The present invention relates to compositions and methods for inducing an adaptive immune response in a subject. In certain embodiments, the present invention provides a composition comprising a nucleoside-modified nucleic acid molecule encoding an antigen, adjuvant, or a combination thereof. For example, in certain embodiments, the composition comprises a vaccine comprising a nucleoside-modified nucleic acid molecule encoding an antigen, adjuvant, or a combination thereof.

A novel multi-arm polyethylene glycol (PEG) (I) and preparation method thereof. Active derivatives (II) based on the multi-arm PEG. Gels formed of the active derivatives. Drug conjugates formed of the active derivatives and drug molecules and uses thereof in medical preparation. The multi-arm PEG is formed by polymerizing ethylene oxide with pentaerythritol oligomers as initiator, wherein PEG is the same or different and is a —(CH2CH2O)m-, the average value of m is an integer of 3-1000, l is an integer more than or equal to 2. An 8-arm PEG is preferred, wherein l is equal to 3. The active derivatives (II) comprise link groups X attached to PEG and active end groups F attached to X.

The instant disclosure provides (among other things) improved methods of preparing fluorenyl-based polymeric reagents, methods of recovering and purifying such polymeric reagents, methods of reducing unwanted impurities in a fluorenyl-based polymeric reagent, fluorenyl-based polymeric reagents prepared by the methods described herein, and conjugates prepared by reaction with fluorenyl-based polymeric reagents prepared by the methods described herein.

A multi-branched drug conjugate of formula (I) or a pharmaceutically acceptable salt thereof. In the formula, R is an organic center, POLY is a polymer, L is a multivalent linker, T is a targeting molecule, D is an active agent, and q is any integer between 3 and 8. The symbol “*” in L represents a junction point of the multivalent linker L and the targeting molecule T, “#” represents a junction point of the multivalent linker L and the active agent D, and “%” represents a junction point of the multivalent linker L and POLY. 1 is any integer between 2 and 20, and m and n are each an integer between 0 and 10. T is iRGD, cRGD, tLyp-1, Lyp-1, RPARPAR, Angiopep2, or GE11. D is a camptothecin drug. ##STR00001##

The present disclosure provides conjugates comprising a Factor VIII moiety covalently attached via an oxime-containing linkage to a water-soluble polymer, such as for example, a polyethylene glycol polymer. Methods for preparing and for administering such conjugates, are also provided, as are water-soluble polymer oxyamine reagents useful for preparing the subject conjugates, among other things.

A compound of formula (I) having the structure shown below:

##STR00001##

wherein R.sup.B, R.sup.F1, R.sup.A1, X.sup.a and X.sup.b are as defined herein.

Disclosed in the present invention is a method for preparing a Y-branched hydrophilic polymer carboxylic acid derivative, in particular a method for preparing a Y-branched polyethylene glycol carboxylic acid derivative having a high purity and high molecular weight. The preparation steps are simple, the product of the reaction is easy to be separated, the cost for separation is low, and the purity and yield of the product are high, facilitating the subsequent preparation of other derivatives and medicament conjugates based on the preparation of the carboxylic acid derivative, which is advantageous for industrial scale-up and commercial applications. The prepared Y-branched hydrophilic polymer carboxylic acid derivative (in particular the Y-branched polyethylene glycol carboxylic acid derivative having a high molecular weight) product has a high purity and high commercial application value, in particular in the use of the preparation of medicaments for preventing and/or treating diseases.

A fluoropolyether group-containing compound of formula (1a) or formula (1b):

##STR00001##

wherein R.sup.F1, R.sup.F2, R.sup.1 and R.sup.2 are as defined herein.

The subject disclosure is directed to functionalized bile acids, preparation thereof, and usage thereof for therapeutic and material applications. In one embodiment, a method of generating functionalized bile acid materials can comprise directly activating a carboxylic acid of a bile acid compound using a coupling agent comprising an amide or ester compound, thereby generating an intermediate bile acid derivative material. The method can further comprise attaching a functional group material to the intermediate bile acid derivative material by reacting the functional group material and the intermediate bile acid derivative material, thereby generating a functionalized bile acid material.

The invention provides for novel thermo-responsive polymers and compositions comprising the same. In some embodiments, the polymers are water soluble, pH-degradable and have tunable lower critical solution temperatures. Other aspects of the invention include micelles and gels comprising the thermo-responsive polymers and derivatives thereof, as well as methods of delivering therapeutic agents comprising administering a biodegradable gel or micelle comprising a polyacetal compound cross-linked with a linker.