Ceacam5-dependent 4-1bb-agonistic bispecific antibodies
Patent Information
- Application Number
- HK62026125641
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-02-28
- Filing Date
- 2026-07-02
- Publication Date
- 2026-09-25
- Estimated Expiration
- 2044-02-27
Smart Images
Figure 00000031_0000 
Figure 00000032_0000 
Figure 00000033_0000
Abstract
Description
Abstract This invention provides bispecific or multispecific antibodies comprising an anti-CEACAM5 moiety and one or more anti-4-1BB nanoantibodies, the agonist activity of which depends on the presence of the CEACAM5 antigen. Such bispecific or multispecific antibodies are safe and effective for treating cancer and possess long-term protective immune memory against tumors. This invention also provides methods for treating diseases such as cancer using these antibodies.
Claims
1.A bispecific antibody, comprising one or more anti-4-1BB single domain antibodies (VHH) and an anti-CEACAM5 antibody or antigen-binding fragment thereof, wherein the one or more anti-4-1BB single domain antibodies each comprises a complementarity determining region 1 (VHH CDR1) , a VHH CDR2 and a VHH CDR3, wherein(a) the VHH CDR1 comprises the amino acid sequence of SEQ ID NO: 21; the VHH CDR2 comprises the amino acid sequence of SEQ ID NO: 22 or 24, and the VHH CDR3 comprises the amino acid sequence of SEQ ID NO: 23; or(b) the VHH CDR1 comprises the amino acid sequence of SEQ ID NO: 21 or 27; the VHH CDR2 comprises the amino acid sequence of SEQ ID NO: 25 or 28, and the VHH CDR3 comprises the amino acid sequence of SEQ ID NO: 26.2.The bispecific antibody of claim 1, wherein the VHH CDR1 comprises the amino acid sequence of SEQ ID NO: 21, the VHH CDR2 comprises the amino acid sequence of SEQ ID NO: 22, and the VHH CDR3 comprises the amino acid sequence of SEQ ID NO: 23.3.The bispecific antibody of claim 2, wherein the one or more anti-4-1BB single domain antibodies each comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 2-10 and 37-38.4.The bispecific antibody of claim 2, wherein the one or more anti-4-1BB single domain antibodies each comprises the amino acid sequence of SEQ ID NO: 37.5.The bispecific antibody of any preceding claim, further comprising an IgG Fc fragment.6.The bispecific antibody of claim 5, wherein the Fc fragment is N-terminal to two anti-4-1BB single domain antibodies, optionally through a peptide linker.7.The bispecific antibody of claim 5 or 6, wherein the Fc fragment is C-terminal to two anti-CEACAM5 fragments.8.The bispecific antibody of any preceding claim, which comprises a full-size IgG anti-CEACAM5 antibody and two anti-4-1BB single domain antibodies fused to the C-terminus of the anti-CEACAM5 antibody.9.The bispecific antibody of any preceding claim, wherein the anti-CEACAM5 antibody or antigen-binding fragment comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 31, a VH CDR2 includes the amino acid sequence of SEQ ID NO: 32, a VH CDR3 includes the amino acid sequence of SEQ ID NO: 33, a VL CDR1 includes the amino acid sequence of SEQ ID NO: 34, a VL CDR2 includes the amino acid sequence of SEQ ID NO: 35, and a VL CDR3 includes the amino acid sequence of SEQ ID NO: 36.10.The bispecific antibody of claim 9, wherein the anti-CEACAM5 antibody or antigen-binding fragment comprises a VH comprising the amino acid sequence of SEQ ID NO: 29 and a VL comprising the amino acid sequence of SEQ ID NO: 30.11.One or more polynucleotide (s) encoding the bispecific antibody of any one of claims 1-10.12.A cell comprising the polynucleotide of claim 11.13.A composition comprising the bispecific antibody of any one of claims 1-10 and a pharmaceutically acceptable carrier.14.A method of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of the bispecific antibody of any one of claims 1-10.15.The method of claim 14, wherein the cancer is characterized with expression of CEACAM5.