Volume 129 - How are Monoclonal Antibodies Structured?

mAbs and other Fab-ulous Antibodies

What is the structure of an antibody?

Previously, we discussed the basic building blocks of an antibody and its general function. Now, we’ll dive a little deeper into the different regions of an antibody and their respective functions. Abbvie, along with most pharmaceutical companies, produce IgG antibodies composed of four polypeptide chains.

Heavy Chain Graphic

Heavy Chain (HC)

One of the two types of polypeptide chains found in IgG antibodies. Heavy chains are linked together by disulfide bonds. Depending on the type of antibody, the two heavy chain polypeptides can be identical or variable.

Fc Region Graphic

Fc Region

The base of the antibody forms the fragment crystallizable (Fc) region. This base consists of constant domains. It is the essential region for the activation of an immune response. This region can be recognized by Fc receptors on lymphocytes and other immune cells, allowing them to bind and ultimately destroy the antigen.

Light Chain Graphic

Light Chain (LC)

The light chain is the other type of polypeptide chain found in IgG antibodies. Each light chain is linked to each heavy chain by a disulfide bond. Depending on the type of antibody, these two light chains can be identical or variable.

Fab Region Graphic

Fab Region

The fragment antigen-binding (Fab) region is the variable region of the antibody. It is the part of the antibody that binds tightly to a specific part of its target antigen, called an epitope.

What types of antibodies are produced at AbbVie?

Now that we’re familiar with the different regions of antibodies, it’s time to talk about the different types of antibodies. Here at AbbVie, we have experience commercially producing Monoclonal Antibodies and Bispecific Antibodies. It is also possible to cleave an antibody so that only a fragment of the antibody is used as a drug like the Fab region. AbbVie is currently developing projects with Fabs but has no commercially approved drugs of this antibody type. Look below for more details on each type.

Monoclonal Antibody Graphic

Monoclonal Antibody (mAb)

Key Characteristics

  • Binds to only one target antigen based on Fab region
  • Identical HCs and LCs
  • Most common biologic produced in the pharmaceutical industry
Bispecific Antibody Graphic

Bispecific Antibody (BsAb)

Key Characteristics

  • Binding of antibody at two different targets simultaneously, creates more diversity of mechanisms of action
  • More difficult than mAbs both to manufacture and to test analytically (ex: Correct heavy/light chain combination, Creation of 2 separate cell lines)
Fab Graphic

Fab

Key Characteristics

  • Only contains the variable region of the antibody, prevents unwanted binding to Fc receptors
  • Prevent target from interacting with cells (ex: bind to poisons in the body)
  • Very difficult to test analytically due to its lack of the antibody region sed for purification and testing in the pharmaceutical industry

Industry Example:

Digoxin-specific Fabs are used to treat cardiotoxins that can be produced by living things like plants and toads.

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