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US 12,343,401 B2Granted
Modular self assembly disassembly (SADA) technologies
AssigneeMemorial Sloan Kettering Cancer Center
InventorsBrian H. Santich, Mahiuddin Ahmed, Nai-Kong V. Cheung
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Abstract
The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.
Claims11
A method of treating or diagnosing cancer in a subject, comprising:
- a. providing a composition comprising a conjugate comprising a self-assembly disassembly (SADA) polypeptide having an amino acid sequence that is identical to a human homo-multimerizing polypeptide sequence comprising any one of SEQ ID NOs:
- 1, 3, 5, 7, 9, 11, 13, and 15 and having one or more multimerization dissociation constants (KD);
- and a bispecific antibody comprising a first scFv that binds a tumor target and a second scFv that binds a DOTA moiety comprising a radioactive payload, wherein (a) the first scFv is operably linked to the second scFv, (b) the second scFv includes a VH-CDR1 sequence comprising DYGVH (SEQ ID NO:
- 103), a VH-CDR2 sequence comprising VIWSGGGTAYNTALIS (SEQ ID NO:
- 104), a VH-CDR3 sequence comprising RGSYPYNYFDA (SEQ ID NO:
- 105), a VL-CDR1 sequence comprising GSSTGAVTASNYAN (SEQ ID NO:
- 106), a VL-CDR2 sequence comprising GHNNRPP (SEQ ID NO:
- 107), and a VH-CDR3 sequence comprising ALWYSDHWV (SEQ ID NO:
- 108);
- and (c) the second scFv is operably linked to the SADA polypeptide;
- b. administering the composition to a subject that is suffering from or susceptible to cancer;
- and
- c. administering a DOTA chelator comprising a radionuclide.
10 more elements
Dependencies are inferred from the claim text.