Figure 1.

Bispecific IgG Formats Reported to Enhance Brain Exposure of Proteins

(A) Tetravalent bispecific format fusing two Aβ ScFvs to the C-terminal heavy chains of a high affinity TfR antibody.¹² (B) Bivalent high or medium affinity TfR antibody fusing two payload proteins to the C-terminal heavy chains.^13,16, 17, 18 (C) Tetravalent bispecific format fusing two Aβ ScFvs to the C-terminal light chains of a therapeutic antibody.¹⁴ (D) Brain shuttle format fusing one TfR scFab to one of the IgG heavy chain.¹⁵ (E) Divalent bispecific format.²² (F) Therapeutic antibody with TfR affinity engineered in its Fc domain.²⁰ (G) Tribody format linking two anti-Aβ ScFvs to an anti-TfR Fab.²¹ (H and I) DVDs²³ and TBTIs²⁴. Blue, TfR; green, Aβ; pink, BACE1 recognizing paratopes; yellow, payload proteins such as IL-1 receptor antagonist,¹⁷ TNF-alpha decoy receptor protein,¹³ GDNF,¹⁸ or lysosomal enzymes such as iduronate sulfatase.¹⁶