The invention relates to materials and methods of conjugating a water soluble polymer to an oxidized carbohydrate moiety of a therapeutic protein comprising contacting the oxidized carbohydrate moiety with an activated water soluble polymer under conditions that allow conjugation. More specifically, the present invention relates to the aforementioned materials and methods wherein the water soluble polymer contains an active aminooxy group and wherein an oxime or hydrazone linkage is formed between the oxidized carbohydrate moiety and the active aminooxy group on the water soluble polymer, and wherein the conjugation is carried out in the presence of a nucleophilic catalyst.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present invention provides a drug composition comprising particles comprising a biodegradable or bioerodable polymer and a drug, a soluble, biodegradable or bioerodible excipient, a bulking agent and a reconstitution aid. The invention also provides a pharmaceutical formulation and a unit dosage form of the pharmaceutical formulation. The invention provides methods of treatment of a disease or condition accordingly. The invention also provides a drug composition for use in a cannulation device.

The present invention provides a nanogel nasal vaccine that induces cell-mediated immunity. The present invention relates to a vaccine preparation comprising a complex of a nanogel, a vaccine antigen, and an adjuvant, wherein the vaccine preparation can efficiently induce the cell-mediated immunity, and can also induce a systemic and mucosal immune response.

A compound including a prodrug having a psychoactive base substance attached to an amino acid. A method of treating an individual, by administering proMDMA, a proMDMA-like compound, or proR(-)MDMA to the individual, metabolizing the prodrug, and releasing the MDMA or MDMA-like substance in the individual. A method of reducing anxiety while administering MDMA, by providing a slow release of MDMA, an MDMA-like substance or R(-)MDMA thereby reducing anxiety in the individual at the onset of administration. A method of personalized medicine, by evaluating an individual and determining if there are characteristics present that would not be suitable for MDMA treatment and administering proMDMA, a proMDMA-like substance, or proR(-)MDMA to the individual. A method of reducing abuse of MDMA, by administering proMDMA, a proMDMA-like substance, or proR(-)MDMA, and providing a delayed and attenuated effect of MDMA or a MDMA-like substance, thereby reducing abuse.

A combination therapy involving different therapeutic molecules can enhance and improve the therapeutic potentials. An effective therapeutic strategy conjugates silica (SiO.sub.2) nanoparticles with, e.g., 3-glycidyloxypropyl, trimethoxysilane and azoles, e.g., 1,2,4-triazole (Tri), 3-aminotriazole (ATri), 5-aminetetrazole (Atet), imidazole (Imi). These exemplary materials—classified as SiO.sub.2-3GPS-Tri (Conj. 1), SiO.sub.2-3GPS-Atri (Conj. 2), SiO.sub.2-3GPS-Atet (Conj. 3), SiO.sub.2-3GPS-Btri (Conj. 4), and SiO.sub.2-3GPS-Imi (Conj. 5)—can amplify targeting of therapeutics for human colorectal carcinoma cells (HCT-116), enhancing anti-cancer effects.

The invention concerns fusion proteins, wherein two endoglycosidases are fused, possibly via a linker. The fusion enzymes according to the invention have structure (1): EndoX-(L).sub.p-EndoY (1), wherein EndoX is an endoglycosidase, EndoY is an endoglycosidase distinct from EndoX, L is a linker and p is 0 or 1. Such fusion enzymes capable of trimming glycoproteins comprising at least two distinct glycoforms in a single step. The invention further concerns the use of the fusion enzyme according to the invention for trimming glycoproteins. In another aspect, the invention relates to the process of production of the fusion enzyme. In a further aspect, the inventions concerns a process for trimming glycoproteins, comprising trimming the glycoprotein with a fusion enzyme according to the invention, to obtain a trimmed glycoprotein.

A pharmaceutical composition is described. The chemically stable pharmaceutical composition comprises (i) a drug component consisting of mometasone, mometasone furoate, or a combination thereof, (ii) a propellant component comprising 1,1-difluoroethane (R-152a), and (iii) ethanol in an amount of from 0.5 to 10% by weight based on the total weight of the chemically stable pharmaceutical composition. The drug component comprises from 0.01 to 1.0 weight % of the total weight of the chemically stable pharmaceutical composition. At least 95 weight % of the propellant component is 1,1-difluoroethane (R-152a). The drug component is the sole drug component in the pharmaceutical composition. The chemically stable pharmaceutical composition is surfactant-free.

The invention provides bifunctional compounds of formula (I) or a pharmaceutically acceptable salt thereof. Formula (I). The compounds cause the degradation of SMARCA2 via the targeted ubiquination of SMARCA2 protein and subsequent proteasomal degradation and are thus useful for the treatment of cancer. The targeting ligand is of formula (TL).

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Disclosed are Hematopoietic Progenitor Kinase 1 (HPK1) degradation/disruption compounds including a HPK1 ligand, a degradation/disruption tag and a linker, and methods for use of such compounds in the treatment of HPK1-mediated diseases.