The invention provides compositions or pharmaceutical compositions of novel high penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. For example, HPCs of NSAIA have demonstrated indications such as treating hair loss and bold. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

The present invention provides a compound of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are as described herein. The present invention relates generally to selective FXR agonists and to methods of making and using them.

The present invention provides a compound of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are as described herein. The present invention relates generally to selective FXR agonists and to methods of making and using them.

The present invention is generally directed towards compounds capable of binding the aryl hydrocarbon receptor and modulating its activity, methods of treating inflammatory conditions such as Crohn's disease using such compounds, and pharmaceutical compositions comprising such compounds. Also provided are methods of increasing levels of IL-22 in a subject and/or decreasing levels of IFN-γ in a subject.

The present invention relates to methods for the treatment, prevention and diagnostic of diseases using compounds that specifically bind and inhibit human NKG2A in combination with compounds that bind and inhibit human PD-1. The invention also relates to assays to identify NKG2A+PD1+ tumor infiltrating NK and/or CD8 T cells.

This invention relates generally to antibodies that bind to human B and T lymphocyte attenuator (BTLA) and uses thereof. More specifically, the invention relates to agonistic antibodies that bind human BTLA and modulate its activity, and their use in treating inflammatory, autoimmune and proliferative diseases and disorders. Suitably, the antibodies also possess an Fc modification that enhances signalling through FcγR2B.

This invention relates generally to antibodies that bind to human B and T lymphocyte attenuator (BTLA) and uses thereof. More specifically, the invention relates to agonistic antibodies that bind human BTLA and modulate its activity, and their use in treating inflammatory, autoimmune and proliferative diseases and disorders. Suitably, the antibodies also possess an Fc modification that enhances signalling through FcγR2B.

Compounds may be administered to prevent or rescue organ injury following exposure to alkylating agents, such as sulfur mustards. The compounds may be substituted metalloporphyrins.

The present disclosure provides methods of administering chimeric and hybrid Factor VIII (FVIII) polypeptides comprising FVIII and Fc to subjects at risk of developing inhibitory FVIII immune responses, including anti-FVIII antibodies and/or cell-mediated immunity. The administration is sufficient to promote coagulation and to induce immune tolerance to FVIII. The chimeric polypeptide can comprise full-length FVIII or a FVIII polypeptide containing a deletion, e.g., a full or partial deletion of the B domain.

The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.