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US 8,709,430 B2Granted
Cancer treatment kits comprising therapeutic antibody conjugates that bind to aminophospholipids
AssigneeBoard of Regents, The University of Texas System
InventorsPhilip E. Thorpe, Sophia Ran, Rolf A. Brekken
Life of this patent
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Abstract
Disclosed is the surprising discovery that aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.
Claims32
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first monoclonal antibody, or antigen-binding fragment thereof, that binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct.
In combination, biologically effective amounts of:
- (a) a first composition comprising at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first monoclonal antibody, or antigen-binding fragment thereof, that binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- (b) a second composition comprising an antibody-detectable agent construct that comprises a detectable agent operatively attached to a second monoclonal antibody, or antigen-binding fragment thereof, that binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (c) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct.
1 more element
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first monoclonal antibody, or antigen-binding fragment thereof, operatively attached to at least a first therapeutic agent, wherein said at least a first monoclonal antibody, or antigen-binding fragment thereof, binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct;
- wherein said at least a second anti-cancer agent:
- (i) increases aminophospholipid expression in the endothelium of said blood vessels of said vascularized tumor or injures or induces apoptosis in the endothelium of said blood vessels of said vascularized tumor;
- or
- (ii) kills tumor cells of said tumor or is an anti-angiogenic agent that inhibits metastasis of tumor cells.
4 more elements
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first monoclonal antibody that binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct.
In combination, biologically effective amounts of:
- (a) a first composition comprising at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first monoclonal antibody that binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- (b) a second composition comprising an antibody-detectable agent construct that comprises a detectable agent operatively attached to a second monoclonal antibody, or antigen-binding fragment thereof, that binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (c) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct.
1 more element
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first monoclonal antibody operatively attached to at least a first therapeutic agent, wherein said at least a first monoclonal antibody binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct;
- wherein said at least a second anti-cancer agent:
- (i) increases aminophospholipid expression in the endothelium of said blood vessels of said vascularized tumor or injures or induces apoptosis in the endothelium of said blood vessels of said vascularized tumor;
- or
- (ii) kills tumor cells of said tumor or is an anti-angiogenic agent that inhibits metastasis of tumor cells.
4 more elements
A kit comprising, in a pharmaceutically acceptable form, therapeutically effective amounts of:
- (a) at least a first anti-cancer agent, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first monoclonal antibody, or antigen-binding fragment thereof, that binds to a phosphatidylethanolamine-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct.
A kit comprising, in a pharmaceutically acceptable form:
- (a) an amount of at least a first anti-cancer agent effective to kill at least a portion of the endothelial cells of tumor blood vessels, promote coagulation in at least a portion of tumor blood vessels, or destroy or occlude at least a portion of tumor blood vessels upon administration to an animal having a vascularized tumor, wherein said at least a first anti-cancer agent is at least a first antibody-therapeutic agent construct that comprises at least a first therapeutic agent operatively attached to at least a first monoclonal antibody, or antigen-binding fragment thereof, that targets and binds to an aminophospholipid-protein complex on the luminal surface of blood vessels of a vascularized tumor;
- and
- (b) at least a second anti-cancer agent other than said at least a first antibody-therapeutic agent construct.
Dependencies are inferred from the claim text.