Cell-targeting molecules comprising protease-cleavage resistant, Shiga toxin A subunit effector polypeptides and carboxy-terminal moieties
US-10815469-B2 · Oct 27, 2020 · US
US12312411B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-12312411-B2 |
| Application number | US-202217810377-A |
| Country | US |
| Kind code | B2 |
| Filing date | Jul 1, 2022 |
| Priority date | Jan 23, 2019 |
| Publication date | May 27, 2025 |
| Grant date | May 27, 2025 |
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Provided in this disclosure are anti-CD38 binding domains, a composition comprising the anti-CD38 binding domains, nucleic acids encoding the anti-CD38 binding domains, and a method of using the anti-CD38 binding domains or the composition for treating multiple myeloma.
Opening claim text (preview).
The invention claimed is: 1. A composition comprising an anti-CD38-antigen binding domain that comprises a variable heavy domain (VH) comprising the sequence of SEQ ID NO: 9 and a variable light domain (VL) comprising the sequence of SEQ ID NO:13. 2. A composition comprising an anti-CD38-antigen binding domain that comprises a VH comprising the sequence of SEQ ID NO:17 and a VL comprising the sequence of SEQ ID NO:21. 3. A composition comprising an anti-CD38-antigen binding domain that comprises a VH comprising the sequence of SEQ ID NO: 53 and a VL comprising the sequence of SEQ ID NO: 57. 4. The composition according to claim 1 , wherein said VH and said VL are in a single polypeptide. 5. The composition according to claim 4 wherein, said polypeptide comprises a scFv linker and said polypeptide has the orientation from N- to C-terminal of VL-scFv linker-VH. 6. A composition according to claim 1 , wherein said composition is an antibody comprising: a) a heavy chain comprising said VH; and b) a light chain comprising said VL. 7. The composition according to claim 6 , wherein said heavy chain comprises said variable heavy domain and a heavy constant domain selected from the group consisting of the heavy constant domains of human IgG1, IgG2 and IgG4, or variants thereof. 8. The composition according to claim 7 , wherein said heavy constant domain is the heavy constant domain of human IgG1. 9. The composition according to claim 8 , wherein said heavy constant domain is a variant of the heavy constant domain of human IgG1. 10. The composition according to claim 9 , wherein said variant heavy constant domain of human IgG1 has ablated FcγR binding. 11. A nucleic acid composition encoding said composition according to claim 7 , wherein said nucleic acid composition comprises: a) a first nucleic acid encoding said first polypeptide; and b) a second nucleic acid encoding said second polypeptide. 12. A nucleic acid composition comprising a nucleic acid encoding said composition according to claim 4 . 13. An expression vector composition comprising said nucleic acid of claim 12 . 14. An expression vector composition comprising said first and second nucleic acids of claim 11 . 15. An expression vector composition comprising: a) a first expression vector comprising said first nucleic acid of claim 11 ; and b) a second expression vector comprising said second nucleic acid of claim 11 . 16. A host cell comprising said expression vector composition according to claim 13 . 17. A method of making a composition comprising an anti-CD38 antigen binding domain, comprising culturing said host cell of claim 16 under conditions wherein said composition comprising the anti-CD38 binding domain is expressed, and recovering said composition. 18. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of said composition according to claim 1 . 19. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of said composition according to claim 2 . 20. A method of treating multiple myeloma comprising administering to a subject in need thereof an effective amount of said composition according to claim 3 .
Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title
Complement-dependent cytotoxicity [CDC] · CPC title
Antibody-dependent cellular cytotoxicity [ADCC] · CPC title
Single chain antibody (scFv) · CPC title
Complementarity determining region [CDR] · CPC title
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