Liposomes coated with selected antibodies that bind to aminophospholipids
AssigneeBoard of Regents, The University of Texas
InventorsPhilip E. Thorpe, Xianming Huang, Sophia Ran
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Abstract
Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.
Claims63
A liposome comprising an antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
- (a) a heavy chain variable region that comprises variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VH CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12;
- and
- (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VL CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15.
A composition comprising a stealthed liposome operatively associated with a first and second therapeutic agent, wherein said first therapeutic agent is an antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
- (a) a heavy chain variable region that comprises variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VH CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12;
- and
- (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VL CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15.
A liposomal formulation comprising a stealthed liposome coated with a first therapeutic agent, wherein said first therapeutic agent is an antibody, or antigen- binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
- (a) a heavy chain variable region that comprises variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VH CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12;
- and
- (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said VL CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15.
A liposomal formulation comprising a stealthed liposome coated with an antibody, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
- (a) a heavy chain variable region that comprises a variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable heavy (VH) CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12;
- and
- (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable light (VL) CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15.
A liposome comprising a first therapeutic agent, wherein said first therapeutic agent is an antibody, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
- (a) a heavy chain variable region that comprises a variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable heavy (VH) CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12;
- and
- (b) a light chain variable region that comprises a variable light (VL) CDR1 , VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable light (VL) CDR1 that has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15.
A liposome comprising monoclonal antibody 3G4produced by hybridoma ATCC PTA 4545, or an antigen-binding fragment thereof.
A composition comprising a stealthed liposome operatively associated with a first and second therapeutic agent, wherein said first therapeutic agent is an antibody, that comprises at least two variable regions that each comprises three CDRs, wherein said two variable regions are:
- (a) a heavy chain variable region that comprises a variable heavy (VH) CDR1, VH CDR2 and VH CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable heavy (VH) CDR1 has the amino acid sequence of SEQ ID NO:10, said VH CDR2 has the amino acid sequence of SEQ ID NO:11 and said VH CDR3 has the amino acid sequence of SEQ ID NO:12;
- and
- (b) a light chain variable region that comprises a variable light (VL) CDR1, VL CDR2 and VL CDR3 from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, wherein said variable light (VL) CDR1 has the amino acid sequence of SEQ ID NO:13, said VL CDR2 has the amino acid sequence of SEQ ID NO:14 and said VL CDR3 has the amino acid sequence of SEQ ID NO:15.
A composition comprising a stealthed liposome operatively associated with a first and second therapeutic agent, wherein said first therapeutic agent is monoclonal antibody 3G4produced by hybridoma ATCC PTA 4545, or an antigen-binding fragment thereof.
A liposomal formulation comprising a stealthed liposome coated with monoclonal antibody 3G4produced by hybridoma ATCC PTA 4545, or an antigen-binding fragment thereof.
A liposome comprising an antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein at least one of said variable regions is:
- (a) a heavy chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:2;
- or
- (b) a light chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:4.
A composition comprising a stealthed liposome operatively associated with a first and second therapeutic agent, wherein said first therapeutic agent is an antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein at least one of said variable regions is:
- (a) a heavy chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:2;
- or
- (b) a light chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:4.
A liposomal formulation comprising a stealthed liposome coated with a first therapeutic agent, wherein said first therapeutic agent is an antibody, or antigen-binding fragment thereof, that comprises at least two variable regions that each comprises three CDRs, wherein at least one of said variable regions is:
- (a) a heavy chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:2;
- or
- (b) a light chain variable region from the monoclonal antibody 3G4, produced by hybridoma ATCC PTA 4545, which has the amino acid sequence of SEQ ID NO:4.
A liposome comprising monoclonal antibody 3G4produced by hybridoma ATCC PTA 4545.
Dependencies are inferred from the claim text.