# US 8,541,376 B2 · Composition comprising and method of using angiopoietin-like protein 3 ANGPTL3

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- Number: US 8,541,376 B2
- Document ID: US8541376B2
- Status: Granted
- Kind: B2
- Application number: 12/128,545
- Filed: 2008-05-28
- Published: 2009-04-16
- Granted: 2013-09-24
- Earliest claimed: 2001-11-16
- Assignees: Genentech, Inc.
- Applicants: Napoleone Ferrara; Hans-Peter Gerber; Joe Kowalski; Maria Teresa Pisabarro; Daniel Eric Sherman
- Inventors: Napoleone Ferrara; Hans-Peter Gerber; Joe Kowalski; Maria Teresa Pisabarro; Daniel Eric Sherman
- Web page: https://patentgrep.com/patent/US8541376B2

## CPC

- C07K 14/515: Angiogenesic factors; Angiogenin
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C12N 2799/022: where the vector is derived from an adenovirus
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention is directed to methods and means for making and using Angptl3 polypeptides. The invention specifically concerns the use of Angptl3 polypeptides in inducing liver regeneration and angiogenesis. Further methods include the use of Angptl3 polypeptides in the diagnosis and treatment of liver disease. Also provided herein are antibodies which bind to the polypeptides of the present invention.

## Claims

### Claim 1

A method for the treatment of acute liver disease, comprising administering to a mammalian subject in need by acute mode a therapeutically effective amount of a polypeptide comprising an amino acid sequence having at least 98% sequence identity to the human Angptl3 sequence of SEQ ID NO: 2, or an agonist antibody of the polypeptide.

### Claim 2 (depends on 1)

The method of claim 1 wherein the mammalian subject is human.

### Claim 3 (depends on 2)

The method of claim 2 wherein said polypeptide comprises amino acid regions 281-293 (P1, SEQ ID NO: 14), 442-460 (P2, SEQ ID NO: 15), and 415-430 (P3, SEQ ID NO: 17) of the human Angptl3 sequence of SEQ ID NO: 2.

### Claim 4 (depends on 2)

The method of claim 2 wherein said polypeptide comprises SEQ ID NO:28.

### Claim 5 (depends on 2)

The method of claim 2 further comprising the administration of an additional therapeutic agent.

### Claim 6 (depends on 5)

The method of claim 5 wherein said additional therapeutic agent is an angiogenic factor.

### Claim 7 (depends on 6)

The method of claim 6 wherein said angiogenic factor is vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF).

### Claim 8 (depends on 2)

(Withdrawn/previously presented): The method of claim 2 wherein said agonist antibody is an agonist antibody specifically binding Angptl3.
