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Antibody Drug Discovery Overview

Antibody Drug Discovery Process

The overall discovery process for Ab therapeutics can be broadly divided into five stages:

Often time, screening, hit generation & lead selection are also collectively referred to as “Lead Discovery”. Activities leading up to the selection of the clinical candidate are referred to as “preclinical” work/research. While the language and choice of words changes from one publication to another, the concept remains the same.

Antibody Drug Discovery Overview

Figure 1: Overview of discovery process for therapeutic antibodies leading to the selection of a clinical candidate is shown in the workflow above. Key activities at each of the five stages are listed in the text boxes.

But how does one decide whether to pursue Ab or small molecule?

The answer is that it depends on the target. Small molecules penetrate the cell whereas large molecules (Ab therapeutics) typically target cell surface molecules like receptors or tumor antigens. And hence research will dictate what kind of intervention is required in a particular disease pathway. See major differences between small molecule and large molecule research in the table below.

Table 1: Small molecule drugs vs large molecule drugs.

Small Molecule Drugs Large Molecule Drugs
Differences
Antibody Drug Discovery OverviewSmall
LargeAntibody Drug Discovery Overview
Organic or metallic compounds that can bind proteins inside the body thereby altering their function in diseases
Biological molecules (proteins, monoclonal antibodies, vaccines etc.)
Produced using synthetic chemistry
Usually produced using recombinant DNA technology inside living cells
Small size <1,000 Daltons
Large size ~150,000 Daltons
Work inside the cell
Bind cell surface receptors
Less specific
Highly specific
Easier to deliver [often oral]
Delivery is difficult [usually thorough injection]
Relatively cheaper to manufacture
Manufacturing expensive
Easier to replicate [generics]
Difficult to replicate [biosimilars]
Example: Aspirin
Example: Somatropin, hGH, mAb

The previous section in this series is “Antibody Formats”. To review, click here.

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