Overview

Advantage

Case study

Benefit

Process

Single domain antibody overview

In 1993, Hammers Casterman from Vrije Universiteit Brussel first reported that there was another type of antibody in addition to the traditional IgG antibody in camel blood. This antibody lacks the whole light chain and also the CH1 region of the heavy chain, it is called the heavy chain antibody (HcAb).

Single-domain antibody usually consists of only 110-130 amino acids of the variable region of the heavy chain antibody, with a molecular weight of only 12-15 kDa, which is much smaller than the traditional intact antibody (150-160 kDa), but it can possess similar or even higher specificity and affinity than traditional antibodies.

Because Single-domain antibody is small, highly stable, affinity-high, easy to be recombinantly expressed, easy for humanization, and easy to be fused with other antibodies, so it has attracted much attention after being discovered. After more than 20 years of research, Single-domain antibodies have been gradually applied in various fields such as immunological research, diagnostic application, medical and biological imaging, and therapeutic antibody development. Especially in 2018, the first single-domain antibody Caplacizumab from Ablynx company was approved for marketing, and a lot of antibodies were also available at various stages of clinical phases, these all demonstrated the druggability of domain antibodies, and it also marks that nanobodies will become a novel form of therapeutic antibody for the treatment of various diseases.

As an innovative antibody drug research and development company, SanyouBio has single-domain antibody generation platforms with independent intellectual property rights, and we expected to provide superior single-domain antibody candidates for therapeutic antibody related pharmaceutical companies around the world.

Another type of antibody in addition to the traditional IgG antibody in camel blood. This antibody lacks the whole light chain and also the CH1 region of the heavy chain, it is called the heavy chain antibody (HcAb).

◆ Alpaca-derived naïve library

✔ Nearly 200 samples of Alpaca PBMC

✔ Sub-trillion library size (1010 cfu)

✔ 50-100 binders at average

✔ Applicable for challenging and intractable targets

✔ Affinity KD reaches sub-nM

◆ Alpaca-derived immune library

✔ Super complete primer design

✔ Library capacity reaches 5x108/ project

✔ Affinity KD reaches pM level

✔ Suitable for bispecific Ab development

◆ Alpaca-derived semi-synthetic library and synthetic library

✔ Adopt world leading Trim primer technology

✔ The library capacity will be up to 1012 cfu

✔ Using the backbone with highest druggability

✔ Based on big data analysis, combination the CDR from super size naïve library

 Single domain antibody

◆ Characteristics

✔ Small and flexible to other fragments

✔ Highly stable

✔ Highly homologous to human germline

✔ As high as pM affinity level

✔ 5-10 higher yield than common IgG

Advantages



Panning process against targets

A chance of 100+ leads generated for any targets.

Always through 2-3 rounds of panning, as high as more than 100 binders with unique sequences could be acquired from alpaca derived antibody library, and their affinity could reach as high as pM by Fortebio method. The Elisa affinity ranking of selected candidates screened from the immune library is shown.


Fig. 1 Affinity ranking of the candidates screened out from alpaca-derived immune library by ELISA method.

► Various antibody libraries

► Solution based high through out screening

► Over 100 binders for each target

► Sequence clear after screening

► High affinity

Sanyou has established a variety of antibody screening methods such as antigen coated immuno-tube, antigen conjugated magnetic beads, and cell-based antibody screening. A suitable antibody screening method can be selected according to the characteristics of the antigen target.The magnetic beads based screening method is shown below.


  Fig. 2 The process how we screen out the candidates from our library against the interested antigen.

Case study 1


Background

Protein X2 is highly similar to X1, they have only few difference with each other, it is very hard to develop a antibody specifically recognized X2 other than X1.


Fig. 3a

                Fig. 3b

Fig. 3 Specificity test of the candidate antibodies by FACS binding on X2 stable cell line (Fig. 3a) and X1 stable cell line (Fig. 3b)


Fig. 4 Complement-Dependent Cytotoxicity (CDC) effect of one of the screened lead antibody and reference antibody (pAb)

Fig. 5 antibody-dependent cell-mediated cytotoxicity (ADCC) effect of one of the screened lead antibody and reference antibody (pAb)


Results

More than 120 sAb screened from alpaca immune-library,and 40 of them specifically recognized X2. Several sAb were confirmed similar or even betterbiological activity than Benchmarker.

Case study 2


Background

The ligand has two receptors, it is very difficult to develop an antibody to block the binding with both receptors.


Fig. 6. Affinity ranking of the candidates screened out from alpaca-derived immune library by ELISA method

Fig. 7. Blocking effect of the antigen binding with its receptor 1 by ELISA method


Fig. 8. Blocking effect of the antigen binding with its receptor 2 by ELISA method



Results

More than 120 sAb screened from alpaca immune-library,and 40 of them specifically recognized X2. Several sAb were confirmed similar or even betterbiological activity than Benchmarker.

Benefit of single domain antibody platform

Our single domain antibody platform shows overwhelming advantages compared to other platforms.


Service and technical process




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