The present disclosure relates to improvements in the selection and formulation of PBAE polymers using a design of experiment approach, in which statistical methods are used to limit possible experimental conditions. The present disclosure relates to improved PBAE polymers and formulations.

A composition includes a macromolecular polyacrylamide copolymer excipient with an α-end including a ROMP-active norbornene end-group and a ω-end including a terminal monomer with and end group chosen from: a hydrogen atom (H); or a functionalized acrylate with functionality chosen from alkyl, hydroxyl (OH), methyl-polyethylene glycol ((PEG)-CH.sub.3), hydroxy-PEG (PEG-OH), carboxylic acid (COOH), and combinations thereof. A biological compound chosen from active pharmaceutical ingredients, proteins, polynucleotides, and mixtures and combinations thereof is non-covalently bound with the macromolecular excipient.

A composition includes a macromolecular polyacrylamide copolymer excipient with an α-end including a ROMP-active norbornene end-group and a ω-end including a terminal monomer with and end group chosen from: a hydrogen atom (H); or a functionalized acrylate with functionality chosen from alkyl, hydroxyl (OH), methyl-polyethylene glycol ((PEG)-CH.sub.3), hydroxy-PEG (PEG-OH), carboxylic acid (COOH), and combinations thereof. A biological compound chosen from active pharmaceutical ingredients, proteins, polynucleotides, and mixtures and combinations thereof is non-covalently bound with the macromolecular excipient.

At least one nanoworm comprises a plurality of alkene units and a plurality of macroCTA polymer units. The macroCTA polymer units include R.sup.1 groups from reversible addition-fragmentation chain-transfer agents. In certain aspects, the R.sup.1 groups of the macroCTA polymer units are functional groups, such as a carboxylic acid, an alkyne, a pyridine, a dopamine, a thiolactone, a biotin, an azide, a peptide sequence, a sugar sequence, a protease, a glycanase, a polymer, other functional groups, and combinations thereof. In certain aspects, the macroCTA polymer units comprise quaternized amines, In certain aspects, the macroCTA polymer units comprise functionalized quaternized amines, such as an alkyl group, a carboxylic acid, an alkyne, a pyridine, a dopamine, a thiolactone, a biotin, an azide, a peptide sequence, a sugar sequence, a protease, a glycanase, a polymer, other functional groups, and combinations thereof. In certain aspects, the coating comprises the at least one nanoworm.

The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F.sup.1).sub.x—P in the presence of a catalyst, wherein S(F.sup.1).sub.x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q.sup.1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F.sup.1).sub.x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q.sup.1 capable of reacting with functional group F.sup.1 and a target molecule D connected to Q.sup.1 via a linker L.sup.2 to obtain the antibody-conjugate wherein linker L comprises S—Z.sup.3-L.sup.2 and wherein Z.sup.3 is a connecting group resulting from the reaction between Q.sup.1 and F.sup.1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.

The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F.sup.1).sub.x—P in the presence of a catalyst, wherein S(F.sup.1).sub.x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q.sup.1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F.sup.1).sub.x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q.sup.1 capable of reacting with functional group F.sup.1 and a target molecule D connected to Q.sup.1 via a linker L.sup.2 to obtain the antibody-conjugate wherein linker L comprises S—Z.sup.3-L.sup.2 and wherein Z.sup.3 is a connecting group resulting from the reaction between Q.sup.1 and F.sup.1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.

Compositions and methods for treating cancer that include administering a therapeutically effective amount of a tumor suppressor mRNA complexed with a delivery vehicle as described herein, e.g., a nanoparticle.

Provided herein are methods and related compositions for administering viral transfer vectors and antigen-presenting cell targeted immunosuppressants.

Provided herein are multi-functional particles. The particles may include poly(lactide-co-glycolide)-g-polyethylenimine (PLGA-g-PEI (PgP)), at least one targeting moiety, at least one therapeutic agent, and/or at least one nucleic acid. Also provided herein are methods of using the multi-functional particles.

A hyperbranched polymer includes a hyperbranched, hydrophobic molecular core, respective low molecular weight polyethyleneimine chains attached to at least three branches of the hyperbranched, hydrophobic molecular core, and respective polyethylene glycol chains attached to at least two other branches of the hyperbranched, hydrophobic molecular core. Examples of the hyperbranched polymer may be used to form hyperbranched polyplexes, and may be included in DNA or RNA delivery systems.