The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the programmed cell death 1 ligand 1 (PD-L1) gene, and methods of using such RNAi agents to inhibit expression of a PD-L1 gene and methods of treating subjects having a PD-L1-associated disorder.

A physically stable compositions in the form of an injectable aqueous solution, the pH of which is from 6.0 to 8.0, including at least: a basal insulin of which the isoelectric point (pI) is from 5.8 to 8.5, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical.

A physically stable compositions in the form of an injectable aqueous solution, the pH of which is from 6.0 to 8.0, including at least: a basal insulin of which the isoelectric point (pI) is from 5.8 to 8.5, and a co-polyamino acid bearing carboxylate charges and at least one hydrophobic radical.

An antibody includes a polyamidoamine (PAMAM) dendrimer and a first functional group. The polyamidoamine (PAMAM) dendrimer includes a plurality of branches and each of the branches has a phenylboronic acid (PBA) terminal group. The first functional group is bonded to at least one of the PBA terminal groups.

An antibody includes a polyamidoamine (PAMAM) dendrimer and a first functional group. The polyamidoamine (PAMAM) dendrimer includes a plurality of branches and each of the branches has a phenylboronic acid (PBA) terminal group. The first functional group is bonded to at least one of the PBA terminal groups.

The present invention provides a modified RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand targets an HBV mRNA; all of the nucleotide sugars of the RNAi agent are 2′-modified; and at least one of the sense and antisense strands is conjugated to at least one targeting ligand that comprises two or more building blocks connected to a biantennary or triantennary branched linker, optionally via one or more linking groups.

This invention generally relates to the field of phosphoramidite derivatives. In particular, the invention relates to N-Acetylgalactosamine phosphoramidite molecules and to conjugates of nucleic acid molecules with N-Acetylgalactosamine containing molecules. Also provided are methods for preparation of these molecules and possible uses thereof, in particular in medicine.

Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5′ end to 3′ end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

Provided is a drug containing a liver targeting specific ligand and a thyroid hormone receptor agonist in its structure, which is a new drug structure formed by linking the liver targeting specific ligand with the thyroid hormone receptor agonist through a branched chain, a linker and a linking chain. Thyroid hormone receptors (TRs) are divided into two subtypes, TR-α and TR-β, wherein, TR-β is mainly expressed in liver, and TR-α is mainly expressed in heart, nervous system, etc. In certain embodiments, it is envisaged that the provided drug has the action of liver targeting, can specifically bring the thyroid hormone receptor agonist into liver, without entering heart and other issues, and may thereby avoid side effects caused by the action of the thyroid hormone receptor agonist on other issues, and maintain its therapeutic efficacy in the treatment of lipid metabolism disorders and related complications.

The invention relates to novel conjugating reagents capable of reaction with at least one nucleophile present in a peptide or protein, which contain at least one leaving group which is lost on reaction with said nucleophile, in which the leaving group includes a portion —(CH.sub.2CH.sub.2O).sub.n—, in which n is a number of six or more; and novel processes for the preparation of conjugates containing peptides or proteins made using such reagents.