Appended IgGs Generation Service for Bispecific Antibody

Creative Biolabs provides professional appended BsIgG design, construction and analysis services for your research. We have been committed to offering customers an impeccable antibody engineering platform based on brilliant technical scientists, advanced protein engineering techniques and a reliable and robust construction system which can meet each customer’s individual requirements.

Bispecific antibodies (BsAb) are artificial antibodies that bind two different antigens, or two different epitopes on the same antigen. Engineering of BsAbs opens up many new potential therapeutic applications from the fields of immunotherapy, chemotherapy, radiotherapy, and gene therapy. Appended IgGs are a group of BsAb structural groups of which conventional IgGs are appended with one or more additional antigen-binding units. That is, in appended IgGs, monospecific IgGs are engineered for bispecificity by add additional antigen-binding moieties to either the carboxy or amino termini of either heavy or light chains. The antigen-binding moieties may be Fab, scFv, Fv, single domain antibodies or engineered protein scaffolds. To produce different formats of appended IgGs, genetic engineering is the most widely used and appropriate method.

For now, there have been numerous of appended BsIgGs researched and reported, some of which have reached clinical development. The main formats of appended IgGs are listed below.

Appended IgG >150 kDa

IgG-scFv

IgG-v

Fv(H,L)-IgG 200 kDa

IgG(L,H)-Fv 175 kDa

KIH IgG-scFab 200 kDa

scFv4-Ig 200 kDa

Fab-IgG

The features of appended IgGs

• Appended IgGs are IgGs based molecules with additional antigen-binding moieties. They still reserve some characteristics of conventional IgGs including the Fc portion and the natural avidity to antigens. The IgG Fc region not only facilitates the purification but also improves the solubility and stability of BsAbs. Moreover, Fc engineering can be performed to enhance or decrease the Fc-mediated effector functions.
• For each antigen specificity, appended IgGs can be bispecific and bivalent (2+2 or 2+1 antigen-binding valency), tetraspecific and tetravalent (1+1+1+1 antigen-binding valency), etc.
• Appended IgGs can bind the antigens to all variable domains simultaneously to provide a higher specific binding capacity. Therefore, this type of BsAbs can be a potential candidate in the researches that are designed to target low abundance proteins and maybe it enables longer dosing intervals.
• The distance of two antigen-binding domains can be customized which is realized by the additional binding units at the distal end of the heavy chain.
• Appended IgGs are generated by genetic engineering which enables the molecule design to be adapted to the desired activity.
• There are more artificial linkers used in appended IgGs than that in conventional IgGs and IgGs.

According to every client’s requirements, Creative Biolabs provides customized BsAb engineering services. For more detailed information, please feel free to contact us or directly send us an online inquiry.

Reference

Spiess, C.; et al. Alternative molecular formats and therapeutic applications for bispecific antibodies. Molecular immunology. 2015, 67(2): 95-106.