# US 2009/0269331 A1 · Caspase-8 and inflammation, infection and wound healing

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- Number: US 2009/0269331 A1
- Document ID: US20090269331A1
- Status: Published application
- Kind: A1
- Application number: 12/306,929
- Filed: 2007-06-27
- Published: 2009-10-29
- Earliest claimed: 2006-06-28
- Assignees: Hadasit Medical Research Services and Development Ltd.; Yeda Research and Development Co. Ltd.
- Inventors: David Wallach; Rinai Abramovitch; Eitan Galun; Tehila Ben Moshe; Hila Barash
- Web page: https://patentgrep.com/patent/US20090269331A1

## CPC

- A61K 38/4873: {Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H}
- A61K 38/55: Protease inhibitors
- A61P 1/02: Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- 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 33/02: Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 15/1135: {against oncogenes or tumor suppressor genes}
- C12Y 304/22061: Caspase-8 (3.4.22.61)
- C12N 2310/11: Antisense
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention relates to the regulatory role of caspase-8 in infection by intracellular pathogen, inflammation and wound healing

## Claims

### Claim at position 1

-39. (canceled)

### Claim 40

A method for preventing and/or treating inflammation of a tissue or organ, except skin, comprising administering to a patient in need a therapeutically effective amount of at least one agent selected from: (i) caspase-8 or a mutein, isoform, fused protein, functional derivative, active fraction, circularly permutated derivative or a salt thereof, (ii) an agent capable of up-regulating caspase-8 level and/or activity; and (iii) an inhibitor of a natural inhibitor of caspase-8 level and/or activity.

### Claim 41 (depends on 40)

The method according to claim 40, wherein caspase-8 level and/or activity is down regulated in cells of the tissue or organ.

### Claim 42 (depends on 40)

The method according to claim 40, wherein inflammation develops following injury of the tissue or organ.

### Claim 43 (depends on 42)

The method according to claim 42, wherein injury is caused by the tissue or organ resection.

### Claim 44 (depends on 40)

The method according to claim 40, wherein the organ is the liver and caspase-8 level and/or activity is down regulated in hepatocytes.

### Claim 45 (depends on 44)

The method according to claim 44, for treatment and/or prevention of an inflammatory disease disorder or condition selected from hepatitis, inflammatory bowel diseases, vasculitis, joint inflammation, sinusitis, scleritis, periodontitis, cervicitis, uveitis, vulvovaginitis, conjunctivitis, alveolitis, esophagitis, acute glomerulonephritis, nephritis, acute bronchitis, acute cholecystitis, pancreatitis, and ear infection.

### Claim 46

(canceled)

### Claim 47

A method for treating an infection caused by an intracellular pathogen comprising administering to a patient in need a therapeutically effective amount of at least one agent selected from: (i) caspase-8 or a mutein, isoform, fused protein, functional derivative, active fraction, circularly permutated derivative or a salt thereof, (ii) an agent capable of up-regulating caspase-8 level and/or activity; and (iii) an inhibitor of a natural inhibitor of caspase-8 level and/or activity.

### Claim 48 (depends on 47)

The method according to claim 47, wherein the intracellular pathogen is selected from Mycobacteria, Listeria, Leishmania, Legionella, Salmonella and virus.

### Claim 49 (depends on 47)

The method according to claim 47, wherein infection develops in an organ or tissue comprising cells in which caspase-8 level and/or activity is down regulated.

### Claim 50 (depends on 47)

The method according to claim 47, wherein the organ is the liver.

### Claim 51 (depends on 47)

The method according to claim 47, wherein the cells are hepatocytes.

### Claim 52 (depends on 47)

The method according to claim 47, wherein the infection is caused by Listeria.

### Claim 53 (depends on 52)

The method according to claim 52, wherein the Listeria is Listeria monocytogenes.

### Claim 54 (depends on 47)

The method according to claim 47, wherein the intracellular pathogen is a virus.

### Claim 55

(canceled)

### Claim 56

A method for facilitating or accelerating healing of a wounded or injured tissue or organ comprising administering to a patient in need a therapeutically effective amount an inhibitor of caspase-8 level and/or activity.

### Claim 57 (depends on 56)

The method according to claim 56, wherein the wound or injury develops following a physical trauma selected from a chirurgic operation, bite, sport accident, accident, tissue or organ resection, and amputation.

### Claim 58 (depends on 57)

The method according to claim 57, wherein the wound or injury develops following tissue or organ resection.

### Claim 59 (depends on 58)

The method according to claim 58, wherein the tissue or organ is the liver.

### Claim 60 (depends on 56)

The method according to claim 56, wherein the tissue or organ is the liver.

### Claim 61 (depends on 56)

The method according to claim 56, wherein the caspase-8 inhibitor is selected from a caspase-8 specific antisense mRNA, a caspase-8 specific small interfering RNA, a caspas-8 specific antibody, and a caspase-8 inhibitory small molecule.

### Claim 62 (depends on 61)

The method according to claim 61, wherein the caspase-8 inhibitory small molecule has a molecular weight of 100 to 5,000 daltons.

### Claim 63 (depends on 61)

The method according to claim 61, wherein the caspase-8 inhibitory small molecule is Z-IETD-FMK (SEQ ID NO:4).

### Claim 64 (depends on 56)

The method according to claim 56, wherein the inhibitor of caspase-8 is administered for several hours to about 1, 2, 3 days and no more than 4 days.