Abstract: A method for producing a homocyclic or heterocyclic compound includes reacting a compound of formula (I) with a compound of formula (II) in presence of a base: R1—B-G??(I) In formula (I), B is an unsaturated moiety selected from substituted or unsubstituted vinylene, ethynylene, aryleneethynylene, substituted or unsubstituted arylenevinylene, and a combination thereof, the vinylene or arylenevinylene has n (=0, 1 or 2) substituent(s) R2, G is an electron-withdrawing group, R1 is hydrogen or a substituent, and two of R1, R2 and G may joint together to form a ring. In formula (II), R3 and R4 are independently hydrogen or a substituent, R5 is an electron-withdrawing group, and two of R3, R4 and R5 may joint together to form a ring. The conjugate acid of the base has a pKa in the range of 1 to 15.

Abstract: Disclosed herein are methods of increasing the potency of nucleic acid loaded lipid nanoparticles (naLNPs) through certain novel and surprisingly superior LNP manufacturing techniques. Also disclosed are pharmaceutical compositions containing naLNPs manufactured according to the manufacturing methods described herein. The methods disclosed herein overcome major technical difficulties and high costs associated with previous LNP manufacturing techniques. The methods disclosed herein, therefore, greatly improve the industrial production of LNPs in unexpected ways thereby providing more potent naLNPs for nucleic acid delivery. Specifically, the invention disclosed herein are methods that show increased potency naLNPs due to increased mixing concentration of the lipids and mRNA during assembly.

Abstract: The invention encompasses novel ionizable lipids compounds and their use in lipid nanoparticles delivery systems that are useful in the delivery of nucleic acids to a mammalian subject that can be included for use, for example, as cancer vaccines, gene editing therapeutics, delivery of nucleic acid (e.g., mRNA) encoding antibodies, vaccines for infectious disease, and protein replacement therapeutics. Additionally, the invention encompasses compositions and therapeutics comprising the ionizable lipids in the lipid nanoparticles and the use of the composition and therapeutics for the preparation of a pharmaceutical composition, especially a vaccine, (e.g., for use in the prophylaxis or treatment of infectious diseases, tumor or cancer diseases, rare diseases, allergies, or autoimmune diseases). The invention encompasses methods of treatment or prophylaxis of the aforementioned diseases.

Abstract: A method for producing a homocyclic or heterocyclic compound includes reacting a compound of formula (I) with a compound of formula (II) in presence of a base: In formula (I), B is an unsaturated moiety selected from substituted or unsubstituted vinylene, ethynylene, aryleneethynylene, substituted or unsubstituted arylenevinylene, and a combination thereof, the vinylene or arylenevinylene has n (=0, 1 or 2) substituent(s) R2, G is an electron-withdrawing group, R1 is hydrogen or a substituent, and two of R1, R2 and G may joint together to form a ring. In formula (II), R3 and R4 are independently hydrogen or a substituent, R5 is an electron-withdrawing group, and two of R3, R4 and R5 may joint together to form a ring. The conjugate acid of the base has a pKa in the range of 1 to 15.

Abstract: A method for producing a homocyclic or heterocyclic compound includes reacting a compound of formula (I) with a compound of formula (II) in presence of a base: In formula (I), B is an unsaturated moiety selected from substituted or unsubstituted vinylene, ethynylene, aryleneethynylene, substituted or unsubstituted arylenevinylene, and a combination thereof, the vinylene or arylenevinylene has n (=0, 1 or 2) substituent(s) R2, G is an electron-withdrawing group, R1 is hydrogen or a substituent, and two of R1, R2 and G may joint together to form a ring. In formula (II), R3 and R4 are independently hydrogen or a substituent, R5 is an electron-withdrawing group, and two of R3, R4 and R5 may joint together to form a ring. The conjugate acid of the base has a pKa in the range of 1 to 15.

Abstract: A method for producing a homocyclic or heterocyclic compound includes reacting a compound of formula (I) with a compound of formula (II) in presence of a base: In formula (I), B is an unsaturated moiety selected from substituted or unsubstituted vinylene, ethynylene, aryleneethynylene, substituted or unsubstituted arylenevinylene, and a combination thereof, the vinylene or arylenevinylene has n (=0, 1 or 2) substituent(s) R2, G is an electron-withdrawing group, R1 is hydrogen or a substituent, and two of R1, R2 and G may joint together to form a ring. In formula (II), R3 and R4 are independently hydrogen or a substituent, R5 is an electron-withdrawing group, and two of R3, R4 and R5 may joint together to form a ring. The conjugate acid of the base has a pKa in the range of 1 to 15.