Technology

OmniRat, OmniFlic, OmniMouse and OmniChicken use newly patented technology and deliver fully human OmniAb antibodies with high affinity, specificity, expression, solubility and stability. While transgenic mice expressing human antibodies date back to the 1990's, in recent years OMT and Crystal scientists were the first to create a rats and chicken expressing diversified repertoires of antibodies with fully human idiotypes. OmniMouse complements that to form the industry's only platform with three species.

In OmniRat and OmniFlic, endogenous expression of rat immunoglobulin genes was inactivated using transient expression of a zinc-finger nucleases in single-cell rat embryos. IgM, IgG, IgE and IgA analyses demonstrated no detectable levels of rat Ig in our homozygous knockout animals. This important breakthrough was featured in the journal Science in July 2009.

OmniRat produces a diverse repertoire of antibodies with human idiotypes and similar immunological characteristics as rat antibodies from wildtype animals. As published in Journal of Immunology and Journal of Immunological Methods in 2013, OMT and Pfizer scientists have demonstrated that OmniRat:

  • Contains functional recombinant immunoglobulin loci.
  • Rearranges functional human Ig genes.
  • Uses genes with similar frequency as humans.
  • Shows normal human CDR3 length.
  • Employs normal B cell development.
  • Has high expression of immunoglobulins.
  • Displays normal hypermutation and affinity maturation.

OmniFlic is a rat with a single rearranged VkJk light chain and the same heavy chain transgene as OmniRat. Antibodies from OmniFlic comprise a single germline Vk sequence and can be generated through comprehensive analysis of the heavy chain repertoires without any use of hybridoma technology.

OmniMouse was engineered with the same transgenes as OmniRat. Unlike some other transgenic mice on the market and in development, OmniMouse has freedom to operate. OmniMouse expands the epitope coverage of OmniRat and creates the potential for even broader antibody discovery of single antibodies or antibody cocktails.

OmniChicken was engineered using germ cell derived cell lines, which contribute to egg and sperm after long-term culture. Endogenous chicken immunoglobulin genes were replaced with corresponding human genes by homologous recombination. In OmniChicken a diverse repertoire of antibodies with human idiotypes is generated by gene conversion. Due to the large phylogenetic distance between birds and mammals, many target antigens that are not immunogenic in rats or mice induce a strong antibody response in immunized chickens.

The generation of therapeutic antibodies is limited by the diversity of antibody platforms. Therefore, combination of several species and genetic backgrounds increases the probability of success of antibody discovery, in particular with difficult targets.

Ligand is the only company in the world with three species and continues to develop OmniAb-enhancing technologies, which is made available to its partners as it becomes available.

Partners

Merck
Pfizer
Celgene
Amgen
Genmab
Janssen
FivePrime
Aptevo Therapeutics
SeattleGenetics
Symphogen
Armo Biosciences
Hanall Pharmaceutical
Gloria Pharmaceuticals
Tizona
ABBA
F-star
Gilead
Ono
AbbVie
BlueBirdBio
Charite
Genentech
Roche
Teneo
Teva
xCella
Surface Oncology

OmniAb is partnered with a range of large and small biopharmaceutical companies globally. For more information, including regarding OmniAb platform access, please E-mail omniab@ligand.com.