Vhh-based nkp46 binders

Abstract

The present disclosure relates to VHH-based NKp46 binders with favorable characteristics. Moreover, the present disclosure relates to pharmaceutical compositions comprising such a compound and the use of such compounds and such pharmaceutical compositions in medical treatment methods.

Description

Abstract This disclosure relates to VHH-based NKp46 binders having advantageous properties. Furthermore, this disclosure relates to pharmaceutical compositions comprising such compounds, and the use of such compounds and such pharmaceutical compositions in medical treatments.

Claims

CLAIMSA compound comprising a VHH antibody domain or a fragment thereof, wherein(a) said VHH antibody domain or fragment thereof comprises the complementarity determining regions CDR1, CDR2 and CDR3 of one VHH selected from the group consisting of VHH NKp46.1, VHH NKp46.2, VHH NKp46.3, VHH NKp46.4, VHH NKp46.5, VHH NKp46.6, VHH NKp46.7, VHH NKp46.8,VHH NKp46.9, VHH NKp46.10, VHH NKp46.11, VHH NKp46.12, VHHNKp46.13, VHH NKp46.14, VHH NKp46.15, VHH NKp46.16, VHHNKp46.17, VHH NKp46.18, VHH NKp46.20, VHH NKp46.21, VHHNKp46.22, VHH NKp46.23, VHH NKp46.24, VHH NKp46.25, VHHNKp46.26, VHH NKp46.27, VHH NKp46.28, VHH NKp46.29, VHHNKp46.31 and VHH NKp46.34 as shown in the Table of CDRs below;(b) said VHH antibody domain or fragment thereof comprises the complementarity determining regions CDR1, CDR2 and CDR3 as defined in (a) with modification, wherein the modification is that the sequence of at least one of CDR1, CDR2 and CDR3 is humanized; or(c) said VHH antibody domain or fragment thereof comprises the complementarity determining regions CDR1, CDR2 and CDR3 as defined in (a) with modification, wherein the modification is the replacement, addition or deletion of up to three amino acids in CDR1, the replacement, addition or deletion of up to three amino acids in CDR2 and / or the replacement, addition or deletion of up to three amino acids in CDR3;Table of CDRs:1631642. A compound comprising a VHH antibody domain or a fragment thereof, wherein(A) said VHH antibody domain comprises the VHH sequence of a VHH selected from the group consisting of VHH NKp46.1, VHH NKp46.2, VHH NKp46.3, VHH NKp46.4, VHH NKp46.5, VHH NKp46.6, VHH NKp46.7, VHH NKp46.8, VHH NKp46.9, VHH NKp46.10, VHH NKp46.11, VHH NKp46.12, VHH NKp46.13, VHH NKp46.14, VHH NKp46.15, VHH NKp46.16, VHH NKp46.17, VHH NKp46.18, VHH NKp46.20, VHH NKp46.21, VHHNKp46.22, VHH NKp46.23, VHH NKp46.24, VHH NKp46.25, VHHNKp46.26, VHH NKp46.27, VHH NKp46.28, VHH NKp46.29, VHHNKp46.31 and VHH NKp46.34 as shown in the Table of VHH Sequences below;165(B) said VHH antibody domain comprises a VHH sequence as defined in (A) with modification, wherein the modification is that said sequence is humanized;(C) said VHH antibody domain comprises a VHH sequence as defined in (A) with modification, wherein the modification is the replacement, addition or deletion of up to 25 amino acids; or(D) said VHH antibody domain comprises a VHH sequence that is at least 75% identical to a VHH sequence referred to in (A);Table of VHH Sequences:1663. The compound according to any one of claims 1 or 2, wherein said compound binds to NKp46 with a KD of l >< 10'6M or stronger in a binding assay by BLI (biolayer interferometry) with recombinant extracellular domain of NKp46 (NKp46-ECD, SEQ ID NO: 165) in KB buffer (PBS + 0.1 % Tween-20 + 1% BSA).

4. The compound according to any one of claims 1 to 3, wherein said compound further comprises a targeting moiety.

5. The compound according to any one of claims 1 to 4, wherein said targeting moiety is capable of specifically binding to a tumor-associated antigen.

6. The compound according to any one of claims 1 to 5, wherein said compound comprises an antibody Fc region competent in Fc receptor binding.

7. A pharmaceutical composition comprising the compound according to any one of claims 1 to 6.

8. The compound according to any one of claims 1 to 6 or the pharmaceutical composition according to claim 7 for use as a medicament.169

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