SMALL MOLECULE ANTIBODIES

Raise a specific anti-small molecule antibody in 8 weeks thanks to our unique anti-hapten antibody production platform! Find the best way to interact with small molecules thanks to our wide range of possibilities: monoclonal antibodies generation by hybridoma or phage display, bispecific antibodies, polyclonal antibodies… Don’t miss the opportunity to get your perfect small molecule antibody!

Applications of small molecule antibodies

Small molecule antibodies are gaining more and more interest in the antibody development field, especially for their diagnostic and therapeutic applications.

Small Molecule Antibodies As Detection Tools

Small molecule antibodies are particularly appreciated in various fields, for example in food safety and environmental monitoring. Small molecules include a wide variety of compounds such as pesticides, drugs, toxins, lipids, amino acids… which can all be detected by physico-chemical technics such as chromatography or coupled chromatography-mass spectroscopy. However, the use of these methods requires expensive material as well as highly skilled staff with chemistry as well as biology backgrounds. Small molecules antibodies allows the detection, visualization (immunofluorescence, immunochemistry) and even quantification (ELISA assay) of small molecules at low cost and high sensitivity.

Small Molecule Antibodies For Therapeutic Applications

Anti-hapten antibodies are also particularly interesting in the therapeutic field and their applications could represent an alternative solution to the use of antibody-drug conjugates (ADC). Several applications of these entities have already been described:

• Small molecules are generally characterized by fast renal clearance leading to low therapeutic efficacy. That’s why, small molecule antibodies were already used to modulate pharmacokinetics of those compounds. Different options are available to modulate the pharmacokinetic properties of small molecules:
  • Link the payload in a non-covalent manner: This construct leads to hapten antibody-payload complexes and is characterized by a sustained release of the payload. The release of the payload is defined by the dissociation rate of the anti-hapten antibody-payload couple. In this case, the payload (and the antibodies) can switch from the free form to the bounded form. The strength of this interaction between the small molecule antibody and the payload can be adapted to modulate the pharmacokinetic properties of small molecules.
    • Covalent linkage between the antibody and the payload: In anti-hapten antibody-payload complexes, the release of the payload leads to faster clearance of the payload compared to the antibody. A solution to overcome this problem is to covalently link the payload to the antibody via a disulfide bridge. Creating antibody-payload conjugates allows to obtained payload serum half-life comparable to those obtained for full length IgGs. Moreover, it has been observed that the reduction of the disulfide bridge occurs once the bispecific antibody is delivered into the cell allowing the release of the payload.

• Small molecule antibodies can be used to deliver the payload to the right target. This can be done by using bispecific antibodies. Two approaches exist:
  • In the first one, the anti-hapten antibody-payload complex is pre-formed. One example of “anti-hapten antibody-small molecule hybrid” is the conjugation of DUPA, a small molecule ligand used to treat prostatic cancer, with a Fab targeting CD3.
  • The second strategy implies two phases: in the first step, the bispecific antibody is administered alone without the payload in order to reach its target. The payload is delivered in a second phase to be captured by the bispecific antibodies on the desired target.

Antibody production for small molecules antibodies

Small molecules do not represent good immunogens mainly due to their small size. Generating antibodies against small molecules necessitates small molecules to become immunogenic. To do so, chemical entities are conjugated to a carrier molecule. Thus, the design of an optimized hapten-carrier conjugates represent a major step in the successful generation of antibodies.
Several aspects have to be taken into account when designing a hapten-carrier conjugate. This includes the choice of:

• The carrier: The chosen carrier should be immunogenic and contain a sufficient amount of amino acids with reactive side chains to conjugate small molecules. Also, the origin species of the carrier should be different than the immunized animal.
• The coupling strategy: The coupling strategy is defined depending on the reactive sites present on the hapten and on the carrier as well as on the desired hapten orientation.
• The optimal hapten-carrier density: The hapten density of the conjugate influences the immune response against the antigen. The optimal density will depend on the nature of the final application and on the structure of the molecule.
• The spacer: The length of the spacer limits the sterical hindrance and helps to enhance the hapten-carrier conjugate immunogenicity. Thus, the choice of the best spacer is also of critical importance when design a small molecule antigen.