Anti-CD71 monoclonal antibodies and uses thereof for treating malignant tumor cells

• US 7,736,647 B2
• Filed: 06/15/2005
• Issued: 06/15/2010
• Est. Priority Date: 06/15/2005
• Status: Expired due to Fees

• Current Assignee: Institut National De La Sante Et De La Recherche Medicale (Inserm) (Allianz Global Investors GmbH), MABLife
• Original Assignee: Institut National De La Sante Et De La Recherche Medicale (Inserm) (Allianz Global Investors GmbH), Monoclonal Antibodies Thereapeutics
• Inventors: Bensussan, Armand, Boumsell, Laurence, Kadouche, Jean
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US11/154,262
• Publication Number:
  US 20060286030A1
• Time in Patent Office: 1,826 Days
• Field of Search: 424/133.1, 424/1.49, 424/155.1, 424/178.1, 424/450, 530/388.8, 530/391.1
• US Class Current: 424/133.1
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 51/1027 against receptors, cell-surface antigens or cell-surface determinants
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/2881 against CD71
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The present invention provides novel anti-CD71 monoclonal antibodies, in particular mouse-human chimeric anti-CD71 monoclonal antibodies, advantageously associated to effector cells for triggering ADCC mechanisms. Anti-CD71 antibodies, as well as pharmaceutical compositions containing them, are useful for inhibiting proliferation and/or killing malignant tumor cells, especially metastatic cutaneous and uveal melanoma cells.

Claims

1. An anti-CD71 monoclonal antibody, or an antigen binding fragment thereof, which comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

1 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

2.

4. The anti-CD71 monoclonal antibody of claim 1, wherein the antibody, or an antigen binding fragment thereof, is a mouse-human chimeric antibody.

5. The anti-CD71 monoclonal antibody of claim 4, which comprises a human constant region amino acid sequence selected from the group consisting of a heavy chain amino acid sequence shown in SEQ ID NO:

5, a heavy chain amino acid sequence shown in SEQ ID NO;

9, and a light chain amino acid sequence shown in SEQ ID NO;

6.

6. The anti-CD71 monoclonal antibody of claim 4, which comprises a human constant region amino acid sequence selected from the group consisting of:

a heavy chain amino acid sequence encoded by the nucleotide sequence shown in SEQ ID NO;

7, a heavy chain amino acid sequence encoded by the nucleotide sequence shown in SEQ ID NO;

10 and a light chain amino acid sequence encoded by the nucleotide sequence shown in SEQ ID NO;

8.

7. The anti-CD71 monoclonal antibody according to any one of claims 1, 2, or 3, wherein the antibody is coupled to a bioactive molecule selected from the group consisting of:

toxins, cytotoxic drugs, cytolytic drugs, radioisotopes, metals, biotin, avidin, and streptavidin.

8. The anti-CD71 monoclonal antibody according to claim 7, wherein said metals are selected from the group consisting of:

radioisotopes and non-radioactive metals.

9. The anti-CD71 monoclonal antibody according to claim 7, wherein said bioactive molecule is selected from the group consisting of:

beta-, alpha-, and gamma-emitting radioisotopes.

10. The anti-CD71 monoclonal antibody of claim 7, wherein said antibody coupled to said bioactive molecule is carried by a galenic vector selected from the group consisting of:

a liposomal vector and a cationic emulsion.

11. The anti-CD71 monoclonal antibody of claim 7, wherein said monoclonal antibody is coupled to a bioactive molecule by a cleavable linker.

12. A composition comprising at least one anti-CD71 monoclonal antibody according to any one of claims 1, 2, and 3 and a pharmaceutically acceptable carrier.

2. An anti-CD71 monoclonal antibody, or an antigen fragment thereof, which comprises a heavy chain variable region encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:

3 and a light chain variable region encoded by a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO;

4.

3. An anti-CD71 monoclonal antibody which is produced by a hybridoma cell line designated BA 120 and deposited at the Collection Nationale de Cultures de Microorganismes (Institut Pasteur, Paris, France) on Jun. 14, 2005, under number CNCM I-3449, or an antigen binding fragment produced from said antibody.