Antibody Humanization

The YUMAB® humanization platform provides two technologies for the humanization of animal-derived antibodies of any source (B-cells, Hybridoma cultures, antibody sequences) by:

  • Germline-optimized CDR grafting
  • Template-driven chain shuffling

Germline-optimized CDR grafting:

Goal: Reduction of non-human sequences to a minimum and preservation of the binding properties of the parental antibody.

Principal: Yumab’s proprietary in-silico humanization tool identifies non-human amino acids in the VH and VL framework regions and replaces those with the human counterparts. Usually, for each domain different degrees of humanization are targeted (low, medium and high). Simultaneously, unwanted motifs (PTM, hydrophobic patches) can be removed. The optimized VH and VL sequence variants are combined individually with each other and produced in the final antibody format by mammalian cells. To identity functional antibodies with highest humanness, the antibody binding characteristics and biochemical properties are measured and correlated with the human germline identity.

Advantage: Preserves parental CDRs

Disadvantage: Potential CDR related IP issues with humanized version

  • Template-driven chain shuffling

Goal: Generation of an entirely novel, fully human antibody with similar or improved characteristics.

Principle: In a first step, the non-human VH domain is cloned into YUMAB® library vectors containing the full human VL repertoire. Vice versa, the non-human VL domain is cloned into YUMAB® library vectors that contain the full human VH repertoire. Since only one chain is replaced at a time, most antibodies from these hybrid libraries bind to the same or a similar epitope as the non-human antibody template. Subsequently, hybrid antibodies against the target structure are selected in-vitro.

In a second step, the human VH and VL domains of the selected antibodies are isolated and shuffled with each other, generating a new library of fully human antibodies. Again, most antibodies bind to the same or similar epitope as the non-human template. After a final antibody discovery against the target structure, the fully human antibodies are sequence analyzed, functionally tested and compared to the non-human antibody.

Advantage:

  • Novel, fully human antibody sequences (no CDR related IP issues)
  • Same or similar epitope
  • Different or improved functional properties

Contact

YUMAB GMBH
Science Campus Braunschweig-Süd
Inhoffenstr. 7
38124 Braunschweig – Germany

Email: info@yumab.com
Phone: +49 531 481170-0