Sheddase inhibitors combined with CD30-binding immunotherapeutics for the treatment of CD30 positive diseases

• US 7,910,108 B2
• Filed: 06/04/2007
• Issued: 03/22/2011
• Est. Priority Date: 06/05/2006
• Status: Active Grant

• Current Assignee: Incyte Corporation, Incyte Holdings Corporation (Incyte Corporation)
• Original Assignee: Incyte Corporation
• Inventors: Friedman, Steven M., Scherle, Peggy A., Vaddi, Krishna, Newton, Robert C.
• Primary Examiner(s): HUFF, SHEELA JITENDRA
• Application Number:
  US11/757,600
• Publication Number:
  US 20070280943A1
• Time in Patent Office: 1,387 Days
• Field of Search: None
• US Class Current: 424/155.1
• 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 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95

Abstract

The present invention is directed to pharmaceutical methods for the treatment of CD30 positive diseases, such as Hodgkin'"'"'s disease, by administration of a combination of at least one sheddase inhibitor and at least one anti-CD30 immunotherapeutic.

Claims

1. A method of treating a disease characterized by expression of CD30 or CD30 shedding selected from lymphoma, T-cell leukemia, and adult T-cell leukemia (ATL) in a human patient, comprising administering to said human patient:

i) an antibody or antibody-conjugate which binds CD30; and

ii) methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate, or a pharmaceutically acceptable salt thereof;

wherein the amount of said methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate, or said pharmaceutically acceptable salt thereof, and said antibody or antibody-conjugate together provide a therapeutically effective amount.

2. The method of claim 1 wherein said lymphoma is Hodgkin'"'"'s disease (HD), Burkitt'"'"'s lymphoma, anaplastic large-cell lymphoma (ALCL), cutaneous T-cell lymphoma, nodular small cleaved-cell lymphoma, lymphocytic lymphoma, peripheral T-cell lymphomas, Lennert'"'"'s lymphoma, immunoblastic lymphoma, or entroblastic/centrocytic follicular lymphoma.

3. The method of claim 1 wherein said disease is T cell leukemia or adult T-cell leukemia (ATL).

4. The method of claim 1 wherein an antibody which binds CD30 is administered.

5. The method of claim 4 wherein said antibody is a monoclonal antibody.

6. The method of claim 4 wherein said antibody is a human, humanized, or chimeric antibody.

7. The method of claim 1 wherein an antibody-conjugate which binds CD30 is administered.

8. The method of claim 7 wherein said antibody-conjugate is an anti-CD30 antibody conjugated with a cytotoxin or radiotoxin.

9. The method of claim 8 wherein said antibody-conjugate is a monoclonal anti-CD30 antibody conjugated with a cytotoxin or radiotoxin.

10. The method of claim 9 wherein said antibody-conjugate is a human, humanized, or chimeric anti-CD30 antibody conjugated with a cytotoxin or radiotoxin.

11. The method of claim 1 wherein said administering is carried out such that the physiological effects of both said methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate, or said pharmaceutically acceptable salt thereof, and said antibody or antibody conjugate overlap in said patient.

12. The method of claim 1, wherein said disease is lymphoma.