Functional derivatives of ICAM-1 which are substantially capable of binding to LFA-1 but are substantially incapable of binding to MAC-1

• US 5,288,854 A
• Filed: 11/28/1990
• Issued: 02/22/1994
• Est. Priority Date: 11/28/1990
• Status: Expired due to Term

• Current Assignee: Center For Blood Research Incorporated
• Original Assignee: Center For Blood Research Incorporated
• Inventors: Diamond, Michael S., Springer, Timothy A., Staunton, Donald E.
• Primary Examiner(s): Nucker, Christine M.
• Assistant Examiner(s): CUNNINGHAM, THOMAS M
• Application Number:
  US07/618,286
• Time in Patent Office: 1,182 Days
• Field of Search: 530/350, 530/395, 530/402-403, 530/808, 530/827, 530/868, 424/88, 514/2, 514/12, 514/8, 514/885
• US Class Current: 530/395
• CPC Class Codes: 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
• CPC Class Codes: C07K 14/70525 ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 16/2821 against ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: Y10S 530/808 Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products
• CPC Class Codes: Y10S 530/827 Proteins from mammals or birds
• CPC Class Codes: Y10S 530/868 involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, or immunotolerance

Abstract

The present invention is directed to functional derivatives of ICAM-1 which are substantially capable of binding to LFA-1 but are substantially incapable of binding to MAC-1. Such functional derivatives of ICAM-1 contain an addition to, a substitution of, or an insertion of one or more amino acids within domain 3 of ICAM-1.

Claims

1. An ICAM-1 functional derivative which is substantially incapable of binding to MAC-1 but is substantially capable of binding to LFA-1, wherein said functional derivative comprises domains 1-3 of ICAM-1 and said functional derivative further contains a substitution or deletion of one or more of the amino acid residues from about residues 229 to 231 and from about 254 to 256 within domain 3 of ICAM-1 or an insertion of one or more amino acid residues within the region from about residues 229 to 231 and from about 254 to 256 within domain 3 of ICAM-1.

2. The ICAM-1 functional derivative of claim 1 wherein said functional derivative is a soluble derivative of ICAM-1.

3. The functional derivative of ICAM-1 of claims 1 or 2 wherein said functional derivative of ICAM-1 further comprises domain 4 of ICAM-1.

4. The functional derivative of ICAM-1 of claims 1 or 2, wherein said substitution is selected from the group consisting of D229QR/HLE and E254DE/KEK.

5. The functional derivative of ICAM-1 of claims 1 or 2 wherein said functional derivative of ICAM-1 further comprises domains 4 and 5 of ICAM-1.