Methods of treating neoplastic, autoimmune and inflammatory diseases

• US 7,695,716 B2
• Filed: 04/11/2008
• Issued: 04/13/2010
• Est. Priority Date: 11/02/2006
• Status: Active Grant

• Current Assignee: Seagen Inc. (Pfizer Inc.)
• Original Assignee: Seattle Genetics Incorporated (Pfizer Inc.)
• Inventors: Risdon, Grant, Sievers, Eric, Wahl, Alan, Sutherland, May Kung, Lewis, Tim, Drachman, Jonathan G.
• Primary Examiner(s): Canella; Karen A
• Application Number:
  US12/101,785
• Publication Number:
  US 20080267960A1
• Time in Patent Office: 732 Days
• Field of Search: None
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]

Abstract

Methods of treating cancer and autoimmune and inflammatory diseases are provided.

Claims

1. A method of treating a patient having acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 1.5 to about 12 mg/kg body weight, whereby progression of the AML or MDS is inhibited, and wherein the AML is resistant to chemotherapy.

2. The method of claim 1, wherein the AML is multidrug resistant.

3. A method of treating a patient having AML or MDS, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 1.5 to about 12 mg/kg body weight, whereby progression of the AML or MDS is inhibited, and wherein the humanized M195 antibody is administered in combination with at least one chemotherapeutic agent effective against cancer.

4. The method of claim 3, wherein the chemotherapeutic agent is Velcade®

(bortezomib), Revlimid®

(lenalidomide), Vidaza®

(azacytidine), Dacogen®

(Decitabine) or cytarabine.

5. The method of claim 4, wherein the chemotherapeutic agent is Revlimid®

(lenalidomide).

6. The method of claim 4, wherein the chemotherapeutic agent is Vidaza®

(azacytidine).

7. The method of claim 4, wherein the chemotherapeutic agent is cytarabine.

8. A method of treating a patient having AML or MDS, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 1.5 to about 12 mg/kg body weight, whereby progression of the AML or MDS is inhibited, and wherein the AML or MDS is CD33-negative.

9. A method of treating a patient having AML or MDS, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 1.5 to about 12 mg/kg body weight,

whereby progression of the AML or MDS is inhibited,

wherein the humanized M195 antibody decreases the number of involved non-malignant effector cells, and/or decreases the levels of one or more inflammatory cytokines, chemokines or growth factors, in the patient, and

the method further comprises monitoring the levels of one or more inflammatory cytokines, chemokines or growth factors in the patient.

10. The method of claim 9, wherein the one or more inflammatory cytokines, chemokines or growth factors are interleukin-1β

(IL-1β

), tumor necrosis factor-α

(TNF-α

), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ

(IFN-γ

), vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-1 (MCP-1), RANTES, interleukin-10 (IL-10), interleukin-12 (IL-12), matrix metalloproteinase 2 (MMP2), IP-10, macrophage inflammatory protein 1α

(MIP1α

) and/or macrophage inflammatory protein 1β

(MIP1β

).

11. A method of treating a patient having AML or MDS, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 1.5 to about 12 mg/kg body weight,

whereby progression of the AML or MDS is inhibited,

wherein the humanized M195 antibody decreases the number of involved non-malignant effector cells, and/or decreases the levels of one or more inflammatory cytokines, chemokines or growth factors, in the patient, and

the method further comprises monitoring the number of involved non-malignant effector cells in the patient.

12. The method of claim 11, wherein the method further comprises monitoring the extent of cancer-associated cachexia responsive to the administration.

13. A method of treating a patient having AML or MDS, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 1.5 to about 12 mg/kg body weight,

whereby progression of the AML or MDS is inhibited,

wherein the patient is at least 60 years of age, and

wherein the patient has AML and the humanized M195 antibody is administered in combination with cytarabine.

14. A method of preventing or delaying recurrence of an acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), comprising:

administering to a patient in remission from the AML or MDS an unconjugated humanized M195 antibody at a dose of 1.5 to about 12 mg/kg,

whereby recurrence of the AML or MDS is delayed or prevented.

15. The method of claim 14, wherein the AML is resistant to chemotherapy.

16. The method of claim 14, wherein the humanized M195 antibody is administered in combination with at least one chemotherapeutic agent effective against cancer.

17. The method of claim 16, wherein the chemotherapeutic agent is Velcade®

(bortezomib), Revlimid®

(lenalidomide), Vidaza®

(azacytidine), Dacogen®

(Decitabine) or cytarabine.

18. The method of claim 14, wherein the patient is free of detectable cells of the AML or MDS.

19. The method of claim 14, wherein the patient in remission has undergone a bone marrow transplant.

20. The method of claim 19, wherein the bone marrow transplant is an autologous bone marrow transplant.

21. The method of claim 14, wherein the patient is at least 60 years of age.

22. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 550-650 mg regardless of body weight, wherein the humanized M195 antibody is administered in combination with at least one chemotherapeutic agent effective against cancer.

23. The method of claim 22, wherein the chemotherapeutic agent is Velcade®

(bortezomib), Revlimid®

(lenalidomide), Vidaza®

(azacytidine), Dacogen®

(Decitabine) or cytarabine.

24. The method of claim 23, wherein the chemotherapeutic agent is Revlimid®

(lenalidomide).

25. The method of claim 23, wherein the chemotherapeutic agent is Vidaza®

(azacytidine).

26. The method of claim 23, wherein the chemotherapeutic agent is cytarabine.

27. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 550-650 mg regardless of body weight, whereby at least one symptom of AML associated cachexia is reduced, and wherein the AML or MDS is CD33-negative.

28. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising:

(i) administering an unconjugated humanized M195 antibody to the patient at a dose of 550-650 mg regardless of body weight, and

(ii) monitoring in the patient;

(a) the levels of one or more inflammatory cytokines, chemokines or growth factors,

(b) the number of involved non-malignant effector cells, or

(c) the extent of cancer-associated cachexia responsive to the administration.

29. The method of claim 28, wherein the one or more inflammatory cytokines, chemokines or growth factors are interleukin-1β

(IL-1β

), tumor necrosis factor-α

(TNF-α

), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ

(IFN-γ

), vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-1 (MCP-1), RANTES, interleukin-10 (IL-10), interleukin-12 (IL-12), matrix metalloproteinase 2 (MMP2), IP-10, macrophage inflammatory protein 1α

(MIP1α

) and/or macrophage inflammatory protein 1β

(MIP1β

).

30. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 550-650 mg regardless of body weight, wherein the patient has AML and is at least 60 years of age, and the humanized M195 antibody is administered in combination with cytarabine.

31. A method of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 550-650 mg regardless of body weight, wherein the antibody is administered in order to prevent or delay recurrence of AML or MDS in the patient in remission, and the patient is free of detectable cells of the AML or MDS.

32. A method of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 550-650 mg regardless of body weight, wherein the antibody is administered in order to prevent or delay recurrence of AML or MDS in the patient in remission, and the patient has undergone a bone marrow transplant.

33. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of 600 mg regardless of body weight.

34. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of about 600 mg regardless of body weight in combination with cytarabine.

35. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of about 600 mg regardless of body weight, and wherein the AML or MDS is CD33-negative.

36. A method of treating AML or MDS in a patient, or of preventing or delaying recurrence of AML or MDS in a patient in remission, comprising:

(i) administering an unconjugated humanized M195 antibody to the patient at a dose of about 600 mg regardless of body weight, and

(ii) monitoring in the patient;

(a) the levels of one or more inflammatory cytokines, chemokines or growth factors,

(b) the number of involved non-malignant effector cells, or

(c) the extent of cancer-associated cachexia responsive to the administration.

37. A method of treating AML in a patient, or of preventing or delaying recurrence of AML in a patient in remission, comprising administering an unconjugated humanized M195 antibody to the patient at a dose of about 600 mg regardless of body weight in combination with cytarabine, wherein the patient is at least 60 years of age.

38. A method of preventing or delaying recurrence of AML or MDS, comprising administering an unconjugated humanized M195 antibody to a patient in remission from the AML or MDS at a dose of about 600 mg regardless of body weight, wherein the patient is free of detectable cells of the AML or MDS or has undergone a bone marrow transplant.