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Publication Number
US-12194056-B2
Publication Date
2025-01-14
Expiration Date
Abstract
Disclosed herein are CCR7 aptamers that specifically bind to and internalize into CCR7-expressing cells. The aptamers can be used as a therapeutic agent by itself or in combination with a small molecule by forming a conjugate with the small molecule. Targeted delivery of the small molecule can be achieved by such conjugates. Also disclosed are methods of treating a subject suffering from cancer by administering an effective amount of the aptamer or the aptamer-small molecule conjugate to the subject.
Core Innovation
The invention relates to high-affinity CCR7-targeting RNA aptamers, specifically C-1A (SEQ ID NO: 1), C-2A (SEQ ID NO: 2), DD9-9 (SEQ ID NO: 3), and C-6 (SEQ ID NO: 4), and to cell-type specific aptamer-small molecule conjugates. The conjugates include an aptamer that specifically binds CCR7 and a small molecule that is not an aptamer, and are configured to target CCR7-expressing cells and enable subsequent intracellular activity associated with the conjugated small molecule.
The invention provides chemically modified CCR7 aptamers selected from in-SELEX or post-SELEX chemical modification schemes and specifies aptamer chemical substitutions and end capping. The aptamers include modifications at the 2' position with fluoro (F), amino (NH2), or O-methyl (OCH3) groups, together with 3' inverted thymidine capping, in the context of maintaining CCR7 binding and cellular uptake.
The invention further provides aptamer-small molecule attachment formats and therapeutic compositions for cancer treatment. Conjugation is described as being accomplished via linkers and/or sticky bridges with complementary sequences, and the therapeutic composition can include a CCR7 aptamer alone or a conjugate of a CCR7 aptamer and a non-aptamer small molecule, including saRNA, siRNA, shRNA, miRNA, chemotherapeutic agents, and toxins.
The document also describes cancer therapeutics as including bi-specific and multi-specific aptamer constructs, including a MATE construct involving CD8, PD-1, and CCR7, and provides experimental examples showing CCR7 aptamer binding/internalization and functional gene silencing/activation and inhibition of CCR7-expressing tumor cell proliferation.
Claims Coverage
The independent claims cover two aspects of the invention: a cell-type specific CCR7 aptamer-small molecule conjugate with a defined aptamer set and attachment to a non-aptamer small-molecule payload, and a method of treating a cancer patient using the CCR7 aptamer or its conjugate with a non-aptamer small molecule. Overall, the claim framework centers on CCR7-specific aptamers selected from four sequences and therapeutic use with non-aptamer small molecules.
Ccr7-binding aptamer-small molecule conjugate with defined aptamer set
an aptamer that specifically binds CCR7, the aptamer selected from the group consisting of C-1A (SEQ ID NO: 1), C-2A (SEQ ID NO: 2), DD9-9 (SEQ ID NO: 3), and C-6 (SEQ ID NO: 4), and a small molecule conjugated to the aptamer, wherein the small molecule is not an aptamer.
Administering Ccr7 aptamer or Ccr7 aptamer conjugate for cancer treatment
a therapeutic composition comprises a CCR7 aptamer or a conjugate of a CCR7 aptamer and a small molecule, wherein the small molecule is not an aptamer, wherein the CCR7 aptamer is selected from the group consisting of C-1A (SEQ ID NO: 1), C-2A (SEQ ID NO: 2), DD9-9 (SEQ ID NO: 3), and C-6 (SEQ ID NO: 4).
Across the independent claims, the core coverage is directed to CCR7-targeting aptamers selected from C-1A, C-2A, DD9-9, and C-6, used either as CCR7 aptamers within a therapeutic composition or conjugated to a non-aptamer small molecule, for administration in a method of treating a cancer patient.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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