Coronavirus vaccine

Patent No. US11471525 (titled "Coronavirus vaccine") on Dec 9, 2021. The application was issued on Oct 18, 2022.

'525 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 and treatments against SARS-CoV-2, given its high transmissibility and potential for severe illness, especially in vulnerable populations. Nucleic acid-based vaccines, such as RNA vaccines, offer a promising approach due to their rapid development and scalable production.

The underlying idea behind '525 is to use a genetically engineered nucleic acid, specifically messenger RNA (mRNA), to deliver instructions to human cells to produce an antigenic protein derived from SARS-CoV-2. This protein, when expressed by the body's cells, triggers an immune response, leading to the production of antibodies and T cells that can protect against future infection. A key aspect is the use of a pre-fusion stabilized spike protein, modified to elicit a more effective immune response.

The claims of '525 focus on a method of stimulating an immune response by administering a composition containing mRNA. This mRNA encodes a pre-fusion stabilized SARS-CoV-2 spike protein with specific mutations (K986P and V987P) and a D614G substitution. The mRNA also includes heterologous untranslated regions (UTRs) and a terminal poly(A) sequence. The mRNA is delivered via lipid nanoparticles (LNPs) composed of a cationic lipid, DSPC, cholesterol, and a PEG-lipid in a defined molar ratio, administered intramuscularly.

In practice, the invention involves synthesizing mRNA encoding a modified spike protein, encapsulating it within LNPs for efficient delivery and protection, and injecting this composition into a subject. The mRNA then directs the subject's cells to produce the spike protein, which, due to its pre-fusion stabilized conformation, presents a more effective target for the immune system. This results in a robust and targeted immune response against SARS-CoV-2.

The invention differentiates itself from prior approaches by focusing on a specific combination of mRNA design elements and delivery mechanisms. The use of a pre-fusion stabilized spike protein, specific UTRs, and LNPs with a defined lipid composition are all intended to improve the immunogenicity and efficacy of the vaccine. The claim language suggests a focus on achieving a strong and protective immune response with a specific formulation and administration route.

How does this patent fit in bigger picture?

Technical Landscape

In the early 2020s when ’525 was filed, the global medical community was urgently seeking rapid-response vaccine platforms to address emerging viral pathogens at a time when vaccine development was typically implemented using inactivated viruses or recombinant protein subunits. While nucleic acid-based technologies were recognized as promising for scalable production, systems commonly relied on DNA or modified mRNA rather than unmodified RNA sequences due to concerns regarding stability and immunogenicity. During this era, engineering mRNA to induce potent humoral and cellular immune responses without extensive chemical modifications was non-trivial, as hardware and software constraints made the optimization of non-coding regulatory elements and lipid nanoparticle delivery systems essential for achieving therapeutic efficacy.

Prosecution Position

The examiner allowed the application based on the specific combination of mutations within the SARS-CoV-2 spike protein and the use of particular non-coding regulatory regions surrounding the mRNA coding sequence. Specifically, the examiner noted that the inclusion of a terminal poly(A) sequence and the discovery that certain combinations of untranslated regions (UTRs) could be optimized to boost the mRNA's ability to trigger an immune response—even when the mRNA did not contain chemical modifications—distinguished the invention from existing technology.

Claims

This patent contains 34 claims, with independent claims numbered 1, 15, and 25. The independent claims generally focus on methods of stimulating an immune response in a subject by administering a composition comprising mRNA encoding a SARS-CoV-2 spike protein complexed with lipid nanoparticles. The dependent claims generally elaborate on specific features of the mRNA, lipid nanoparticles, and administration methods.

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, Claim 25)	In a particularly preferred embodiment, the at least one nucleic acid (e.g. DNA or RNA) of the composition is complexed with one or more lipids thereby forming LNPs, 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. 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, used in the lipid nanoparticle formulation.
D614G amino acid substitution (Claim 1, Claim 25)	Each spike protein provided herein and contemplated as suitable antigen in the context of the invention may have one or more of the following amino acid variations (amino acid positions according to reference SEQ ID NO: 1): D614G or G614D	A specific amino acid substitution at position 614 (aspartic acid replaced with glycine) in the spike protein sequence.
Polyethylene glycol (peg)-lipid according to formula IVa (Claim 1, Claim 25)	In a 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 LNPs, 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 PEGylated lipid with a specific chemical structure (defined by formula IVa in the patent) used in the lipid nanoparticle formulation to provide steric stabilization.
Pre-fusion stabilized spike protein (Claim 1, Claim 25)	In particularly preferred embodiments, 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. Furthermore, remaining of the protein in the pre-fusion conformation is aimed to avoid immunopathological effects, like e.g. enhanced disease and/or antibody dependent enhancement (ADE).	A spike protein (S) that has been modified to favor the pre-fusion conformation, typically by amino acid substitutions that increase the protein's stability in that conformation. This conformation is desirable for eliciting neutralizing antibodies and avoiding immunopathological effects.
Pre-fusion stabilizing K986P and V987P mutation (Claim 1, Claim 25)	Stabilization of the SARS-CoV-2 coronavirus spike protein may be obtained by substituting at least one amino acid at position K986 and/or V987 with amino acids that stabilize the spike protein in a perfusion conformation (amino acid positions according to reference SEQ ID NO: 1). Preferably, stabilization of the perfusion conformation is obtained by introducing two consecutive proline substitutions at residues K986 and V987 in the spike protein (Amino acid positions according to reference SEQ ID NO: 1).	Specific amino acid substitutions at positions K986 and V987 (replaced with proline) in the spike protein sequence that promote and stabilize the pre-fusion conformation.

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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US11471525

Application Number: US17546414A
Filing Date: Dec 9, 2021
Publication Date: Oct 18, 2022
External Links: Slate, USPTO, Google Patents

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