Compositions and methods for treatment of hematological malignancies

• US 10,000,549 B2
• Filed: 06/09/2016
• Issued: 06/19/2018
• Est. Priority Date: 09/28/2010
• Status: Active Grant

• Current Assignee: Hadasit Medical Research Services & Development Ltd (Hadassah, The Women's Zionist Organization of America, Inc.), KAHR Medical (2005) Ltd.
• Original Assignee: Hadasit Medical Research Services & Development Ltd (Hadassah, The Women's Zionist Organization of America, Inc.), KAHR Medical (2005) Ltd.
• Inventors: Dranitzki Elhalel, Michal
• Primary Examiner(s): Carlson, Karen Cochrane
• Application Number:
  US15/178,085
• Publication Number:
  US 20160340409A1
• Time in Patent Office: 740 Days
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07K 14/70521 CD28, CD152
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 14/70578 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 NGF-receptor C07K14/71, TNF-receptor C07K14/7151
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/21 containing a His-tag
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies

Abstract

Use of a chimeric protein selected from the group consisting of CTLA4-FasL and CD40-FasL proteins for treatment of lymphoma and/or a multiple myeloma and/or a leukemia as described herein, and pharmaceutical compositions and methods of treatment thereof.

Claims

1. A method of treating multiple myeloma, benign plasma cell disorder or premalignant forms of multiple myeloma in a subject, comprising administering to the subject a CD40-FasL chimeric protein, wherein cells of said multiple myeloma, said benign plasma cell disorder or said premalignant forms of multiple myeloma express CD40L.

2. The method of claim 1, wherein said multiple myeloma is selected from the group consisting of multiple myeloma cancers which produce light chains of kappa-type and/or light chains of lambda-type;

aggressive multiple myeloma;

smoldering multiple myeloma (SMM), indolent multiple myeloma, and primary amyloidosis.

3. The method of claim 2, wherein said aggressive multiple myeloma is primary plasma cell leukemia (PCL).

4. The method of claim 1, wherein said benign plasma cell disorder is selected from the group consisting of MGUS (monoclonal gammopathy of undetermined significance) and/or Waldenstrom'"'"'s macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) which may proceed to multiple myeloma.

5. The method of claim 4, to halt the progression of the benign plasma cell disorder to a malignant form of multiple myeloma.

6. The method of claim 1, wherein said chimeric protein is administered as a pharmaceutical composition comprising said chimeric protein and a

pharmaceutical carrier, adapted for treatment of said multiple myeloma, said benign plasma cell disorder or said premalignant forms of multiple myeloma.

7. The method of claim 6, wherein said multiple myeloma is selected from the group consisting of multiple myeloma cancers which produce light chains of kappa-type and/or light chains of lambda-type;

aggressive multiple myeloma;

smoldering multiple myeloma (SMM), indolent multiple myeloma, and primary amyloidosis.

8. The method of claim 7, wherein said multiple myeloma is primary plasma cell leukemia (PCL).

9. The method of claim 6, wherein said benign plasma cell disorder is selected from the group consisting of MGUS (monoclonal gammopathy of undetermined significance) and/or Waldenstrom'"'"'s macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) which may proceed to multiple myeloma.

10. The method of claim 9, to halt the progression of the benign plasma cell disorder to a malignant form of multiple myeloma.

11. A method of treating multiple myeloma, benign plasma cell disorder or premalignant forms of multiple myeloma in a subject, comprising administering to the subject a CTLA4-FasL chimeric protein.

12. The method of claim 11, wherein cells of said multiple myeloma, said benign plasma cell disorder or said premalignant forms of multiple myeloma express B7.

13. The method of claim 11, wherein said multiple myeloma is selected from the group consisting of multiple myeloma cancers which produce light chains of kappa-type and/or light chains of lambda-type;

aggressive multiple myeloma;

smoldering multiple myeloma (SMM), indolent multiple myeloma, and primary amyloidosis.

14. The method of claim 13, wherein said aggressive multiple myeloma is primary plasma cell leukemia (PCL).

15. The method of claim 11, wherein said benign plasma cell disorder is selected from the group consisting of MGUS (monoclonal gammopathy of undetermined significance) and/or Waldenstrom'"'"'s macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) which may proceed to multiple myeloma.

16. The method of claim 15, to halt the progression of the benign plasma cell disorder to a malignant form of multiple myeloma.

17. The method of claim 11, wherein said chimeric protein is administered as a pharmaceutical composition comprising said chimeric protein and a pharmaceutical carrier, adapted for treatment of said multiple myeloma, said benign plasma cell disorder or said premalignant forms of multiple myeloma.

18. The method of claim 17, wherein cells of said multiple myeloma, said benign plasma cell disorder or said premalignant forms of multiple myeloma express B7.

19. The method of claim 17, wherein said multiple myeloma is selected from the group consisting of multiple myeloma cancers which produce light chains of kappa-type and/or light chains of lambda-type;

aggressive multiple myeloma;

smoldering multiple myeloma (SMM), indolent multiple myeloma, and primary amyloidosis.

20. The method of claim 19, wherein said multiple myeloma is primary plasma cell leukemia (PCL).

21. The method of claim 11, wherein said benign plasma cell disorder is selected from the group consisting of MGUS (monoclonal gammopathy of undetermined significance) and/or Waldenstrom'"'"'s macroglobulinemia (WM, also known as lymphoplasmacytic lymphoma) which may proceed to multiple myeloma.

22. The method of claim 21, to halt the progression of the benign plasma cell disorder to a malignant form of multiple myeloma.