according to claim 1 that prevents activation of substrate factor XI by factor XIa.

### Claim 5 (depends on 1)

The antibody or fragment according to claim 1 that prevents the conversion of a chromogenic substrate to a colored product by factor XIa.

### Claim 6 (depends on 1)

The antibody or fragment according to claim 1, that is a monoclonal antibody or a factor XI-binding fragment thereof.

### Claim 7 (depends on 1)

The antibody or fragment according to claim 1, that treats or attenuates said disease, disorder or condition when administered at a dosage equivalent to 0.5-20 mg of IgG per kg body weight of the subject.

### Claim 8 (depends on 1)

The antibody or fragment according to claim 1, that treats or attenuates said disease, disorder or condition when administered at a dosage that yields a molar ratio in serum that is less than or equal to 4 moles of factor XI binding sites of antibody or fragment to 1 mole of factor XI,
wherein the antibody or fragment has an affinity for factor XI characterized by a Kd that is less than or equal to 1 nM.

### Claim 9 (depends on 1)

The antibody or fragment according to claim 1, wherein the disease, disorder or condition is a thrombo-embolic disease.

### Claim 10 (depends on 9)

The antibody or fragment according to claim 9, wherein the thrombo-embolic disease is ischemic stroke, cardio-embolism, vascular access thrombosis, deep venous thrombosis, diffuse intravascular coagulation, sepsis, or septic shock.

### Claim 11 (depends on 1)

The antibody or fragment according to claim 1, that treats or attenuates said disease, disorder or condition when administered intravenously, intramuscularly or subcutaneously.

### Claim 12 (depends on 11)

The antibody or fragment according to claim 11, that treats or attenuates said disease, disorder or condition when administered intravenously as a bolus infusion or as a continuous infusion over up to 24 hours.

### Claim 13 (depends on 1)

The antibody or fragment according to claim 1, that has a half life of at least 6 days when administered to the subject and an affinity for factor XI characterized by a Kd that is less than 1 nM.