A61K47/6835

Biodegradable Amphiphilic Polymer, Polymer Vesicle Prepared Therefrom and Use in Preparing Target Therapeutic Medicine for Lung Cancer
20200062897 · 2020-02-27 ·

Disclosed in the present disclosure is a biodegradable amphiphilic polymer containing disulfide in the side chain, a self-crosslinked polymeric vesicle thereof and an application in the targeted therapy of lung cancer. The polymer is obtained by an activity-controllable ring-opening polymerization based on a cyclic carbonate monomer containing a functional group of dithiolane ring, which has a controllable molecular weight and a narrow molecular weight distribution, and does not require processes of protection and deprotection; the polymer obtained by the ring-opening polymerization of the cyclic carbonate monomer of the present disclosure has biodegradability and can be used to control the drug release system, the prepared lung cancer-targeted reduction-sensitive reversibly-crosslinked polymeric vesicle as a nanomedicine carrier supports stable long circulation in vivo. However, it is highly enriched in lung cancer tissues, enter cells efficiently, and rapidly decrosslinks in the cells to release drugs, so as to kill cancer cells with high potency and specificity and inhibit the growth of tumor effectively without causing toxic and side effects.

Anti-wall teichoic antibodies and conjugates

The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

METHOD FOR PRODUCING DELIVERY VESICLES

The present invention concerns the development of vesicles that could be used for generation of vaccines or as compound delivery vehicles. More specifically, the invention relates to a method for preparing a vesicle comprising the steps of: providing recombinant Trypanosoma brucei cells expressing sortaggable VSG, treating said cells in hypotonic solution in the presence of at least one protease inhibitor until the cells are lysed, isolating the cellular membranes from the solution, suspending the isolated membranes previously obtained in a isotonic solution, treating the suspended cellular membranes obtained in the previous step with sonication in order to obtain a vesicle suspension, removing aggregated membranous debris from the vesicle suspension previously obtained, separating the vesicle suspension into populations of vesicles, and providing vesicles from a population of vesicles which is characterized by the following parameters: (i) having a single predominant protein revealed after Coomassie staining an SDS PAGE that has an apparent molecular weight of 55 to 60 kDa, (ii) having a spherical appearance in electron micrographs and (iii) exhibiting a homogenous surface structure in electron micrographs. Moreover, the present invention also relates to a vesicle comprising sortaggable VSG characterized by the aforementioned parameters as well as such a vesicle for use in treating and/or preventing a disease or medical condition or as a compound delivery vesicle, preferably, drug delivery vehicle, more preferably, nucleic acid delivery vesicle. Finally, the invention contemplates a kit for carrying out the method of the present invention comprising recombinant Trypanosoma brucei cells expressing sortaggable VSG and at least one agent for carrying out the method of the present invention or a kit comprising the vesicle of the present invention.

TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS HAVING A PYRIDINE OR PYRAZINE MOIETY, CONJUGATES THEREOF, AND METHODS AND USES THEREFOR

Compounds having a structure according to formula (I)

##STR00001##

where R.sup.1 and Ar are as defined herein, are agonists for the Toll-like receptor 7 (TLR7) and can be used as adjuvants for stimulating the immune system. Some such compounds can be used in conjugates for targeted delivery to the organ or tissue of intended action.

HYBRID IMMUNOGLOBULINS WITH MOVING PARTS
20200032272 · 2020-01-30 ·

Hybrid immunoglobulines containing moving parts are provided as well as related compositions and methods of use and methods of production. In addition, analogous genetic devices are provided as well as related compositions and methods of use and methods of production.

NANOPARTICLES

This application relates to nanoparticles, including nanoparticles derived from a plasma, and their use in the formation of conjugates. The nanoparticles can be stably conjugated to a wide variety of second species, forming conjugates which can be used, for example, in therapeutic, diagnostic and experimental methods.

CARRIER-FREE BIOLOGICALLY-ACTIVE PROTEIN NANOSTRUCTURES
20200016238 · 2020-01-16 ·

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Matriptase and u-plasminogen activator substrates and other cleavable moieties and methods of use thereof

The invention relates generally to polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator (uPA), to activatable antibodies and other larger molecules that include the cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator, and to methods of making and using these polypeptides that include a cleavable moiety that is a substrate for at least one protease selected from matriptase and u-plasminogen activator in a variety of therapeutic, diagnostic and prophylactic indications.

AN ANTIBODY FRAGMENT BASED ANTIFUNGAL CONJUGATE SELECTIVELY TARGETING CANDIDA

The present invention provides a novel antibody fragment based antifungal conjugate selectively targeting Candida spp. comprising of at least one antimicrobial peptide at one end of the conjugate, more particularly, human Histatin-5; an antibody fragment at the other end of the conjugate, specific against Candida spp. enolase, a virulence factor protease and biofilm specific antigen of Candida spp.; at least one signal protease cleavage sequence susceptible to cleavage by virulent protease secreted by Candida spp., secreted aspartyl proteinase-1 (SAP1); and at least one flexible polypeptide linker. The signal protease cleavage sequence and the flexible polypeptide linker are in tandem with each other and placed in between the antimicrobial peptide and the antibody. The in vitro MIC-99 of the conjugate against Candida spp., is in the range of 0.2-0.3 ?M, more specifically, 0.25 ?M or 250 nM.

AN ANTIBODY FRAGMENT BASED ANTIMICROBIAL CONJUGATE SELECTIVELY TARGETING PSEUDOMONAS

The present invention relates to a novel antibody fragment based antimicrobial conjugate selectively targeting Pseudomonas spp., preferably Pseudomonas aeruginosa, comprising of at least one antimicrobial peptide at one end of the conjugate preferably human Histatin-5; at least one antibody fragment at the other end of the conjugate, preferably a VHH targeting C4 decarboxylase transporter antigen of Pseudomonas aeruginosa; at least one protease cleavage sequence, preferably susceptible to cleavage by Pseudomonas aeruginosa specific virulent protease, Elastase B, and at least one flexible polypeptide linker in tandem with the protease cleavage sequence, and the protease cleavage sequence and the flexible polypeptide linker placed in between the antimicrobial peptide and antibody fragment. The antibody fragment-based antimicrobial conjugate has an in vitro MIC-99 against Pseudomonas aeruginosa of 0.5 ?M, and MIC-50 less than 0.125 ?M. It can be easily manipulated for generating next generation of conjugates in case of emergence of drug-resistant forms of the pathogen.