The Jackson Laboratory

Derry Roopenian

Shreeram Akilesh

Daniel J Shaffer

Gregory Christianson

Michael V Wiles

Kevin David Mills

Benjamin E Low

Greg Christianson

The present disclosure provides improved humanized IgG1 FCRN mouse models for use, for example, in estimating serum half-life of therapeutic proteins such as monoclonal antibodies.

Humanized mouse models of the FcRn recycling pathway

In certain embodiments, this present invention provides antibodies and Fc fusion proteins with enhanced pharmacokinetics, such as biotinylated antibodies or biotinylated Fc fusion polypeptides.

Antibodies and Fc fusion protein modifications with enhanced persistence or pharmacokinetic stability in vivo and methods of use thereof

Antibodies and FC fusion protein modifications with enhanced persistence or pharmacokinetic stability in vivo and methods of use thereof

Systems and methods for performing rapid genomic DNA analysis of samples, such as control samples and experimental samples. In one aspect, the system makes use of genomic DNA input, rather than gene expression input such as mRNA and/or cDNA associated with mRNA. The systems and methods perform statistical analyses on data generated from the samples to determine which DNA sequences in an identified set of DNA sequences have a basis of variation in an experimental sample when compared to a control sample, and additionally provide a quantitative measure of this variation. The quantitative measure may be based on metrics such as copy number and/or fold-change. The systems and methods employ this statistical framework in DNA-based evaluation settings, including the evaluation/diagnosis of a pathological condition such as cancer or transgenic analysis of transgenic plants and animals. The systems and methods also provide means to select and refine the selection of DNA sequences, such as genes, known to undergo copy change for a particular pathological condition. This leads to the creation of stock gene sets catered to individual application areas and/or clinical uses, which may be used with the systems and methods described in this application for the purpose of, for example, a clinical kit for rapid DNA-based evaluation.

Systems and methods for statistical genomic DNA based analysis and evaluation

Methods and applications of Global Patter Recognition (GPR), including a system for analyzing the results of real-time polymerase chain reaction (RT-PCR) experiments employing micro-titer and/or microarray plates and robotic plate readers is described. The system employs a set of self-normalizing housekeeping primers or oligonucleotides on the plates/arrays and an algorithmic approach to normalizing expression data from all primers on the plate based on the reaction products of several of the self-normalizing gene primers oligonucleotides. Normalization is accomplished using simplex reactions involving these self-normalizing primers/oligonucleotides; the normalization parameters are then useable across all control and experimental reactions of the plate/array. A ranked list of genes whose amount of change is statistically significant can be determined. The accuracy of this list is enhanced by the data normalization aspect of the system. Other applications of GPR are also disclosed herein.

Expression data analysis systems and methods

Disclosed is a transgenic knockout mouse whose genome comprises a homozygous disruption in its endogenous FcRn gene. The homozygous RcRn disruption prevents the expression of a functional FcRn protein, resulting in a transgenic knockout mouse in which exogenously administered IgG1 exhibits a substantially shorter half-life, as compared to the half-life of exogenously administered IgG1 in a wild-type mouse. The transgenic knockout mouse with a homozygous RcRn disruption is also unable to absorb maternal IgG in the prenatal or neonatal stage of development. Also disclosed is a transgenic knockout mouse comprising a homozygous FcRn disruption and a human FcRn transgene. The transgenic addition of human FcRn results in a substantial increase in the half-life of exogenously administered human IgG1. Methods of using the transgenic knockout mouse, and cells derived from them, are also disclosed.

Transgenic mouse expressing human FcRn protein

Disclosed is a transgenic knockout mouse whose genome comprises a homozygous disruption in its endogenous FcRn gene. The homozygous FcRn disruption prevents the expression of a functional FcRn protein, resulting in a transgenic knockout mouse in which exogenously administered IgG1 exhibits a substantially shorter half-life, as compared to the half-life of exogenously administered IgG1 in a wild-type mouse. The transgenic knockout mouse with a homozygous FcRn disruption is also unable to absorb maternal IgG in the prenatal or neonatal stage of development. Also disclosed is a transgenic knockout mouse comprising a homozygous FcRn disruption and a human FcRn transgenic. The transgenic addition of human FcRn results in a substantial increase in the half-life of exogenously administered human IgG1. Methods of using the transgenic knockout mouse, and cells derived from them, are also disclosed.

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Salisbury Cove, ME, United States of America

Derry Roopenian