# US 5,705,732 A · Universal donor cells

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- Number: US 5,705,732 A
- Document ID: US5705732A
- Status: Granted
- Kind: A
- Application number: 08/087,007
- Filed: 1993-07-01
- Granted: 1998-01-06
- Earliest claimed: 1989-06-12
- Assignees: Oklahoma Medical Research Foundation; Yale University
- Inventors: Peter J. Sims; Alfred L.M. Bothwell; Eileen A. Elliot; Richard A. Flavell; Joseph Madri; Scott Rollins; Leonard Bell; Stephen Squinto
- Web page: https://patentgrep.com/patent/US5705732A

## CPC

- A01K 67/0276: Knock-out vertebrates
- A01K 67/0278: Knock-in vertebrates, e.g. humanised vertebrates
- A61L 27/38: {containing added animal cells (organs or tissue containing native cells A61L27/36)}
- A61L 27/507: {for artificial blood vessels (apparatus for applying cells on a blood vessel prosthesis A61F2/062)}
- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/18: against material from animals or humans
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2207/15: Humanized animals
- A01K 2217/00: Genetically modified animals
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2227/105: Murine
- A01K 2267/025: Animal producing cells or organs for transplantation
- A01K 2267/0381: Animal model for diseases of the hematopoietic system
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K 2035/122: {for inducing tolerance or supression of immune responses}
- C12N 2517/02: Cells from transgenic animals
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- 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)
- 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

Genetically engineered cells are provided which can serve as universal donor cells in such applications as reconstruction of vascular linings or the administration of therapeutic agents. The cells include a coding region which provides protection against complement-based lysis, i.e., hyperacute rejection. In addition, the cell's natural genome is changed so that functional proteins encoded by either the class II or both the class I and the class II major histocompatibility complex genes do not appear on the cell's surface. In this way, attack by T-cells is avoided. Optionally, the cells can include a self-destruction mechanism so that they can be removed from the host when no longer needed.

## Claims

### Claim 1

A transgenic non-human mammal all of whose nucleated cells contain a nucleotide sequence encoding human CD59, wherein CD59 is expressed on the surface of the mammal's cells capable of expressing human CD59, in an amount effective to inhibit complement mediated damage when the cells are exposed to human blood or serum and where the cells express at least 1.times.10.sup.3 CD59 molecules per cell.

### Claim 2 (depends on 1)

The transgenic mammal of claim 1 wherein the mammal also expresses a protein inhibiting complement selected from the group consisting of CD55 and CD46.

### Claim 3 (depends on 1)

The transgenic mammal of claim 1 wherein the mammal is a pig.

### Claim 4 (depends on 1)

The transgenic mammal of claim 1 wherein the CD59 molecule comprises the amino acid residues one to seventy seven set forth in SEQ ID NO. 3.

### Claim 5 (depends on 1)

The transgenic mammal of claim 1 wherein the CD59 molecule is encoded by the nucleotide sequence set forth in SEQ ID NO. 4.