Antibodies with enhanced antibody-dependent cellular cytotoxicity activity, methods of their production and use

• US 20080118501A1
• Filed: 10/23/2006
• Published: 05/22/2008
• Est. Priority Date: 10/21/2005
• Status: Abandoned Application

• Current Assignee: LFB USA, Inc. (Agence des Participations de l’Etat), Genzyme Corporation (Sanofi )
• Original Assignee: GTC Biotherapeutics, Inc.
• Inventors: Edmunds, Timothy, McPherson, John, Meade, Harry M., Schindler, Daniel
• Application Number:
  US11/586,431
• Publication Number:
  US 20080118501A1
• Time in Patent Office: Days
• US Class Current: 424/132.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/04 from milk
• CPC Class Codes: C07K 16/283 against Fc-receptors, e.g. CD16, CD32, CD64 CD23 C07K16/2851
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/12 isolated from milk
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/732 : Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 : Complement-dependent cytotoxicity [CDC]

Abstract

The invention relates, in part, to antibodies with increased ADCC activity. Methods of producing such antibodies are also provided. The antibodies of the invention are produced in mammary epithelial cells, such as those in a non-human transgenic animal engineered to express and secrete the antibody in its milk. The antibodies or compositions comprising the antibodies can be used to treat disease in which ADCC activity provides a benefit. In one embodiment, therefore, the antibodies or compositions comprising the antibodies can be used to treat cancer, lymphoproliferative disease or autoimmune disease.

Claims

1. A composition comprising milk-derived antibodies, wherein the milk-derived antibodies have enhanced antibody-dependent cellular cytotoxicity (ADCC) activity.

29. A method of treating a subject, comprising:

administering to a subject in need thereof the composition of claim 1 in an amount effective to enhance ADCC in the subject.

30. A method of treating a subject, comprising:

administering to a subject with a disease the composition of claim 1 in an amount effective to treat the disease.

2-28. -28. (canceled)

31-39. -39. (canceled)

40. A method for enhancing the ADCC activity of an antibody or antibodies, comprising:

modifying the glycosylation of the antibody or antibodies, wherein the glycosylation is modified by producing the antibody or antibodies in mammalian mammary epithelial cells.

41-53. -53. (canceled)

54. A method, comprising:

(a) collecting the antibody from the milk of a transgenic non-human mammal engineered to express the antibody in its milk; and

(b) determining the ADCC activity of the antibody.

55-56. -56. (canceled)

57. A method for producing an antibody, comprising:

(a) collecting the antibody from mammary epithelial cells engineered to express the antibody; and

(b) determining the ADCC activity of the antibody.

58. (canceled)

59. A composition comprising mammary epthelial cell-derived antibodies, wherein the antibodies have enhanced antibody-dependent cellular cytotoxicity (ADCC) activity.

60-97. -97. (canceled)