A method is provided to conveniently separate racemic (3R,4S)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide and (3S,4R)-3-acetamido-4-allyl-N-(tert-butyl)pyrrolidine-3-carboxamide using selective crystallization with chiral carboxylic acids.

The invention generally relates to an improved process for the preparation of N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide,

##STR00001## as well as novel intermediates employed in the process, which may be useful for the treatment of cancer.

In some embodiments, the present disclosure provides amino acid compounds that are useful for producing products such as peptides. In some embodiments, the present disclosure provides peptides comprising residues of provided amino acids.

In some embodiments, the present disclosure provides amino acid compounds that are useful for producing products such as peptides. In some embodiments, the present disclosure provides peptides comprising residues of provided amino acids.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

Disclosed are cationic lipids which are compounds of Formula (I), (II), (III), (IV), (V), or (VI). Cationic lipids 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.

##STR00001##

Disclosed are cationic lipids which are compounds of Formula (I), (II), (III), (IV), (V), or (VI). Cationic lipids 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.

##STR00001##

Novel lipids, compositions, and methods of using the novel lipids and compositions are disclosed. Three-component lipid nanoparticle compositions comprising the novel lipids or other types of lipids, and methods of using the three-component lipid nanoparticle compositions are disclosed. Three-component lipid nanoparticle compositions contain a steroidal or structural lipid-containing component, a PEGylated lipid-containing component, a cationic or ionizable lipid-containing component, and are free of phospholipids. Pharmaceutical formulations including the three-component lipid nanoparticle compositions and further including therapeutic and/or prophylactics such as mRNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs.

Novel lipids, compositions, and methods of using the novel lipids and compositions are disclosed. Three-component lipid nanoparticle compositions comprising the novel lipids or other types of lipids, and methods of using the three-component lipid nanoparticle compositions are disclosed. Three-component lipid nanoparticle compositions contain a steroidal or structural lipid-containing component, a PEGylated lipid-containing component, a cationic or ionizable lipid-containing component, and are free of phospholipids. Pharmaceutical formulations including the three-component lipid nanoparticle compositions and further including therapeutic and/or prophylactics such as mRNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs.