# US 7,407,771 B2 · Cash (caspase homologue) with death effector domain, modulators of the function of FAS receptors

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- Number: US 7,407,771 B2
- Document ID: US7407771B2
- Status: Granted
- Kind: B2
- Application number: 10/998,582
- Filed: 2004-11-30
- Published: 2005-07-14
- Granted: 2008-08-05
- Earliest claimed: 1997-03-03
- Assignees: Yeda Research and Development Co. Ltd.
- Inventors: David Wallach; Yura Goltsev; Andrei Kovalenko; Eugene Varfolomeev; Vadim Brodianski
- Web page: https://patentgrep.com/patent/US7407771B2

## CPC

- C12N 9/6475: {Interleukin 1-beta convertase-like enzymes (3.4.22.10; 3.4.22.36; 3.4.22.63)}
- A61K 38/00: 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)
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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

Proteins capable of modulating or mediating the function of MORT-1 are disclosed. Also disclosed are DNA sequences encoding these proteins, the recombinant production of these proteins as well as their use.

## Claims

### Claim 1

A method for inhibiting the induction of cell death in vitro, comprising treating cells with a G1 protein comprising the amino acid sequence of SEQ ID NO:4 to inhibit the induction of cell death, said G1 protein being capable of binding to or interacting directly with MORT-1 and/or any of the MORT-1-binding proteins, wherein said treating of said cells comprises introducing into said cells said G1 protein in a form suitable for intracellular introduction thereof, or introducing into said cells a nucleotide sequence encoding said G1 protein in the form of a suitable vector carrying said sequence, said vector capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, thereby inhibiting the induction of cell death.

### Claim 2

A method for inhibiting the cell death-inducing effect of FAS-R ligand or TNF in vitro on cells comprising a FAS-R or p55 TNF-R, comprising treating cells comprising a FAS-R or p55 TNF-R with a G1 protein comprising the amino acid sequence of SEQ ID NO:4 to inhibit the cell death-inducing effect of FAS-R ligand or TNF on cells comprising a FAS-R or p55-TNF-R, wherein said G1 protein is capable of binding directly to MORT-1, and/or to any of the MORT-1-binding proteins, which MORT-1 binds to the intracellular domain of FAS-R, or is capable of binding directly to MORT-1 which binds to TRADD which binds to the intracellular domain of p55 TNF-R and thereby being capable of inhibiting the activity of said FAS-R or p55 TNF-R, wherein said treating of said cells comprises introducing into said cells said G1 protein in a form suitable for intracellular introduction thereof, or introducing into said cells a DNA sequence encoding said G1 protein in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, thereby inhibiting the cell death-inducing effect of Fas-R ligand or TNF on cells comprising a FAS-R or p55 TNF-R.

### Claim 3

A method for inhibiting the induction of cell death in vitro, comprising treating cells with a G1 protein comprising the amino acid sequence of SEQ ID NO:4 to inhibit the induction of cell death, said G1 protein being capable of binding to or interacting directly with MORT-1 and/or any of the MORT-1-binding proteins, and being capable of inhibiting cell-death inducing effect of the FAS-R or p55-TNF-R, thereby inhibiting the induction of cell death.

### Claim 4

A method of inhibiting apoptotic processes or programmed cell death processes in vitro, comprising treating cells with a G1 protein comprising the amino acid sequence of SEQ ID NO:4 to inhibit apoptotic processes or programmed cell death processes, wherein said G1 protein is capable of binding directly or indirectly to MORT-1, and/or any of the MORT-1-binding proteins, which MORT-1 binds to the intracellular domain of FAS-R, or is capable of binding directly to MORT-1 and/or any of the MORT-1-binding proteins, which MORT-1 binds to TRADD which binds to the intracellular domain of p55 TNF-R, wherein said treating of said cells comprises introducing into said cells said G1 protein in a form suitable for intracellular introduction thereof, or introducing into said cells a DNA sequence encoding said G1 protein in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells, thereby inhibiting apoptotic processes or programmed cell death processes.