Anti-P-selectin antibodies

• US 20050226876A1
• Filed: 04/08/2005
• Published: 10/13/2005
• Est. Priority Date: 04/13/2004
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Parren, Paul, Steiner, Beat, Graus, Yvo, Kopetzki, Erhard, Rebers, Frank, Stubenrauch, Kay-Gunnar, Strein, Pamela, van Vugt, Martine, Himber, Jacques, Jansen-Molenaar, Miranda, Kling, Dorothee, van de Winkel, Jan, Stern, Anne
• Granted Patent: US 7,563,441 B2
• Time in Patent Office: Days
• US Class Current: 424/144.100
• 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 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/2854 against selectins, e.g. CD62
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: Y10S 435/81 Packaged device or kit

Abstract

This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).

Claims

1. An antibody containing a Fc part derived from human origin wherein the antibody binds to P-selectin and is non-binding to complement factor C1q, said antibody being selected from the group consisting of (a) human subclass IgG1 antibody comprising at least one mutation in L234, L235, D270, N297,E318, K320, K322, P331 and P329, and (b) human subclass IgG4 antibody wherein S228 is replaced by P and L235 is replaced by E.

4. A nucleic acid molecule encoding the antibody of claim 1, wherein the antibody is an antibody molecule.

5. A vector comprising the nucleic acid molecule of claim 4.

6. A host cell comprising the vector of claim 5.

11. A method for the preparation of the antibody of claim 1 comprising the host cell of claim 6 under conditions that allow synthesis and recovery of the antibody.

13. A pharmaceutical composition comprising the antibody of claim 1.

14. The pharmaceutical composition of claim 13, further comprising at least one pharmaceutically acceptable excipient.

17. A method for treatment of a patient in need of therapy comprising administering to the patient a therapeutically effective amount of the antibody of claim 1.

18. A medicament comprising the antibody of claim 1 for the treatment of inflammatory and thrombotic disorders.

19. The medicament of claim 18 wherein the inflammatory and thrombotic disorders comprise PAOD or CLI.

20. A kit to detect the presence of P-selectin protein comprising the antibody of claim 1.

21. The kit of claim 20 further comprising one or more of the group consisting the nucleic acid molecule of claim 4, the vector of claim 5 and the host cell of claim 6.

2. An anti-P-selectin antibody wherein the antibody is a human antibody which binds at least 1000 fold more specifically to P-selectin than to E- or L-selectin as measured by EC50 values in an Elisa assay, wherein the P—

, E- and L-selectin are coated onto the microtiter plate.

3. An anti-P-selectin antibody wherein the antibody is a human antibody which binds at least 1000 fold more specifically to P-selectin than to E- or L-selectin as measured by EC50 values in an Elisa assay, wherein the P- and E- or L-selectin are coated onto the microtiter plate.

7. An anti-P-selectin antibody produced by a hybridoma cell line selected from the group consisting of DSM ACC2640, DSM ACC2641 and DSM ACC2642.

8. A nucleic acid molecule encoding the antibody of claim 7, wherein the antibody is an antibody molecule.

9. A vector comprising the nucleic acid molecule of claim 8.

10. A host cell comprising the vector of claim 9.

12. A method for the preparation of the antibody of claim 7 comprising the host cell of claim 10 under conditions that allow synthesis and recovery of the antibody.

15. A pharmaceutical composition comprising the antibody of claim 7.

16. The pharmaceutical composition of claim 15, further comprising at least one pharmaceutically acceptable excipient.