Erratum: Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15.

This corrects the article DOI: 10.1038/nature24042.

Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15.

Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand. Recent studies have identified brain areas outside the hypothalamus that are activated under these 'non-homeostatic' conditions, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive.

Comparative immunogenicity assessment: a critical consideration for biosimilar development.

An appropriate assessment strategy with validated anti-drug antibody (ADA) assays is critical for comparative evaluation of immunogenicity between a proposed biosimilar and its reference product. The strategy should aim to identify potential differences in immune responses between these products. While an ADA assay employing the proposed biosimilar product as the detecting reagent has been generally recommended for such evaluation, a product-specific assay using the product of interest may be of use as it offers a capability of detecting antibodies against specific epitopes from the respective product.

Monoclonal antibody expression in mammalian cells.

In the past two decades, the production levels for monoclonal antibodies in mammalian expression systems have improved dramatically. Single cell productivity for monoclonal antibodies has increased 20-50 fold due to the improvements in expression hosts, expression vectors, cell culture media, and production processes. However, most of these improvements are proprietary to large pharmaceutical/biotech companies and involve large steel-tank bioreactors.

Mammalian cell surface display of full length IgG.

Display technology has been developed and widely used in antibody screening and selecting. While phage can only display antibody fragments, mammalian cells can display not only fragments but full-length antibodies. Here we described the display of full length antibody on the surface of 293 cells.

A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR and attenuates PCSK9-mediated reduction in LDLR protein levels, thereby increasing LDL uptake.

Defining dose-response relationships in the therapeutic blockade of B7RP-1-dependent immune responses.

The ICOS (Inducible T cell Co-Stimulator)/B7RP-1 (B7-related protein 1) interaction is critical for the proper activation of a T lymphocyte. In this manuscript we describe a systematic in vivo approach to determine the level of blockade required to impair the generation of a T cell-dependent antibody response. We have developed an overall strategy for correlating drug exposure, target saturation, and efficacy in a biological response that can be generalized for most protein therapeutics.