This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

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.

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.

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.

Disclosed are hydrogel compositions that can be used to deliver therapeutic agents, including therapeutic proteins, to patients in need thereof. In an embodiment, the therapeutic agent is an immune checkpoint blockade antibody, and the hydrogel is a thermoresponsive polymer crosslinked with a hydrophilic polymer.

The invention relates to a method for attenuating vibrations and/or shocks, said method comprising providing a damper assembly which comprises a moving part and a supramolecular polymer in contact with said moving part, and exposing said moving part to said vibrations and/or shocks, wherein said supramolecular polymer is obtained by reacting: at least one first polymer [polymer (P1)] comprising a polymer chain [chain (R)] consisting of a plurality of non-ionisable recurring units [units (U)], said polymer (P1) having two chain ends (E1, E1′), each end comprising at least one ionisable acid group, and at least one second polymer [polymer (P2)] comprising a polymer chain [chain (R)] consisting of a plurality of recurring units [units (U)], said chain (R) being equal to or different from that of polymer (P1), and said polymer (P2) having two chain ends (E2, E2′), each end comprising at least one ionisable amino group.

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 polymer includes the reaction product of A, B, and C, and optionally D, wherein: A is a polyepoxide that is: the condensation product of phenol, formaldehyde, and epichlorohydrin; the condensation product of bisphenol A, formaldehyde, and epichlorohydrin; or a combination of said condensation products; B is at least one polyoxyalkylene with a terminal primary amine group wherein each polyoxyalkylene comprises an ethyleneoxy moiety and a propyleneoxy moiety and independently has the following structure: ##STR00001## wherein R is a hydrogen atom or a C.sub.1-C.sub.4 group, and wherein each of x and y is independently from 0 to about 500 and x+y>0; and C is an anchoring compound that is: a secondary amine; a monocarboxylic acid; a cyclic imide; or a combination thereof, and D is an alkylating agent. This polymer is included in a composition that further includes a compound such as a particulate solid.

The present invention relates to the use of at least one tetra functional non-ionic amphiphilic block copolymer as a vehicle for capped or uncapped mRNA for intracellular delivery for gene therapy.

The compounds disclosed herein (e.g., compounds of Formula (I), (II), (III), and (IV)) comprise a lipid substructure comprising a hydrophobic moiety and a hydrophilic moiety; and two or more polymeric groups (e.g., two or more polyethylene glycol (PEG) groups). The compounds provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

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