Antibodies which bind a subpopulation of Mac-1 (CD11b/CD18) molecules which mediate neutrophil adhesion to ICAM-1 and fibrinogen

• US 5,877,295 A
• Filed: 08/22/1995
• Issued: 03/02/1999
• Est. Priority Date: 09/30/1992
• Status: Expired due to Term

• Current Assignee: Center For Blood Research Incorporated
• Original Assignee: The Centre for Blood Research
• Inventors: Springer, Timothy A., Diamond, Michael
• Primary Examiner(s): Feisee, Lila
• Assistant Examiner(s): Gambel, Phillip
• Application Number:
  US08/517,589
• Time in Patent Office: 1,288 Days
• Field of Search: 530/387.1, 530/388.1, 530/388.7, 530/389.6, 530/388.22, 530/388.23, 435/70.21, 435/325, 435/326, 435/343.4, 435/172.2, 435/332, 435/334, 435/343.2, 435/343, 435/346
• US Class Current: 530/388.73
• 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 14/70553 Integrin beta2-subunit-containing molecules, e.g. CD11, CD18
• CPC Class Codes: C07K 16/2845 against integrin beta2-subunit-containing molecules, e.g. CD11, CD18

Abstract

The present invention is based on the novel observation that upon stimulation of resting myeloid cells, not all of the Mac-1 molecules expressed by the cell become activated. Only select subpopulations of Mac-1 molecules are activated and become capable of binding ligand. Further, the activated Mac-1 molecules were found to possess activation specific epitopes which distinguishes them from non-activated Mac-1 molecules. Based on these observations antibodies are described which selectively bind activated Mac-1 molecules but are substantially incapable of binding non-activated Mac-1.

Claims

1. An antibody, an antigen binding antibody fragment, or an antigen binding antibody derivative, wherein said antibody, said antigen binding antibody fragment, and said antigen binding antibody derivative, blocks Mac-1/ligand interaction by selectively binding to activated Mac-1 present on stimulated myeloid cells, antibody, wherein said said antigen binding antibody fragment, and said antigen binding antibody derivitive, selectively bind to the same subpopulation of said activated Mac-1 molecules as that bound by the antibody produced by a hybridoma selected from the group consisting of ATCC Deposit HB11460 and ATCC Deposit HB11461.

2. The antibody, antigen binding antibody fragment, and the antigen binding antibody derivative of claim 1 wherein said antibody said antigen binding antibody fragment, and said antigen binding antibody derative selectively bind to said activated Mac-1, and block the binding of said stimulated myeloid cell to ICAM-1.

3. The antibody, antigen binding antibody fragment, or antigen binding antibody derivative of claim 1 wherein said antibody, said antigen binding antibody fragment, and said antigen binding antibody derivative, competitively bind with antibody produced by a hybridoma selected from the group consisting of ATCC Deposit HB11460 and ATCC Deposit HB11461 for activated Mac-1 present on stimulated myeloid cells.

4. An anti-Mac-1 antibody, wherein said antibody is CBRM 1/5 obtainable from ATCC Deposit HB11460.

5. An anti-Mac-1 antibody, wherein said antibody is CBRM 1/19 obtainable from ATCC Deposit HB11461.