Overview of Appended IgG

Bispecific antibodies (bsAbs) are engineered molecules that can simultaneously bind to two different antigens or epitopes, thereby enabling novel therapeutic strategies that are not achievable with conventional monoclonal antibodies (mAbs). BsAbs can be classified into three main formats: IgG-like, antibody fragment-based, and appended IgG. IgG-like bsAbs retain the structure and properties of natural IgG molecules, but have two different antigen-binding sites on each Fab arm. Antibody fragment-based bsAbs consist of various combinations of variable domains (VDs), single-chain variable fragments (scFvs), or Fc fragments, which are often linked by flexible peptides or chemical cross-linkers. Appended IgG bsAbs are hybrid molecules that combine an IgG molecule with one or more additional antigen-binding moieties, such as VDs or scFvs, which are fused to either the N- or C-terminus of the IgG chains.

Overview of IgG(H)-scFv

IgG(H)-scFv is another appended IgG format. It consists of an scFv fused to the C-terminus of the heavy chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The scFv can be derived from any mAb, and is connected to the IgG heavy chain by a flexible linker of about 20 amino acids. IgG(H)-scFv bsAbs have several advantages over DVD-IgG bsAbs, such as high affinity, flexibility, and ability to bind to epitopes that are inaccessible to VDs. However, IgG(H)-scFv bsAbs also have some drawbacks, such as potential aggregation, instability, and immunogenicity. Moreover, IgG(H)-scFv bsAbs may have a reduced serum half-life due to the exposure of the scFv to proteases and clearance receptors. IgG(H)-scFv bsAbs have been developed for various indications, such as cancer, inflammation, and neurodegenerative diseases.

Overview of scFv-(H)IgG

scFv-(H)IgG consists of an scFv fused to the N-terminus of the heavy chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The scFv can be derived from any mAb, and is connected to the IgG heavy chain by a flexible linker of about 20 amino acids. scFv-(H)IgG bsAbs have several advantages over IgG(H)-scFv bsAbs, such as high avidity, stability, and compatibility with standard IgG production platforms. However, scFv-(H)IgG bsAbs also have some drawbacks, such as potential interference with Fc-mediated functions, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Moreover, scFv-(H)IgG bsAbs may have a reduced serum half-life due to the exposure of the scFv to proteases and clearance receptors. scFv-(H)IgG bsAbs have been developed for various indications, such as cancer, hemophilia, and viral infections.

Overview of IgG(L)-scFv

IgG(L)-scFv consists of an scFv fused to the C-terminus of the light chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The scFv can be derived from any mAb, and is connected to the IgG light chain by a flexible linker of about 20 amino acids. IgG(L)-scFv bsAbs have several advantages over IgG(H)-scFv and scFv-(H)IgG bsAbs, such as high specificity, flexibility, and ability to bind to epitopes that are inaccessible to VDs. However, IgG(L)-scFv bsAbs also have some drawbacks, such as potential immunogenicity, instability, and aggregation. Moreover, IgG(L)-scFv bsAbs may have a reduced serum half-life due to the exposure of the scFv to proteases and clearance receptors. IgG(L)-scFv bsAbs have been developed for various indications, such as cancer, autoimmune diseases, and infectious diseases.

Overview of scFv-(L)IgG

scFv-(L)IgG consists of an scFv fused to the N-terminus of the light chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The scFv can be derived from any mAb, and is connected to the IgG light chain by a flexible linker of about 20 amino acids. scFv-(L)IgG bsAbs have several advantages over IgG(L)-scFv bsAbs, such as high affinity, stability, and compatibility with standard IgG production platforms. However, scFv-(L)IgG bsAbs also have some drawbacks, such as potential interference with Fc-mediated functions, such as ADCC and CDC. Moreover, scFv-(L)IgG bsAbs may have a reduced serum half-life due to the exposure of the scFv to proteases and clearance receptors. scFv-(L)IgG bsAbs have been developed for various indications, such as cancer, hemophilia, and viral infections.

Overview of IgG(L,H)-Fv

IgG(L,H)-Fv consists of a V fused to the C-terminus of both the light and heavy chains of an IgG molecule, resulting in a tetravalent bsAb with two pairs of identical antigen-binding sites. The V can be derived from either the heavy or light chains of mAbs, and is connected to the IgG chains by a flexible linker of about 15 amino acids. IgG(L,H)-Fv bsAbs have several advantages over DVD-IgG bsAbs, such as high avidity, stability, and compatibility with standard IgG production platforms. However, IgG(L,H)-Fv bsAbs also have some drawbacks, such as potential steric hindrance between the VDs, which may affect the binding affinity and specificity. Moreover, IgG(L,H)-Fv bsAbs may have a reduced serum half-life due to the exposure of the VDs to proteases and clearance receptors. IgG(L,H)-Fv bsAbs have been developed for various indications, such as cancer, autoimmune diseases, and infectious diseases.

Overview of IgG(H)-V

IgG(H)-V consists of a V fused to the C-terminus of the heavy chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The V can be derived from any mAb, and is connected to the IgG heavy chain by a flexible linker of about 15 amino acids. IgG(H)-V bsAbs have several advantages over IgG(H)-scFv and scFv-(H)IgG bsAbs, such as high affinity, flexibility, and ability to bind to epitopes that are inaccessible to scFvs. However, IgG(H)-V bsAbs also have some drawbacks, such as potential aggregation, instability, and immunogenicity. Moreover, IgG(H)-V bsAbs may have a reduced serum half-life due to the exposure of the V to proteases and clearance receptors. IgG(H)-V bsAbs have been developed for various indications, such as cancer, inflammation, and neurodegenerative diseases.

Overview of V(H)-IgG

V(H)-IgG consists of a V fused to the N-terminus of the heavy chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The V can be derived from any mAb, and is connected to the IgG heavy chain by a flexible linker of about 15 amino acids. V(H)-IgG bsAbs have several advantages over IgG(H)-V bsAbs, such as high avidity, stability, and compatibility with standard IgG production platforms. However, V(H)-IgG bsAbs also have some drawbacks, such as potential interference with Fc-mediated functions, such as ADCC and CDC. Moreover, V(H)-IgG bsAbs may have a reduced serum half-life due to the exposure of the V to proteases and clearance receptors. V(H)-IgG bsAbs have been developed for various indications, such as cancer, hemophilia, and viral infections.

Overview of IgG(L)-V

IgG(L)-V consists of a V fused to the C-terminus of the light chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The V can be derived from any mAb, and is connected to the IgG light chain by a flexible linker of about 15 amino acids. IgG(L)-V bsAbs have several advantages over IgG(L)-scFv and scFv-(L)IgG bsAbs, such as high specificity, flexibility, and ability to bind to epitopes that are inaccessible to scFvs. However, IgG(L)-V bsAbs also have some drawbacks, such as potential immunogenicity, instability, and aggregation. Moreover, IgG(L)-V bsAbs may have a reduced serum half-life due to the exposure of the V to proteases and clearance receptors. IgG(L)-V bsAbs have been developed for various indications, such as cancer, autoimmune diseases, and infectious diseases.

Overview of V(L)-IgG

V(L)-IgG consists of a V fused to the N-terminus of the light chain of an IgG molecule, resulting in a bivalent bsAb with two different antigen-binding sites. The V can be derived from any mAb, and is connected to the IgG light chain by a flexible linker of about 15 amino acids. V(L)-IgG bsAbs have several advantages over IgG(L)-V bsAbs, such as high affinity, stability, and compatibility with standard IgG production platforms. However, V(L)-IgG bsAbs also have some drawbacks, such as potential interference with Fc-mediated functions, such as ADCC and CDC. Moreover, V(L)-IgG bsAbs may have a reduced serum half-life due to the exposure of the V to proteases and clearance receptors. V(L)-IgG bsAbs have been developed for various indications, such as cancer, hemophilia, and viral infections.

Overview of KIH-IgG-scFab

KIH-IgG-scFab consists of a single-chain Fc/ab fragment (scFab) fused to the C-terminus of the heavy chain of a knob-into-hole (KIH) IgG molecule, resulting in a tetravalent bsAb with two pairs of identical antigen-binding sites. The scFab can be derived from any mAb, and is connected to the IgG heavy chain by a flexible linker of about 20 amino acids. KIH-IgG-scFab bsAbs have several advantages over IgG(L,H)-Fv and DVD-IgG bsAbs, such as high stability, low immunogenicity, and ability to bind to epitopes that are inaccessible to VDs. However, KIH-IgG-scFab bsAbs also have some drawbacks, such as potential steric hindrance between the scFabs, which may affect the binding affinity and specificity. Moreover, KIH-IgG-scFab bsAbs may have a reduced serum half-life due to the exposure of the scFabs to proteases and clearance receptors. KIH-IgG-scFab bsAbs have been developed for various indications, such as cancer, autoimmune diseases, and infectious diseases.

Overview of 2scFv-IgG

2scFv-IgG consists of two scFvs fused to the N-terminus of both the light and heavy chains of an IgG molecule, resulting in a tetravalent bsAb with two pairs of identical antigen-binding sites. The scFvs can be derived from any mAb, and are connected to the IgG chains by a flexible linker of about 20 amino acids. 2scFv-IgG bsAbs have several advantages over scFv-(L)IgG and scFv-(H)IgG bsAbs, such as high avidity, stability, and compatibility with standard IgG production platforms. However, 2scFv-IgG bsAbs also have some drawbacks, such as potential interference with Fc-mediated functions, such as ADCC and CDC. Moreover, 2scFv-IgG bsAbs may have a reduced serum half-life due to the exposure of the scFvs to proteases and clearance receptors. 2scFv-IgG bsAbs have been developed for various indications, such as cancer, hemophilia, and viral infections.

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