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Obtaining accurate data on antibody stability is crucial for drug development and typically gathered in PK studies using non-human primates, which can be expensive and time consuming. Our genetically-humanized FcRn mice provide translational pharmacokinetic (PK) data for antibody-based therapeutics, Fc variants, and albumin conjugates. The humanized PK platform (HuPK™) can produce predictive data such as half-life, clearance values, area under the curve (AUC), and volume of distribution (Vd) to help you derive the optimal first-in-human (FIH) dose for candidate therapeutics.
Well established and thoroughly characterized human FcRn mice have been used to generate translationally-relevant PK data for thousands of therapeutic antibody candidates, reducing the risk of clinical trial failures and accelerating the path to regulatory approval. Our Pre-Clinical Service has decades of expertise in executing in vivo PK and pharmacodynamic (PD) studies and has well established assays to quantify test article plasma concentrations to derive PK/PD data.
|
Type of Antibody |
Therapeutics screened in FcRn Models |
|---|---|
|
Human IgG Antibody, all isotypes |
Yes |
|
Fc Recombinant Proteins |
Yes |
|
Chimeric |
Yes |
|
Bispecific Antibodies |
Yes |
|
Antibody-Drug Conjugate (ADC) |
Yes |
|
Human Albumin or Conjugates |
Yes |
|
Fc Fusion Proteins |
Yes |
|
Antibody Therapy Modality or Mechanism |
Yes |
|
Therapies Targeting FcRn function |
Yes |
|
Other Antibody isotypes (IgA, D, E, M) |
No |
Humanized FcRn mice provide PK data comparable to nonhuman primates and human values using allometric scaling.
Simple study design that can be executed within 3-4 week periods and cost significantly less than NHP studies.
The HuPK platform improves candidate selection for researchers, boosting success rates and speeding up therapeutic development.
Antibody therapeutics offer incredible versatility for treating diseases ranging from Cancer, Autoimmunity, Infectious agents, Alzheimer's and Metabolic Disorders. Our HuPK platform is as versatile as the antibodies themselves, with a range of models to address your therapeutic's specific configuration and mode of action, and the research questions you need to answer.
Let our experts help you select a model to address anti-drug antibody (ADA) response, human albumin conjugation, half-life extended antibodies or more refined PK data to assist in lead selection.
| Model | Characteristics | Main Application | Model Features |
|---|---|---|---|
|
hFcRn Tg32 (014565) |
The most validated model on the market for therapeutic antibody PK prediction. |
Prediction of the clinical half-life of therapeutic antibodies through allometric scaling. |
Physiological expression of the human FCGRT gene coding for the FcRn protein. |
|
hFcRn Tg32 SCID (018441) |
No ADA response to humanized molecules, allowing PK and PD evaluation of highly engineered molecules. |
Prediction of the clinical half-life of antibody-based molecules with strong immunogenicity in mice (i.e., Fc-fusion bispecific antibodies.) |
Physiological expression of the human FCGRT gene and lack of mature B cells. |
|
Tg32-hFc (029686) |
Expression of human IgG1 in place of mouse IgG1. |
Provides concentration steady state human IgG1 as a PD readout when FcRn is therapeutically targeted. |
Physiological relevant expression of human IgG1. |
|
hFcRn Tg276 (004919) |
Lower FcRn function compared to Tg32 that is highly correlated with human PK outcomes. |
Provides PK differentiation for test molecules not distinguished by Tg32, and shorter in-life PK studies especially for long-lived Fc variants. |
Ubiquitous expression of the human FCGRT gene coding for the FCRN protein. |
|
NSG hFcRn Tg32 (028615) |
Human FcRn Tg32 expression in mice routinely engrafted with human cells. |
These Tg32 mice can be engrafted with human CD34+ hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), patient derived xenografts (PDX), or adult stem cells and tissues. |
While PK yielded correlates with human PK, FcRn function is diminished due to unique FcgR expressed by NSG. |
|
hFcRn Tg32 Alb KO (025201) |
Features mouse albumin deficiency and human FcRn Tg32 function. |
Characterizes PK of human albumin-formatted therapeutics in the absence of high affinity mouse albumin. |
KO of mouse Alb gene removes this high affinity competition for human FcRn protection of albumin-formatted therapeutics. |
|
hFcRn Tg32 hAlb (037524) |
Model expresses both human FcRn and human serum albumin. |
Evaluate PK of albumin-formatted drugs in the presence of endogenous human albumin, and off-target PD responses of FcRn targeted therapies. |
Model expresses human serum albumin at physiological steady state 25 to 40 mg/ml. |
Tg32 mice, humanized for FcRn, provide a superior pre-clinical model for predicting human PK: Always better than wild-type B6 mouse PK, even matching nonhuman primate PK.
Data from Tg32 mice is highly correlated with human PK across many dozens of antibodies as shown here from JAX Pre-Clinical Services and from multiple publications. Allometric scaling of PK parameters yielded from Tg32 mice easily predicts clinical PK.
Through hundreds of PK/PD studies by JAX Pre-Clinical Services, and from dozens of publications over the past 20+ years, Tg32 mice have demonstrated that human FCGRT gene expression in Tg32 mice yields data that translates exceptionally well to the clinic.
Delve into Roche's integration of humanized mice into their preclinical drug development pipeline to assess the safety and efficacy of their CD19-CD28 bispecific. In this blog, we focus on their use of FcRn mice to reliably predict human PK to calculate a safe starting dose for their Phase 1 clinical trial.
Watch the Humanized Mice Pubcast
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