This invention relates to antisense oligonucleotides comprising at least one N3′.fwdarw.P5′ phosphorodiamidate linkage (NPN) in the backbone as well as methods for using the same. The antisense oligonucleotides can effectively prevent or decrease protein expression.

The present invention provides to a bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

The invention provides compositions and methods for treating CEA-positive cancers. The method comprising administering a PD-1 axis binding antagonist and a bispecific antibody that targets CEA and CD3.

Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula:

##STR00001##

wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.

Provided herein are intermediates and processes useful for facile synthesis of compounds of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Q, P.sup.1 and P.sup.2 are as defined in this disclosure.

The present invention relates to a short peptide-based therapeutic agent and a medicinal composition including the same for inhibiting activities of cancer cells, which includes at least one short peptide listed as SEQ ID NOs: 1 and 2, either of which is unglycosylated and has no more than 40 amino acid residues, thereby specifically reducing or inhibiting activities of cancer cells such as the cancer cell proliferation, cancer stemness, cell migration, cancer cell invasion, metastasis or drug resistance.

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Embodiments of the invention provide methods of attenuating, e.g., inhibiting or reducing, cellular proliferation and migration, particularly endothelial cell proliferation and migration, including that associated with angiogenesis, as well as attenuating cancerous tumor growth and metastasis, using opioid antagonists, including, but not limited to, those that are peripherally restricted antagonists.

Compounds of formula I and their metabolites are potent mediators of an inflammatory response:

##STR00001##

where a, b, c, d, e, f, V, W, X, Y, R.sup.a, R.sup.a′, R.sup.b, R.sup.b′, R.sup.c, and R.sup.c′ are defined herein. In particular, the compounds of the invention are candidate therapeutics for treating inflammatory conditions.

Disclosed are methods for treating Vascular Leak Syndrome and preventing cancer metastasis. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, sepsis, cancer or the presence of pathogens.