Hematologic cancer treatments

Patent metadata

Field	Value
Publication number	US-2017232102-A1
Application number	US-201715430411-A
Country	US
Kind code	A1
Filing date	Feb 10, 2017
Priority date	Feb 12, 2016
Publication date	Aug 17, 2017
Grant date	—

Abstract

Disclosed herein are improved compositions and methods involved in treating hematologic cancers, i.e., cancers that begin in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. The compositions comprise complexes containing albumin-containing nanoparticles (e.g., ABRAXANE® nanoparticles) and antibodies. The compositions are used to effect hematologic cancer cell death.

First claim

What is claimed is:

1 . A unit dose of a composition comprising albumin-containing nanoparticles complexed with an antibody wherein said nanoparticles contain albumin and paclitaxel at a ratio of about 9:1 albumin to paclitaxel as well as a plurality of humanized antibodies complexed thereto wherein said nanoparticles are solids which have a size less than 1 micron provided that at least a portion of the said antibodies are arranged in a manner that said nanoparticle complexes retain antibody mediated target binding specificity and wherein the antibody is an anti-CD52 polypeptide humanized antibody-or an anti-CD38 polypeptide humanized antibody, wherein said unit dose comprises from about 17.5 mg/m 2 to about 125 mg/m 2 of said antibody and about 75 mg/m 2 to about 250 mg/m 2 paclitaxel.

2 . The nanoparticles of claim 1 wherein the antibody is rituximab, Alemtuzumab, or SAR650984.

3 . The nanoparticle of claim 2 wherein the antibody is rituximab.

4 . The nanoparticles of claim 1 wherein the antibodies are non-covalently complexed with the nanoparticles.

5 . A method to effect hematological cancer cell death said method comprising contacting the cancer cell with a composition comprising albumin-containing nanoparticles complexed with an antibody wherein said nanoparticles contain albumin and paclitaxel at a ratio of about 9:1 albumin to paclitaxel as well as a plurality of humanized antibodies complexed thereto wherein said nanoparticles are solids which have a size less than 1 micron provided that at least a portion of the said antibodies are arranged in a manner that said nanoparticle-complexes retain antibody mediated target binding specificity and wherein the antibody is an anti-CD52 polypeptide humanized antibody or an anti-CD38 polypeptide humanized antibody, wherein said unit dose comprises from about 17.5 mg/m 2 to about 125 mg/m 2 of said antibody and about 75 mg/m 2 to about 250 mg/m 2 paclitaxel.

6 . The method of claim 5 , wherein the hematologic cancer cell is a leukemia cell, a lymphoma cell, or myeloma cell.

7 . The method of claim 6 , wherein the leukemia cell is an acute myelogenous (granulocytic) leukemia (AML) cell, chronic myelogenous (granulocytic) leukemia (CML) cell, acute lymphocytic (lymphoblastic) leukemia (ALL) cell, chronic lymphocytic leukemia (CLL) cell, or hairy cell leukemia).

8 . The method of claim 6 , wherein the lymphomas cell is a cell of a mature B-cell neoplasm, a mature T cell neoplasm, a mature natural killer cell neoplasm, an immunodeficiency-associated lymphoproliferative disorders, Hodgkin lymphoma cell, and non-Hodgkin lymphoma cell.

9 . The method of claim 6 , wherein the myeloma is a multiple myeloma cell.

10 . The method of claim 5 , wherein the unit dose comprises about 100 mg/m 2 to about 200 mg/m 2 paclitaxel.

11 . The method of claim 5 , wherein the unit dose comprises about 150 mg/m 2 paclitaxel.

12 . The method of claim 5 , wherein the unit dose comprises about 35 mg/m 2 to about 100 mg/m 2 of the antibody.

13 . The method of claim 5 , wherein the unit dose comprises about 50 to about 100 mg/m 2 of the antibody.

14 . A method for lysing a hematological cancer cell in a patient, the method comprises administering to the patient an effective amount of a composition comprising albumin-containing nanoparticles complexed with an antibody wherein said nanoparticles contain albumin and paclitaxel at a ratio of about 9:1 albumin to paclitaxel as well as a plurality of humanized antibodies complexed thereto wherein said nanoparticles are solids which have a size less than 1 micron provided that at least a portion of the said antibodies are arranged in a manner that said nanoparticle-complexes retain antibody mediated target binding specificity and wherein the antibody is an anti-CD52 polypeptide humanized antibody or an-anti-CD38 polypeptide humanized antibody, wherein said unit dose comprises from about 17.5 mg/m 2 to about 125 mg/m 2 of said antibody and about 75 mg/m 2 to about 250 mg/m 2 paclitaxel.

15 . The method of claim 14 , wherein the unit dose comprise about of 100 mg/m 2 to about 200 mg/m 2 paclitaxel.

16 . The method of claim 14 , wherein the unit dose comprise about 150 mg/m 2 paclitaxel.

17 . The method of claim 14 , wherein the unit dose comprise about 35 mg/m 2 to about 100 mg/m 2 antibody.

18 . The method of claim 14 , wherein the unit dose comprise about 50 to about 100 mg/m 2 .

19 . The method of claim 14 , wherein the hematologic cancer cell is a leukemia cell, a lymphoma cell, or myeloma cell.

20 . The method of claim 19 , wherein the leukemia cell is an acute myelogenous (granulocytic) leukemia (AML) cell, chronic myelogenous (granulocytic) leukemia (CML) cell, acute lymphocytic (lymphoblastic) leukemia (ALL) cell, chronic lymphocytic leukemia (CLL) cell, or hairy cell leukemia).

21 . The method of claim 19 , wherein the lymphomas cell is a cell of a mature B-cell neoplasm, a mature T cell neoplasm, a mature natural killer cell neoplasm, an immunodeficiency-associated lymphoproliferative disorders, Hodgkin lymphoma, and non-Hodgkin lymphoma.

22 . The method of claim 18 , wherein the myeloma is a multiple myeloma cell.

23 . The method of claim 14 , wherein the patient is a mammal.

24 . The method of claim 23 , wherein the mammal is a human.

25 . The method of claim 14 , wherein said pharmaceutical composition comprises a humanized anti-CD52 polypeptide antibody.

26 . The method of claim 14 , wherein said pharmaceutical composition comprises a humanized anti-CD38 polypeptide antibody.

27 . A unit dose of a composition comprising albumin-containing nanoparticles complexed with an antibody wherein said nanoparticles contain albumin and paclitaxel at a ratio of about 9:1 albumin to paclitaxel as well as a plurality of humanized antibodies complexed thereto wherein said nanoparticles are solids which have a size less than 1 micron provided that at least a portion of the said antibodies are arranged in a manner that said nanoparticle complexes retain antibody mediated target binding specificity and wherein the antibody is an anti-CD20 polypeptide humanized antibody, wherein said unit dose comprises from about 17.5 mg/m 2 to about 125 mg/m 2 of said antibody and about 75 mg/m 2 to about 250 mg/m 2 paclitaxel.

Assignees

• Mayo Foundation

Inventors

• Markovic Svetomir N
• Nevala Wendy K

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K47/68

  the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• C07K16/3061

  Blood cells · CPC title

• C07K16/2887

  against CD20 · CPC title