The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

The present invention provides an in vitro method for detecting the presence of neutralizing antibodies against recombinant human insulin (rHI) in human serum. It also provides a kit for an in vitro method of detection of the presence of recombinant human insulin (rHI) neutralizing antibodies.

A method for screening compounds for their ability to interact with transmembrane proteins is provided. Also provided is a method for determining whether proteins such as transmembrane proteins are able to oligomerise.

The present invention is relevant to polypeptides and novel methods of polypeptide evolution. The present invention further relates to methods of identifying a cross-species mutant polypeptide from, or based upon, a template polypeptide.

The current disclosure provides for specific peptides from the Insulin Receptor Substrate 1 (IRS1) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying the IRS1 directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. IRS1 protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of an IRS1 peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

Specific peptides, and derived ionization characteristics of the peptides, from the Insulin Receptor protein (IR), and its isoforms IR-A and IR-B, that are particularly advantageous for quantifying the IR protein, IR-A isoform and/or IR-B isoform, directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed and are selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and the IR protein, and IR-A and/or IR-B isoforms, is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an IR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

The present invention relates to soluble monomeric Anti-Mullerian Hormone Receptor type II (AMHRII) fusion proteins and uses thereof, in particular for detection or quantification of the bioactive cleaved form of Anti-Millerian Hormone in a sample. In particular, the present invention relates to a soluble monomeric AMHRII fusion protein wherein one AMHRII extracellular domain is fused to a heterologous polypeptide. A further aspect of the present invention relates to a method for detecting or quantifying the presence of bioactive cleaved AMH in a sample, said method comprising contacting the sample with a soluble monomeric AMHRII fusion protein of the invention.

The present invention relates to soluble monomeric Anti-Mullerian Hormone Receptor type II (AMHRII) fusion proteins and uses thereof, in particular for detection or quantification of the bioactive cleaved form of Anti-Millerian Hormone in a sample. In particular, the present invention relates to a soluble monomeric AMHRII fusion protein wherein one AMHRII extracellular domain is fused to a heterologous polypeptide. A further aspect of the present invention relates to a method for detecting or quantifying the presence of bioactive cleaved AMH in a sample, said method comprising contacting the sample with a soluble monomeric AMHRII fusion protein of the invention.

Biomarkers useful for diagnosing and assessing inflammatory disease are provided, along with kits for measuring their expression. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples. The biomarkers include at least two biomarkers selected from the DAIMRK group and the score is a disease activity index (DAI).

Novel mutated humanized 12G4 antibodies, and fragments thereof, directed against the anti-Mllerian hormone type II receptor.