Therapeutic, IL-6 antibody kits, and process for their preparation

• US 5,559,012 A
• Filed: 07/25/1994
• Issued: 09/24/1996
• Est. Priority Date: 07/23/1993
• Status: Expired due to Term

• Current Assignee: Immunotech (Danaher Corporation)
• Original Assignee: Immunotech (Danaher Corporation)
• Inventors: Montero-Julian, Felix A., Klein, Bernard, Brailly, Herve
• Primary Examiner(s): Knode, Marian C.
• Assistant Examiner(s): LORING, SUSAN
• Application Number:
  US08/280,230
• Time in Patent Office: 792 Days
• Field of Search: 530/388.23, 435/70.21, 435/240.27
• US Class Current: 435/70.21
• 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: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 16/24 against cytokines, lymphokines or interferons
• CPC Class Codes: C07K 16/248 IL-6

Abstract

A therapeutic kit which includes at least three unlinked monoclonal antibodies for neutralizing a short life IL-6 cytokine and a method for preparing said kit.

Claims

1. A therapeutic kit for neutralizing a short life IL-6 cytokine, said cytokine being of sufficient size to comprise at least three functional antibody-binding sites, wherein said kit includes at least three unlinked individual monoclonal antibodies which have an affinity greater than 10⁹ liter/mole and bind three distinct epitopes of said cytokine, at least one of the said three monoclonal antibodies blocking the biological activity of said cytokine as evaluated in vitro with the aid of a biological assay measuring IL-6 activity.

2. The therapeutic kit, according to claim 1, wherein the monoclonal antibodies are of the IgG type.

3. The therapeutic kit, according to claim 1, wherein two of the monoclonal antibodies of the said at least three monoclonal antibodies, are capable of blocking the biological activity of said cytokine as evaluated in vitro with the aid of a biological assay measuring IL-6 activity.

4. The therapeutic kit, according to claim 1, wherein the monoclonal antibodies are partially humanized.

5. The therapeutic kit, according to claim 1, comprising the following combinations of monoclonal antibodies:

AH64, AH65 and BE4, or

AH65, BE4 and BE8, or

AH64, AH65, BE4 and BE8.

6. The process for the preparation of a kit as defined in claim 1, wherein at least three monoclonal antibodies recognizing three distinct epitopes of said IL-6 cytokine are combined, at least one of the said at least three monoclonal antibodies blocking the biological activity of said cytokine as evaluated in vitro with the aid of a biological assay measuring IL-6 activity.

7. The process according to claim 6, wherein at least three monoclonal antibodies according to the following combinations are combined:

AH64, AH65 and BE4, or

AH65, BE4 and BE8, or

AH64, AH65, BE4 and BE8.

8. The therapeutic kit, according to claim 2, wherein two of the monoclonal antibodies of the said at least three monoclonal antibodies, are capable of blocking the biological activity of said cytokine as evaluated in vitro with the aid of a biological assay measuring IL-6 activity.

9. The therapeutic kit according to claim 1, wherein said monoclonal antibodies are chimeric human-murine monoclonal antibodies comprising an antigen-binding domain of murine origin and an Fc fragment of human origin.

10. The therapeutic kit according to claim 2, wherein said monoclonal antibodies are chimeric human-murine monoclonal antibodies comprising an antigen-binding domain of murine origin and an Fc fragment of human origin.