Combined spherical nucleic acid and checkpoint inhibitor for antitumor therapy
AssigneeExicure Operating Company
InventorsPinal Patel, Weston Daniel, Alice Bexon, Matthias Schroff
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Abstract
Aspects of the invention are directed to methods of treating cancer using a combination of spherical nucleic acids (SNAs) and a checkpoint inhibitor. The SNA molecule comprises a core oligonucleotide shell of CpG oligonucleotides positioned on the exterior of this core. The SNA is administered at a fixed dose of 2mg to a solid tumour or tumour lesion, and is administered within 24 hours of the checkpoint inhibitor administration. The SNA can also be administered at a dose of 700 mg-900 mg every 2 weeks. The SNA can also be a CpG linked via a spacer to the exterior surface of a liposome core of 40 nm or less diameter.
Claims136
A method for treating cancer comprising:
- administering to a subject a spherical nucleic acid (SNA) and a checkpoint inhibitor,
- wherein the SNA comprises a core having an oligonucleotide shell comprised of CpG oligonucleotides positioned on the exterior of the core, wherein the SNA is administered to the subject at a fixed dose of at least about 2 mg to one solid tumor or tumor lesion or divided among two or more solid tumors or tumor lesions in the subject,
- wherein the SNA is administered within 24 hours of administration of the checkpoint inhibitor, to treat the cancer in the subject.
A method for treating cancer comprising:
- administering to a subject a spherical nucleic acid (SNA) and a checkpoint inhibitor,
- wherein the SNA comprises a core having an oligonucleotide shell comprised of CpG oligonucleotides positioned on the exterior of the core, wherein the SNA is administered at a dose of between 2 mg and 32 mg once a week or every three weeks,
- wherein the checkpoint inhibitor is administered at a dose of between 180 and 370 mg every three weeks, or at a dose of between 700 mg and 900 mg every two weeks,
- wherein the SNA is administered within 24 hours of the administration of the checkpoint inhibitor, and
- wherein the SNA and the checkpoint inhibitor are administered through different routes of administration to treat the cancer in the subject.
A method for treating cancer comprising:
- administering a therapeutic dose of a checkpoint inhibitor and a therapeutic dose of a spherical nucleic acid (SNA) comprising a CpG oligonucleotide linked through a spacer to an exterior surface of a liposome core having a mean diameter of less than 40 nm, wherein the SNA is administered by intratumoral injection into one tumor lesion or into multiple lesions at a dose of between 2 mg and 32 mg and wherein the checkpoint inhibitor is administered by intravenous injection at a dose of between 180 and 800 mg.
A method for treating cancer comprising:
- administering to a subject a spherical nucleic acid (SNA) and a checkpoint inhibitor,
- wherein the SNA comprises a core having an oligonucleotide shell comprised of CpG oligonucleotides positioned on the exterior of the core, wherein the SNA is administered to the subject at a fixed dose of between about 16 mg to about 32 mg to one solid tumor or tumor lesion or at a fixed dose of between about 16 mg to about 32 mg divided among two or more solid tumors or tumor lesions in the subject, wherein the SNA is administered within 24 hours of administration of the checkpoint inhibitor, to treat the cancer in the subject, wherein the cancer is Merkel cell carcinoma or cutaneous squamous cell carcinoma.
A method for treating cancer comprising:
- administering to a subject a spherical nucleic acid (SNA) and a checkpoint inhibitor,
- wherein the SNA comprises a core having an oligonucleotide shell comprised of CpG oligonucleotides positioned on the exterior of the core, wherein the SNA is administered at a dose of between about 16 mg to about 32 mg once a week,
- wherein the checkpoint inhibitor is administered at a dose of between 180 mg and 370 mg every three weeks or at a dose of between 700 mg and 900 mg every two weeks,
- wherein the SNA is administered within 24 hours of the administration of the checkpoint inhibitor, and
- wherein the SNA and the checkpoint inhibitor are administered through different routes of administration to treat the cancer in the subject, wherein the cancer is Merkel cell carcinoma or cutaneous squamous cell carcinoma.
A method of treating cancer comprising:
- administering a therapeutic dose of a spherical nucleic acid (SNA) comprising a CpG oligonucleotide linked through a spacer to an exterior surface of a liposome core having a diameter of less than about 40 nm and a checkpoint inhibitor, wherein the SNA is administered by intratumoral injection into multiple lesions at a dose of between about 16 mg and about 32 mg and the checkpoint inhibitor is administered by intravenous injection at a dose of between 180 and 370 mg or between 700 mg and 900 mg, wherein the cancer is Merkel cell carcinoma or cutaneous squamous cell carcinoma.
Dependencies are inferred from the claim text.