Methods for treating moderate-to-severe atopic dermatitis in a pediatric subject are provided. In one aspect, the methods comprise administering to the subject one or more doses of an interleukin-4 receptor (IL-4R) antagonist, such as an anti-IL-4R antibody or antigen-binding fragment thereof.

Provided is a system (10) for determining a probability of an asthma exacerbation in a subject. The system comprises an inhaler (100) for delivering a rescue medicament to the subject. The inhaler has a use-detection system (12B) configured to determine a rescue inhalation performed by the subject using the first inhaler. A sensor system (12A) is configured to measure a parameter relating to airflow during the rescue inhalation. The system further comprises a processor (14) configured to determine a number of the rescue inhalations during a first time period, and receive the parameter measured for at least some of the rescue inhalations. The processor determines, using a weighted model, the probability of the asthma exacerbation based on the number of rescue inhalations and the parameters.

The model is weighted such that the number of rescue inhalations is more significant in the probability determination than the parameters.

The present disclosure relates to pyrrolobenzodiazepines (PBDs) having a labile C2 or N10 protecting group in the form of a linker to an antibody.

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

The present disclosure provides fusion proteins that specifically inhibit transforming growth factor-β (TGF-β) signaling in CD4+ helper T cells, and engineered CD4+ helper T cells that are deficient in TGF-β signaling, to counteract tumor-induced immune tolerance and promote anti-tumor immunity. The fusion proteins and engineered CD4+ helper T cells of the present technology are useful in methods for treating cancer, and enhancing the efficacy of other therapeutic agents against refractory cancer cells.

The disclosure provides trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. The disclosure also provides methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins.

In one aspect, the invention comprises a fusion construct comprising ALKI extracellular domain and a stability enhancing domain. In another aspect, the invention comprises an antibody that interferes with or blocks the ALKI extracellular domain binding to LDL, but does not interfere with or block the ALKI extracellular domain binding to BMP9/10. In yet another aspect, the invention comprises methods of reducing rates of LDL uptake in the endothelial cells of a patient in need thereof by administering the fusion construct or monoclonal antibodies described herein to the patient.

The disclosure provides trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. The disclosure also provides methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins.

There is described herein a method for inducing Tc22 lineage T cells from a population of CD8+ T cells, the method comprising: a) providing a population of CD8+ T cells; b) activating the population of CD8+ T cells; and c) culturing or contacting the population of CD8+ T cells with IL-6.