# US 7,612,170 B2 · Co-stimulatory polypeptides

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- Number: US 7,612,170 B2
- Document ID: US7612170B2
- Status: Granted
- Kind: B2
- Application number: 11/332,037
- Filed: 2006-01-13
- Published: 2006-11-30
- Granted: 2009-11-03
- Earliest claimed: 2000-06-23
- Assignees: Maxygen, Inc.
- Inventors: Juha Punnonen; Alexandra L. L. Lazetic; Steven R. Leong; Jean Chia-Chun Chang
- Web page: https://patentgrep.com/patent/US7612170B2

## CPC

- C07K 14/70503: {Immunoglobulin superfamily}
- 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)
- 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)
- 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 invention provides polynucleotides and polypeptides encoded therefrom having advantageous properties, including an ability of the polypeptides to preferentially bind a CD28 or CTLA-4 receptor at a level greater or less than the ability of human B7-1 to bind CD28 or CTLA-4, or to induce or inhibit altered level of T cell proliferation response greater compared to that generated by human B7-1. The polypeptides and polynucleotides of the invention are useful in therapeutic and prophylactic treatment methods, gene therapy applications, and vaccines.

## Claims

### Claim 1

An isolated or recombinant polypeptide comprising a polypeptide sequence having at least 99% amino acid sequence identity to the polypeptide sequence of an extracellular domain of SEQ ID NO:86, wherein the polypeptide binds CTLA-4 or an extracellular domain of CTLA-4.

### Claim 2 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide has a CTLA-4/CD28 binding affinity ratio equal to or greater than the CTLA-4/CD28 binding affinity ratio of the extracellular domain of human B7-1.

### Claim 3 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide has an ability to inhibit T cell proliferation.

### Claim 4 (depends on 1)

The polypeptide of claim 1 wherein the extracellular domain of SEQ ID NO:86 comprises amino acid residues 35-242 of SEQ ID NO:86.

### Claim 5 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide comprises amino acid residues 35-242 of SEQ ID NO:86.

### Claim 6

An isolated or recombinant polypeptide comprising (i) a first polypeptide comprising a polypeptide sequence having at least 99% amino acid sequence identity to the polypeptide sequence of an extracellular domain of SEQ ID NO:86, wherein the first polypeptide has a CTLA-4/CD28 binding affinity ratio equal to or greater than the CTLA-4/CD28 binding affinity ratio of the extracellular domain of human B7-1, and (ii) a second polypeptide comprising at least a portion of an immunoglobulin (Ig) polypeptide.

### Claim 7 (depends on 6)

The polypeptide of claim 6, wherein the second polypeptide is an Ig polypeptide comprising a hinge, a CH2 domain and a CH3 domain.

### Claim 8 (depends on 7)

The polypeptide of claim 7, wherein the second polypeptide is an IgG polypeptide comprising a hinge, a CH2 domain, and a CH3 domain.

### Claim 9 (depends on 6)

The polypeptide of claim 6, wherein the polypeptide comprises amino acid residues 35-242 of SEQ ID NO:86.

### Claim 10 (depends on 6)

A multimer comprising at least two polypeptides of claim 6.

### Claim 11 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide has an enhanced binding affinity for CTLA-4 as compared to the binding affinity of human B7-1 for CTLA-4.

### Claim 12 (depends on 1)

A composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable excipient or carrier.

### Claim 13 (depends on 1)

An isolated or recombinant protein comprising the polypeptide of claim 1 and a signal peptide.

### Claim 14 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide is expressed on a cell or bound to a cell membrane.

### Claim 15

An isolated or recombinant polypeptide comprising a polypeptide sequence having at least 98% amino acid sequence identity to the polypeptide sequence of a mature domain of SEQ ID NO:86, wherein the polypeptide has a CTLA-4/CD28 binding affinity ratio equal to or greater than the CTLA-4/CD28 binding affinity ratio of the mature domain of human B7-1 or an ability to inhibit T cell proliferation.

### Claim 16 (depends on 15)

The polypeptide of claim 15, wherein the mature domain of SEQ ID NO:86 comprises amino acid residues 35-288 of SEQ ID NO:86.

### Claim 17 (depends on 15)

The polypeptide of claim 15, wherein the polypeptide comprises amino acid residues 35-288 of SEQ ID NO:86.

### Claim 18 (depends on 15)

The polypeptide of claim 15, wherein the polypeptide is expressed on a cell or bound to a cell membrane.

### Claim 19

An isolated or recombinant polypeptide comprising a polypeptide sequence having at least 98% amino acid sequence identity to the full-length polypeptide sequence of SEQ ID NO:86, wherein the polypeptide binds CTLA-4 or inhibits T cell proliferation.

### Claim 20 (depends on 19)

The polypeptide of claim 19, wherein the polypeptide has a CTLA-4/CD28 binding affinity ratio equal to or greater than the CTLA-4/CD28 binding affinity ratio of human B7-1.

### Claim 21 (depends on 19)

The polypeptide of claim 19, wherein the polypeptide comprises the full-length sequence of SEQ ID NO:86.
