# US 6,444,792 B1 · CTLA4-Cγ4 fusion proteins

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- Number: US 6,444,792 B1
- Document ID: US6444792B1
- Status: Granted
- Kind: B1
- Application number: 09/227,595
- Filed: 1999-01-08
- Granted: 2002-09-03
- Earliest claimed: 1996-02-02
- Assignees: Repligen Corporation
- Inventors: Gary S. Gray; Jerry Carson; Kashi Javaherian; Paul D. Rennert; Sandra Silver
- Web page: https://patentgrep.com/patent/US6444792B1

## CPC

- C07K 14/70503: {Immunoglobulin superfamily}
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- 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 2039/5154: {Antigen presenting cells [APCs], e.g. dendritic cells or macrophages}
- C07K 2319/00: Fusion polypeptide
- 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)

## Abstract

CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cells to thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.

## Claims

### Claim 1

A CTLA4-immunoglobulin fusion protein, comprising:
a) a first peptide having at least one CTLA4 activity and a second peptide, wherein the second peptide comprises:
i) an immunoglobulin constant region, wherein the immunoglobulin constant region comprises:
1) the CH1 domain, hinge region, CH2 domain, and CH3 domain from a Cγ4 heavy chain; and
2) a Leu to Glu substitution at position 235, and a Gly to Ala substitution at position 237 of the Cγ74 heavy chain.