Coronavirus vaccine

Patent No. US11241493 (titled "Coronavirus vaccine") on Apr 15, 2021. The application was issued on Feb 8, 2022.

'493 is related to the field of vaccines, specifically those designed to prevent or treat infections caused by coronaviruses, particularly SARS-CoV-2, the virus responsible for COVID-19. The background of the invention lies in the urgent need for effective vaccines against SARS-CoV-2, given its high transmissibility and potential for severe disease, especially in vulnerable populations. Existing approaches, such as protein-based or live attenuated vaccines, may have limitations in terms of production speed, cost, and storage requirements, motivating the development of nucleic acid-based vaccines.

The underlying idea behind '493 is to utilize messenger RNA (mRNA) to deliver genetic instructions to cells, prompting them to produce a stabilized form of the SARS-CoV-2 spike protein. This stabilized protein, achieved through specific mutations (K986P and V987P), is designed to elicit a strong and protective immune response against the virus. The mRNA is formulated with lipid nanoparticles (LNPs) to facilitate its delivery into cells and enhance its stability.

The claims of '493 focus on a specific mRNA composition for a SARS-CoV-2 vaccine. This composition includes an mRNA sequence encoding a pre-fusion stabilized spike protein with particular mutations, heterologous untranslated regions (UTRs) to enhance expression, and a lipid nanoparticle (LNP) delivery system. The LNP is defined by its specific lipid components, including a cationic lipid (formula III-3), a neutral lipid (DSPC), cholesterol, and a PEG-lipid (formula IVa), all present in a defined molar ratio.

In practice, the invention involves synthesizing an mRNA sequence that encodes the stabilized spike protein, incorporating optimized UTRs to improve its expression, and then encapsulating this mRNA within LNPs. The LNPs protect the mRNA from degradation and facilitate its entry into cells upon injection. Once inside the cells, the mRNA is translated into the stabilized spike protein, which then triggers an immune response, leading to the production of neutralizing antibodies and T cells that can protect against SARS-CoV-2 infection.

This approach differentiates itself from prior solutions by focusing on a stabilized spike protein delivered via a precisely formulated LNP. The stabilization mutations are intended to present the spike protein in its most immunogenic conformation, while the specific lipid composition of the LNP is designed to optimize delivery and minimize adverse reactions. The use of mRNA allows for rapid vaccine development and production, offering a flexible platform that can be adapted to address emerging viral variants.

How does this patent fit in bigger picture?

Technical Landscape

In the early 2020s when ’493 was filed, the development of rapid-response medical countermeasures was critical at a time when vaccine platforms typically relied on inactivated viruses or recombinant proteins rather than synthetic nucleic acids. While mRNA technology was an established area of research, systems commonly relied on complex cold-chain logistics and traditional delivery methods, and engineering stable, pre-fusion viral antigens encapsulated in specific lipid delivery vehicles made the creation of highly effective, scalable vaccines non-trivial.

Prosecution Position

The examiner allowed the application because the prior art does not describe or suggest a specific vaccine composition combining several distinct elements: a messenger RNA encoding a SARS-CoV-2 spike protein with at least 95% similarity to a specific reference sequence (SEQ ID NO: 10) that includes two specific stabilizing mutations (K986P and V987P), at least one non-native regulatory region, and a delivery system using lipid nanoparticles. These nanoparticles must specifically include a cationic lipid known as ALC-0315, a neutral helper lipid, a steroid, and a PEG-modified lipid within defined percentage ranges.

Claims

This patent contains 29 claims, with independent claims 1, 1, and 1. The independent claims are directed to a composition comprising mRNA encoding a stabilized SARS-CoV-2 spike protein complexed with lipid nanoparticles. The dependent claims generally specify further details and limitations of the composition described in the independent claims, such as specific sequences, modifications, components, ratios, and characteristics of the mRNA and lipid nanoparticles.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)	Support for Specification	Interpretation
Cationic lipid according to formula III-3 (Claim 1)	In particularly preferred embodiments, the at least one nucleic acid (e.g. DNA or RNA) of the composition is complexed with one or more lipids thereby forming lipid nanoparticles (LNP), wherein the cationic lipid of the LNP is selected from structures III-1 to III-36 of Table 9 of published PCT patent application WO2018/078053A1. In particularly preferred embodiment of the second aspect, the at least one nucleic acid (e.g. DNA or RNA) of the composition is complexed with one or more lipids thereby forming lipid nanoparticles (LNP), wherein the LNP comprises a cationic lipid according to formula III-3: The lipid of formula III-3 as suitably used herein has the chemical term ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), also referred to as ALC-0315.	A specific cationic lipid with the chemical name ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), also referred to as ALC-0315. The structure is not explicitly shown in the specification, but is incorporated by reference to WO2018/078053A1.
Peg-lipid according to formula IVa (Claim 1)	In a particularly preferred embodiment, the at least one nucleic acid, preferably the at least one RNA is complexed with one or more lipids thereby forming lipid nanoparticles (LNP), wherein the LNP comprises a PEGylated lipid, wherein the PEG lipid is preferably derived from formula (IVa) of published PCT patent application WO2018/078053A1. Accordingly, PEGylated lipid derived from formula (IVa) of published PCT patent application WO2018/078053A1, and the respective disclosure relating thereto, is herewith incorporated by reference.	A polyethylene glycol-lipid (PEGylated lipid) with a specific chemical structure, where 'n' represents the number of ethylene glycol units and has a mean value ranging from 30 to 60. The structure is not explicitly shown in the specification, but is incorporated by reference to WO2018/078053A1.
Pre-fusion stabilized spike protein (Claim 1)	In a particularly preferred embodiment, the spike protein (S) that is provided by the nucleic acid of the first aspect is designed or adapted to stabilize the antigen in pre-fusion conformation. A pre-fusion conformation is particularly advantageous in the context of an efficient coronavirus vaccine, as several potential epitopes for neutralizing antibodies may merely be accessible in said pre-fusion protein conformation. In preferred embodiments, the pre-fusion stabilized spike protein (S_stab) comprises at least one pre-fusion stabilizing mutation, wherein the at least one pre-fusion stabilizing mutation comprises the following amino acid substitutions: K986P and V987P (amino acid positions according to reference SEQ ID NO: 1).	A spike protein that has been modified to favor the pre-fusion conformation. This modification includes a K986P and V987P mutation.
Pre-fusion stabilizing K986p and V987p mutation (Claim 1)	In a particularly preferred embodiment, the spike protein (S) that is provided by the nucleic acid of the first aspect is designed or adapted to stabilize the antigen in pre-fusion conformation. A pre-fusion conformation is particularly advantageous in the context of an efficient coronavirus vaccine, as several potential epitopes for neutralizing antibodies may merely be accessible in said pre-fusion protein conformation. In preferred embodiments, the pre-fusion stabilized spike protein (S_stab) comprises at least one pre-fusion stabilizing mutation, wherein the at least one pre-fusion stabilizing mutation comprises the following amino acid substitutions: K986P and V987P (amino acid positions according to reference SEQ ID NO: 1).	Specific amino acid substitutions at positions 986 and 987 of the spike protein, where lysine (K) is replaced with proline (P) at position 986, and valine (V) is replaced with proline (P) at position 987. These substitutions stabilize the spike protein in the pre-fusion conformation.
Sars-cov-2 spike protein (Claim 1)	In a particularly preferred embodiment, the spike protein (S) that is provided by the nucleic acid of the first aspect is designed or adapted to stabilize the antigen in pre-fusion conformation. A pre-fusion conformation is particularly advantageous in the context of an efficient coronavirus vaccine, as several potential epitopes for neutralizing antibodies may merely be accessible in said pre-fusion protein conformation. In preferred embodiments, the pre-fusion stabilized spike protein (S_stab) comprises at least one pre-fusion stabilizing mutation, wherein the at least one pre-fusion stabilizing mutation comprises the following amino acid substitutions: K986P and V987P (amino acid positions according to reference SEQ ID NO: 1).	A protein derived from the SARS-CoV-2 coronavirus that is at least 95% identical to SEQ ID NO: 10. This protein is modified to be pre-fusion stabilized, including a K986P and V987P mutation.

Litigation Cases New

US Latest litigation cases involving this patent.

Case Number	Filing Date	Title
2:23-cv-00610	Nov 13, 2023	Acuitas Therapeutics, Inc. V. Curevac Se

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US11241493

Application Number: US17231261A
Filing Date: Apr 15, 2021
Publication Date: Feb 8, 2022
External Links: Slate, USPTO, Google Patents

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