# US 5,708,147 A · Mononuclear leukocyte directed endothelial adhesion molecule associated with atherosclerosis

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- Number: US 5,708,147 A
- Document ID: US5708147A
- Status: Granted
- Kind: A
- Application number: 08/261,304
- Filed: 1994-06-16
- Granted: 1998-01-13
- Earliest claimed: 1990-03-02
- Assignees: The Brigham and Women's Hospital, Inc.
- Inventors: Michael A. Gimbrone, Jr.; Myron I. Cybulsky; Tucker Collins
- Web page: https://patentgrep.com/patent/US5708147A

## CPC

- C07K 14/70564: {Selectins, e.g. CD62}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C07K 14/70542: {CD106}
- C07K 16/2854: {against selectins, e.g. CD62}
- 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 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- 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

The invention relates to novel endothelial cell-leukocyte adhesion molecules designated ATHERO-ELAM. ATHERO-ELAM molecules are expressed on cultured endothelial cells stimulated with bacterial LPS and selectively mediate the binding of monocytes to the endothelial cells. Monoclonal antibodies specific for ATHERO-ELAM bind to vascular endothelial cells involved in early atherosclerotic lesions, but not to vascular endothelial cells from uninvolved arterial tissue. ATHERO-ELAM and antibodies directed to ATHERO-ELAM may be used in identifying early atherosclerotic lesions and in treating and preventing atherosclerosis.

## Claims

### Claim 1

A substantially purified protein comprising a mononuclear leukocyte-selective endothelial-leukocyte adhesion molecule expressed in atherosclerotic lesions having the amino acid sequence shown in Sequence ID 2, and comprising an AS-1 domain between domains 3 and 4 of said protein and wherein said protein is selected from the group consisting of:
a protein having seven immunoglobulin-like domains, and
a protein having eight immunoglobulin-like domains and wherein one of said eight domains is an AS-III domain.

### Claim 2 (depends on 1)

The protein of claim 1 wherein said ATHERO-ELAM has a molecular weight of approximately 118 kD on an SDS-polyacrylamide gel under reducing conditions.

### Claim 3 (depends on 1)

The protein of claim 1 wherein said ATHERO-ELAM has a molecular weight of approximately 98 kD on an SDS-polyacrylamide gel under reducing conditions.

### Claim 4 (depends on 1)

The protein of claim 1 wherein said protein is encoded by the nucleotide sequence as shown in Sequence ID 1.

### Claim 5

A substantially purified protein comprising an AS-1 domain between immunoglobulin-like domains 3 and 4 of a mononuclear leukocyte-selective endothelial-leukocyte molecule expressed in atherosclerotic lesions, said protein lacking transmembrane and cytoplasmic domains, wherein said protein comprises the sequence between amino acids 1 and 774 in Sequence ID 2, and wherein said protein is selected from the group consisting of:
a protein having seven immunoglobulin-like domains, and
a protein having eight immunoglobulin-like domains and wherein one of said domains is an AS-III domain.