Compositions and methods for the treatment of platinum-drug resistant cancer
AssigneesZymeworks Inc., Var2 Pharmaceuticals Aps
InventorsJohn Babcook, James R. Rich, Mads Daugaard, Ali El-Salanti
Life of this patent
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Abstract
VAR2CSA-drug conjugates for targeting and inhibiting the growth of cancer cells that have developed resistance to a platinum drug and the use of the conjugates in the treatment of platinum drug-resistant cancers. VAR2CSA-drug conjugates (VDCs) comprise a VAR2CSA polypeptide that is capable of binding to oncofetal chondroitin sulfate (ofCS) and one or more toxins having anti-cancer activity conjugated to the VAR2CSA polypeptide, either directly or via a linker.
Claims50
A method of treating a platinum drug-resistant cancer in a subject comprising administering to the subject an effective amount of a VAR2CSA-drug conjugate (VDC), the VDC comprising:
- a) a VAR2CSA polypeptide that specifically binds to oncofetal chondroitin sulfate (ofCS), and
- b) one or more toxins having anti-cancer activity conjugated to the VAR2CSA polypeptide,
- wherein the VAR2CSA polypeptide is a functional fragment of an extracellular portion of a native VAR2CSA protein, and wherein the functional fragment is between about 550 amino acids and about 1100 amino acids in length and comprises a sequential amino acid sequence of ID1 and DBL2Xb domains of the native VAR2CSA protein.
A method of treating cancer in a subject who has received a prior treatment regimen comprising a platinum drug, the method comprising administering to the subject an effective amount of a VAR2CSA-drug conjugate (VDC), the VDC comprising:
- a) a VAR2CSA polypeptide that specifically binds to oncofetal chondroitin sulfate (ofCS), and
- b) one or more toxins having anti-cancer activity conjugated to the VAR2CSA polypeptide,
- wherein the VAR2CSA polypeptide is a functional fragment of an extracellular portion of a native VAR2CSA protein, and wherein the functional fragment is between about 550 amino acids and about 1100 amino acids in length and comprises a sequential amino acid sequence of ID1 and DBL2Xb domains of the native VAR2CSA protein.
A method of inhibiting growth of a platinum drug-resistant tumor in a subject comprising administering to the subject an effective amount of a VAR2CSA-drug conjugate (VDC), the VDC comprising:
- a) a VAR2CSA polypeptide that specifically binds to oncofetal chondroitin sulfate (ofCS), and
- b) one or more toxins having anti-cancer activity conjugated to the VAR2CSA polypeptide,
- wherein the VAR2CSA polypeptide is a functional fragment of an extracellular portion of a native VAR2CSA protein, and wherein the functional fragment is between about 550 amino acids and about 1100 amino acids in length and comprises a sequential amino acid sequence of ID1 and DBL2Xb domains of the native VAR2CSA protein.
A method of inhibiting the proliferation of platinum drug-resistant cancer cells comprising contacting the cells with an effective amount of a VAR2CSA-drug conjugate (VDC), the VDC comprising:
- a) a VAR2CSA polypeptide that specifically binds to oncofetal chondroitin sulfate (ofCS), and
- b) one or more toxins having anti-cancer activity conjugated to the VAR2CSA polypeptide,
- wherein the VAR2CSA polypeptide is a functional fragment of an extracellular portion of a native VAR2CSA protein, and wherein the functional fragment is between about 550 amino acids and about 1100 amino acids in length and comprises a sequential amino acid sequence of ID1 and DBL2Xb domains of the native VAR2CSA protein.
Dependencies are inferred from the claim text.