Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same

• US 6,217,866 B1
• Filed: 06/07/1995
• Issued: 04/17/2001
• Est. Priority Date: 09/15/1988
• Status: Expired due to Term

• Current Assignee: Aventis Holdings Incorporated (Sanofi )
• Original Assignee: Rhone-Poulenc Rorer International Incorporated
• Inventors: Kris, Richard, South, Victoria J., Ricca, George A., Bellot, Francoise, Cheadle, Christopher, Givol, David, Schlessinger, Joseph
• Primary Examiner(s): Johnson, Nancy A.
• Application Number:
  US08/487,761
• Time in Patent Office: 2,141 Days
• Field of Search: 424/130.1, 424/138.1, 424/141.1, 424/143.1, 424/152.1, 424/155.1, 424/156.1, 530/388.1, 530/388.2, 530/388.22, 530/388.8, 530/388.85
• US Class Current: 424/143.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• 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: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators

Abstract

Hybridoma cell lines producing monoclonal antibodies specific to the human epidermal growth factor receptor are disclosed. The antibodies are capable of inhibiting the growth of human tumor cells expressing human epidermal growth factor receptors. Therapeutic uses of these monoclonal antibodies by themselves and in combination with anti-neoplastic agents are also disclosed.

Claims

1. A method for inhibiting the growth of human tumor cells that express human EGF receptors and are mitogenically stimulated by EGF, the method comprising administering an effective amount of an anti-neoplastic agent and an effective amount of a monoclonal antibody to a human cancer patient having said tumor cells;

(i) wherein said antibody binds to the extra-cellular domain of the human EGF receptor of said tumor cell;

(ii) wherein the antibody is not conjugated to the anti-neoplastic agent; and

(iii) wherein the antibody inhibit the binding of EGF to the EGF receptor.

2. A method for inhibiting the growth of human tumor cells that express human EGF receptors and are mitogenically stimulated by human EGF according to claim 1 wherein said anti-neoplastic agent is doxorubicin.

3. A method for inhibiting the growth of human tumor cells that express human EGF receptors and are mitogenically stimulated by human EGF according to claim 1 wherein said anti-neoplastic agent is cisplatin.

4. A method for inhibiting the growth of human tumor cells that express human EGF receptors and are mitogenically stimulated by human EGF according to claim 1 wherein said monoclonal antibody is 108 produced by hybridoma cell line ATCC HB 9764.

5. A method for inhibiting the growth of human tumor cells that express EGF receptors and are mitogenically stimulated by human EGF according to claim 1 wherein said monoclonal antibody is further characterized by its capability to inhibit the growth of human oral epidermoid carcinoma (KB) cells by binding to the extra-cellular domain of the human EGF receptor of said KB cells in an antigen-antibody complex.

6. A therapeutic composition comprising an amount of monoclonal antibody and an anti-neoplastic agent effective to inhibit the growth of human tumor cells that express human EGF receptors and are mitogenically stimulated by human EGF in association with a pharmaceutical carrier;

(i) wherein the antibody binds to the extracellular domain of the human EGF receptor of the tumor cells;

(ii) wherein the antibody is not conjugated to the anti-neoplastic agent; and

(iii) wherein the antibody inhibits the binding of EGF to the EGF receptor.

7. A therapeutic composition according to claim 6 wherein said anti-neoplastic agent is doxorubicin.

8. A therapeutic composition according to claim 6 wherein said anti-neoplastic agent is cisplatin.

9. A therapeutic composition according to claim 6 wherein said monoclonal antibody is 108 produced by hybridoma cell line ATCC HB 9764.