The present disclosure provides polypeptides of netrin G1 (NetG1) and its cell surface receptor netrin G1 ligand (NGL1), and antibodies thereto, and methods of making such antibodies. The disclosure also provides uses of these NetG1 and NGL1 polypeptides, and antibodies thereto, in methods of treating cancers and diseases, including chronic fibrosis, inflammation, and inflammation-related diseases.

The present invention relates to the effects of codon context and synonymous codon changes on mRNA translation and methods of increasing protein production.

The present invention relates to use of a human C3a receptor agonist in the manufacture of a medicament for the treatment or prevention of an ischemic brain injury, wherein the medicament is formulated for intranasal delivery, human C3a receptor agonist for such use, as well as devices for intranasal administration comprising a human C3a receptor agonist and kits comprising such devices.

The present invention pertains to an improved chemical synthesis method for Ahp-cyclodepsipeptides which allows straight forward and easy synthesis of tailor-made Ahp-cyclodepsipeptides. The invention further provides Ahp-cyclodepsipeptides for use as HTRA protease inhibitors and their medical use.

A vaccine construct comprising an antigenic PCSK9 peptide and an immunogenic carrier, and methods of using the same that are effective to lower blood cholesterol levels in a mammal and treat dyslipidemias and related disease states in a mammal without the frequency of administration required by passive immunity strategies.

Processes for preparing compounds of Formula (1) and Formula (2) are described, wherein X, Y, Z, R.sub.1-R.sub.7, L and n are defined herein. Intermediates useful in the preparation of the compounds of Formula (1) and Formula (2) are also described. ##STR00001##

Processes for preparing compounds of Formula (1) and Formula (2) are described, wherein X, Y, Z, R.sub.1-R.sub.7, L and n are defined herein. Intermediates useful in the preparation of the compounds of Formula (1) and Formula (2) are also described. ##STR00001##

The present disclosure relates to compounds of formula (I):

RCG1-L-P  (I)

wherein RCG1 represents a reactive chemical group being reactive towards a chemical group present on a polypeptide such as an antibody; P represents H, OH or an activated O; and L represents a specific linker. The disclosure also relates to cryptophycin payloads, as well as to cryptophycin conjugates, to compositions containing them and to their therapeutic use, especially as anticancer agents. The disclosure also relates to the process for preparing these conjugates.

The present disclosure relates to compounds of formula (I):

RCG1-L-P  (I)

wherein RCG1 represents a reactive chemical group being reactive towards a chemical group present on a polypeptide such as an antibody; P represents H, OH or an activated O; and L represents a specific linker. The disclosure also relates to cryptophycin payloads, as well as to cryptophycin conjugates, to compositions containing them and to their therapeutic use, especially as anticancer agents. The disclosure also relates to the process for preparing these conjugates.

The present invention relates to a method of forming a peptide of Formula (I) (P.sup.1-Xaa.sup.1-Xaa.sup.2-P.sup.2) by ligating a first peptide of Formula (II) (P.sup.1-Xaa.sup.1-X—R, wherein X is O or S) to a second peptide of Formula (III) (Xaa.sup.1-Xaa.sup.2-P.sup.2) by enzymatically cleaving the bond between “Asx” and “X” in the first peptide of Formula (II) and ligating the fragment P.sup.1-Asx of the first peptide to the second peptide of Formula (III), wherein the enzymatic cleavage and ligation reaction is catalyzed by butelase 1 (SEQ ID NO: 1) and the peptide of Formula (I) is a depsipeptide, preferably a thiodepsipeptide. Further encompassed are peptides and dendrimeric peptide assemblies prepared using the presently disclosed method, as well as use of the dendrimeric peptide assemblies as a vaccine, medicament, or diagnostic agent, particularly as an antimicrobial agent.