Antibody composition-containing medicament

• US 20040109865A1
• Filed: 04/09/2003
• Published: 06/10/2004
• Est. Priority Date: 04/09/2002
• Status: Active Grant

• Current Assignee: Kyowa Kirin Co., Ltd. (Kirin Holdings Company Limited)
• Original Assignee: Kyowa Hakko Kogyo Company Limited (Kirin Holdings Company Limited)
• Inventors: Shitara, Kenya, Niwa, Rinpei
• Granted Patent: US 7,691,568 B2
• Time in Patent Office: Days
• US Class Current: 424/155.1
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

A medicament for treating a patient who cannot be cured with a medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α-bond in a complex N-glycoside-linked sugar chain, which comprises as an active ingredient an antibody composition produced by a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α-bond in a complex N-glycoside-linked sugar chain, and a method for screening the patient by using the medicament.

Claims

1. A medicament for treating a patient who cannot be cured with a medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain, which comprises as an active ingredient an antibody composition produced by a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain.

2. The medicament according to claim 1, wherein the patient who cannot be cured with a medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain is a patient in which an antigen which is recognized by the antibody composition is expressed in such an amount that the antibody composition cannot exert sufficient therapeutic effect.

3. The medicament according to claim 2, wherein the amount that the antibody composition cannot exert sufficient therapeutic effect is such an amount that the antibody composition cannot exert sufficient antibody-dependent cell-mediated cytotoxic activity.

7. The medicament according to any one of claims 1 to 6, wherein the cell resistant to a lectin is a cell having a protein selected from the group consisting of the following (a), (b) and (c):

(a) an enzyme protein relating to synthesis of an intracellular sugar nucleotide, GDP-fucose;

(b) an enzyme protein relating to modification of a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain; and

(c) a protein relating to transport of an intracellular sugar nucleotide, GDP-fucose to the Golgi body,

wherein the activity of the protein is decreased or deleted.

8. The medicament according to any one of claims 1 to 7, wherein the lectin is at least one lectin selected from the group consisting of the following (a) to (d):

(a) a Lens culinaris lectin;

(b) a Pisum sativum lectin;

(c) a Vicia faba lectin; and

(d) an Aleuria aurantia lectin.

9. The medicament according to any one of claims 1 to 8, wherein the cell is selected from the group consisting of a yeast, an animal cell, an insect cell and a plant cell.

10. The medicament according to any one of claims 1 to 9, wherein the cell is selected from the group consisting of the following (a) to (j):

(a) a CHO cell derived from a Chinese hamster ovary tissue;

(b) a rat myeloma cell line YB2/3HL.P2.G11.16Ag.20 line;

(c) a mouse myeloma cell line NS0 cell;

(d) a mouse myeloma cell line SP2/0-Ag14 cell,

(e) a BHK cell derived from a Syrian hamster kidney tissue,

(f) a hybridoma cell,

(g) a human leukemic cell line Namalwa cell;

(h) an embryonic stem cell;

(i) a fertilized egg cell, and

(j) a plant cell.

11. The medicament according to any one of claims 1 to 10, wherein the antibody molecule is selected from the group consisting of the following (a) to (d):

(a) a human antibody,

(b) a humanized antibody,

(c) an antibody fragment comprising the Fc region of (a) or (b); and

(d) a fusion protein comprising the Fc region of (a) or (b).

12. The medicament according to claim 11, wherein the antibody molecule belongs to an IgG class.

13. The medicament according to any one of claims 1 to 12, wherein the antibody composition produced by a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain is an antibody composition having a higher antibody-dependent cell-mediated cytotoxic activity than the antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain.

14. The medicament according to claim 13, wherein the higher antibody-dependent cell-mediated cytotoxic activity-having antibody composition has complex N-glycoside-linked sugar chains bound to Fc regions included in the antibody compositions, and the ratio of sugar chains in which fucose is not bound to N-acetylglucosamine in its reducing end to the total complex N-glycoside-linked sugar chains is higher than that of the antibody composition produced by a cell unresistant to a lectin which recognized a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain.

15. The medicament according to claim 14, wherein the sugar chain in which fucose is not bound is a complex N-glycoside-linked sugar chain in which 1-position of the fucose is not bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond.

16. The medicament according to any one of claims 13 to 15, wherein the antibody composition having a higher antibody-dependent cell-mediated cytotoxic activity is an antibody composition wherein the ratio of sugar chains in which fucose is not bound to N-acetylglucosamine in the reducing end to the total complex N-glycoside-linked sugar chains bound to the Fc region in the antibody composition is 20% or more.

17. The medicament according to claim 16, wherein the antibody composition in which the ratio of sugar chains in which fucose is not bound to N-acetylglucosamine in the reducing end is 20% or more is an antibody composition produced by a CHO cell.

18. The medicament according to any one of claims 1 to 17, which is a !diagnostic agent, an preventing agent or a treating agent for tumor-accompanied diseases, allergy-accompanied diseases, inflammatory-accompanied diseases, autoimmune diseases, cardiovascular diseases, viral infection-accompanied diseases or bacterial infection-accompanied diseases.

19. Use of an antibody composition produced by a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain for the manufacture of the medicament according to any one of claims 1 to 17.

20. A method for screening a patient to whom the medicament according to any one of claims 1 to 17 is effective, which comprises (i) contacting a medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain or the medicament according to any one of claims 1 to 17, with a target cell for the medicaments obtained from a patient,

(ii) measuring the activity of each of the medicaments reacted with the target cell;

(iii) comparing the activity of the medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain with the activity of the medicament according to any one of claims 1 to 17; and

(iv) selecting a patient in which the activity of the medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6 position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain is lower.

21. The method according to claim 20, wherein the method for measuring the activity of the medicament reacted with the target cell is a method selected from the group consisting of (a) to (d):

(a) an antibody-dependent cell-mediated cytotoxic activity;

(b) an Fcγ

receptor IIIa binding activity,

(c) a complement-dependent cytotoxic activity; and

(d) a growth inhibition activity.

4. A medicament for treating a disease which cannot be cured with a medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain, which comprises as an active ingredient an antibody composition produced by a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain.

5. The medicament according to claim 4, wherein the disease which cannot be cured with a medicament comprising as an active ingredient an antibody composition produced by a cell unresistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through α

-bond in a complex N-glycoside-linked sugar chain is a disease in which an antigen which is recognized by the antibody composition in a target cell relating to the disease is expressed in such an amount that the antibody composition cannot exert sufficient therapeutic effect.

6. The medicament according to claim S, wherein the amount that the antibody composition cannot exert sufficient therapeutic effect is such an amount that the antibody composition cannot exert a sufficient antibody-dependent cell-mediated cytotoxic activity.