Methods for treatment of cancer with an anti-tigit antagonist antibody
US-2024424092-A1 · Dec 26, 2024 · US
US12049500B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-12049500-B2 |
| Application number | US-202218263430-A |
| Country | US |
| Kind code | B2 |
| Filing date | Mar 31, 2022 |
| Priority date | Mar 31, 2021 |
| Publication date | Jul 30, 2024 |
| Grant date | Jul 30, 2024 |
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The present invention relates to antibodies having specificity to Nectin-4 and uses thereof.
Opening claim text (preview).
The invention claimed is: 1. A monoclonal antibody or antigen-binding fragment thereof which binds to Nectin-4 comprising (a) a variable heavy chain (VH) region comprising complementarity-determining regions (CDRs) CDR-H1, CDR-H2 and CDR-H3, wherein (i) the CDR-H1 comprises an amino acid sequence according to SEQ ID NO: 7, (ii) the CDR-H2 comprises an amino acid sequence according to SEQ ID NO: 8, (iii) the CDR-H3 comprises an amino acid sequence according to SEQ ID NO: 9, and (b) a variable light chain (VL) region comprising complementarity-determining regions (CDRs) CDR-L1, CDR-L2 and CDR-L3, wherein (i) the CDR-L1 comprises an amino acid sequence according to SEQ ID NO: 10, (ii) the CDR-L2 comprises an amino acid sequence according to SEQ ID NO: 11, (iii) the CDR-L3 comprises an amino acid sequence according to SEQ ID NO: 12. 2. The antibody or antigen-binding fragment of claim 1 comprising (a) a VH region comprising an amino acid sequence according to SEQ ID NO: 13 or an amino acid sequence having an identity thereof of at least 85%, at least 90%, at least 95% or at least 99%, and (b) a VL region, particularly a VL region comprising an amino acid sequence according to SEQ ID NO:14 or an amino sequence having an identity thereof of at least 85%, at least 90%, at least 95% or at least 99%. 3. The antibody or antigen-binding fragment of claim 1 , which is a chimeric antibody, a multispecific antibody, a bispecific antibody, a human antibody, a humanized antibody or an antigen-binding fragment thereof. 4. The antibody or antigen-binding fragment of claim 1 , which is an antibody of class IgG, of class IgM, of class IgA or an antigen-binding fragment thereof, or which is a single-chain antibody, or an antibody Fv fragment. 5. A human or humanized monoclonal antibody or antigen-binding fragment thereof which binds to Nectin-4 comprising (a) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 27, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 28, or (b) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 41, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 42, or (c) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 55, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 56, or (d) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 69, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 70 or 103, or (e) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 41, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 56, or (f) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 41, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 70 or 103, or (g) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 55, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 70 or 103, or (h) (i) a VH region comprising an amino acid sequence according to SEQ ID NO: 69, and (ii) a VL region comprising an amino acid sequence according to SEQ ID NO: 56. 6. The antibody or fragment of claim 1 in combination with a carrier or excipient suitable for use in medicine. 7. The antibody or fragment of claim 1 in combination with a carrier suitable for administration to a subject suffering from or likely to suffer from cancer associated with Nectin-4 overexpression. 8. A nucleic acid coding for one or more antibodies according to claim 1 , or for at least one VL and/or one VH of said antibodies. 9. A vector comprising the nucleic acid according to claim 8 . 10. A host cell comprising the vector of claim 9 . 11. A pharmaceutical composition comprising an antibody or antigen-binding fragment thereof according to claim 1 . 12. The antibody or antigen-binding fragment of claim 4 , wherein said antibody of class IgG, has a subclass selected from the group consisting of IgG1, IgG2, IgG3 and IgG4. 13. The antibody or fragment of claim 6 , wherein said carrier or excipient is suitable for therapeutic or diagnostic applications. 14. The antibody or fragment of claim 13 , wherein said diagnostic applications include in vitro and in vivo diagnostic applications. 15. The antibody or antigen-binding fragment of claim 1 , wherein said antibody is a chimeric antibody or an antigen-binding fragment thereof. 16. The antibody or antigen-binding fragment of claim 1 , wherein said antibody is a humanized antibody or an antigen-binding fragment thereof. 17. The antibody or antigen-binding fragment of claim 1 , wherein said antibody is an antibody of subclass IgG1 or an antigen-binding fragment thereof. 18. The antibody or antigen-binding fragment of claim 1 , wherein said antibody is an antibody of subclass IgG2 or an antigen-binding fragment thereof. 19. The antibody or antigen-binding fragment of claim 1 , wherein said antibody is an antibody of subclass IgG3 or an antigen-binding fragment thereof. 20. The antibody or antigen-binding fragment of claim 1 , wherein said antibody is an antibody of subclass IgG4 or an antigen-binding fragment thereof.
Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title
Internalization into the cell · CPC title
Decreased effector function due to an Fc-modification · CPC title
Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title
comprising antibodies · CPC title
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