Molecules with specificity for CD79 and CD22
The present disclosure relates to multispecific molecule comprising a binding domain specific to the antigen CD22 and a binding domain specific to the antigen CD79a and/or CD79b, compositions comprising the same and use of both in treatment, for example the treatment of autoimmune disease.
1. A multispecific molecule comprising a binding domain specific to human antigen CD22 and a binding domain specific to human antigen CD79b,
wherein the binding domain specific to human CD22 comprises:
3 heavy chain CDRs comprising SEQ ID NO: 98, or SEQ ID NO: 98 wherein the Cys has been replaced with Ser for CDRH1, SEQ ID NO: 99, or SEQ ID NO: 99 wherein the Cys has been replaced with Ser for CDRH2 and SEQ ID NO: 100 for CDRH3 and 3 light chain CDRs comprising SEQ ID NO: 95 for CDRL1, SEQ ID NO: 96 for CDRL2 and SEQ ID NO: 97 for CDRL3; or
3 heavy chain CDRs comprising SEQ ID NO: 108, or SEQ ID NO: 108 wherein the Cys has been replaced with Ser for CDRH1, SEQ ID NO: 109, or SEQ ID NO: 109 wherein the Cys has been replaced with Ser for CDRH2 and SEQ ID NO: 110, or SEQ ID NO: 110 wherein the Cys has been replaced with Ser for CDRH3 and 3 light chain CDRs comprising SEQ ID NO: 105 for CDRL1, SEQ ID NO: 106 for CDRL2 and SEQ ID NO: 107 for CDRL3; or
3 heavy chain CDRs comprising SEQ ID NO: 118 for CDRH1, or SEQ ID NO: 118 wherein the Cys has been replaced with Ser for CDRH1, SEQ ID NO: 119, or SEQ ID NO: 119 wherein the Cys has been replaced with Ser for CDRH2 and SEQ ID NO: 120 for CDRH3 and 3 light chain CDRs comprising SEQ ID NO: 115 for CDRL1, SEQ ID NO: 116 for CDRL2 and SEQ ID NO: 117, or SEQ ID NO: 117 wherein the DS motif is substituted with EA, DA or DT and/or the DG motif is substituted with EG, DA or DS for CDRL3; or
3 heavy chain CDRs comprising SEQ ID NO: 148 for CDRH1, or SEQ ID NO: 148 wherein the Cys has been replaced with Ser, SEQ ID NO: 149, or SEQ ID NO: 149 wherein the Cys has been replaced with Ser and/or the NS motif is substituted with NA or NT for CDRH2 and SEQ ID NO: 150 for CDRH3 and 3 light chain CDRs comprising SEQ ID NO: 145 for CDRL1, SEQ ID NO: 146 for CDRL2 and SEQ ID NO: 147 for CDRL3; and
wherein the binding domain specific to human antigen CD79b comprises:
3 heavy chain CDRs comprising SEQ ID NO: 78 for CDRH1, SEQ ID NO: 79 for CDRH2 and SEQ ID NO: 80 for CDRH3 and 3 light chain CDRs comprising SEQ ID NO: 75 for CDRL1, SEQ ID NO: 76 for CDRL2 and SEQ ID NO: 77, or SEQ ID NO: 77 wherein one or both of the Cys residues have been replaced with Ser for CDRL3; or
3 heavy chain CDRs comprising SEQ ID NO: 88 for CDRH1, SEQ ID NO: 89 for CDRH2, and SEQ ID NO: 90 for CDRH3 and 3 light chain CDRs comprising SEQ ID NO: 85 for CDRL1, SEQ ID NO: 86 for CDRL2 and SEQ ID NO: 87, or SEQ ID NO: 87 wherein the DG motif is substituted with EG, DA or DS for CDRL3.
2. The multispecific molecule according to claim 1 , wherein the molecule is bispecific or trispecific.
3. The multispecific molecule according to claim 1 , wherein the molecule is a fusion protein.
4. The multispecific molecule according to claim 1 , wherein the molecule is selected from diabody, scdiabody, triabody, tandem scFv, FabFv, Fab′Fv, FabdsFv, Fab-scFv, Fab-dsscFv, Fab-(dsscFv)2, diFab, diFab′, tribody, tandem scFv-Fc, scFv-Fc-scFv, scdiabody-Fc, scdiabody-CH3, Ig-scFv, scFv-Ig, V-Ig, and Ig-V.
5. The multispecific molecule according to claim 1 , wherein each binding domain is monospecific.
6. The multispecific molecule according to claim 1 , wherein the multispecific molecule comprises no more than one binding domain which is specific to CD22 and no more than one binding domain which is specific to CD79b.
7. The multispecific molecule according to claim 1 , wherein the binding domain which is specific to CD22 and the binding domain which is specific to CD79b are independently selected from a Fab, scFv, Fv, dsFv and dsscFv.
8. The multispecific molecule according to claim 1 , in which the binding domains are humanised.
9. The multispecific molecule according to claim 1 , which further comprises a binding domain specific to serum albumin.
10. A composition comprising one or more multispecific molecules according to claim 1 and a pharmaceutically acceptable excipient, diluent or carrier.