Coronavirus vaccine

Patent No. US11596686 (titled "Coronavirus vaccine") on Aug 9, 2022. The application was issued on Mar 7, 2023.

What is this patent about?

{'paragraph': '’686 is related to the field of nucleic acid vaccines, specifically those designed to prevent or treat coronavirus infections, particularly SARS-CoV-2 (the virus that causes COVID-19). The background acknowledges the urgent need for effective vaccines and treatments given the global pandemic and the limitations of existing approaches, such as protein-based vaccines, in terms of cost, production speed, and temperature stability. Nucleic acid-based vaccines offer a promising alternative due to their rapid development and scalable production.'}

{'paragraph': 'The underlying idea behind ’686 is to use a purified messenger RNA (mRNA) molecule to deliver the genetic instructions for a modified SARS-CoV-2 spike protein directly into cells. This mRNA is designed to be translated into a stable, pre-fusion version of the spike protein, which is a key target for neutralizing antibodies. By presenting the immune system with this specific form of the spike protein, the vaccine aims to elicit a strong and protective immune response against the virus.'}

{'paragraph': "The claims of ’686 focus on a specific mRNA construct comprising several key elements. It includes a 5' cap structure for efficient translation, a heterologous 5' untranslated region (UTR) and a heterologous 3' UTR to enhance stability and expression, and a coding sequence for a stabilized SARS-CoV-2 spike protein (S_stab) with specific mutations (K986P, V987P, and D614G). The mRNA may also contain nucleotide substitutions at one or more uracil positions, such as 1-methylpseudouridine or pseudouridine."}

{'paragraph': 'In practice, the mRNA is delivered to cells within the body, where it directs the synthesis of the modified spike protein. The pre-fusion stabilization is achieved through the K986P and V987P mutations, which lock the spike protein in a conformation that is more effective at eliciting neutralizing antibodies. The D614G substitution is included because it is a prevalent mutation in circulating SARS-CoV-2 strains. The heterologous UTRs are included to improve the stability and translation efficiency of the mRNA.'}

{'paragraph': "This approach differs from traditional vaccines that use inactivated viruses or protein subunits. By delivering the genetic instructions directly, the body's own cells become the antigen factories, potentially leading to a more robust and durable immune response. The use of lipid nanoparticles (LNPs) to encapsulate the mRNA further enhances its delivery and protects it from degradation before it can reach the target cells."}

How does this patent fit in bigger picture?

Technical Landscape

In the early 2020s when ’686 was filed, the technical landscape was defined by an urgent global requirement for rapid vaccine development at a time when traditional vaccine platforms commonly relied on inactivated viruses or recombinant proteins rather than synthetic nucleic acid sequences. While mRNA technology had been explored for years, systems typically implemented lipid nanoparticle (LNP) delivery mechanisms to overcome the inherent instability of RNA and ensure efficient intracellular delivery. Engineering constraints at this time made the stabilization of viral antigens in their pre-fusion conformation non-trivial, requiring specific amino acid substitutions to maintain structural integrity and enhance immunogenicity.

Prosecution Position

Following the filing of this document, the examiner issued a non-final Office Action rejecting the pending claims. The prosecution record indicates that claims 1-8 and 11-30 were rejected primarily on the grounds of non-statutory double patenting over an issued patent and several copending applications. The examiner also noted prior art disclosures regarding LNP delivery of mRNA and specific SARS-CoV-2 spike protein sequences, though it was observed that the prior art did not teach the specific combination of mutations claimed. The application later proceeded to allowance, but the provided record does not describe the specific technical reasoning or claim changes that led to that outcome.

Claims

This patent contains 30 claims, with independent claims 1 and 26 directed to a purified mRNA encoding a stabilized SARS-CoV-2 spike protein and a composition containing the mRNA, respectively. The dependent claims generally elaborate on specific features and variations of the mRNA and the composition, such as the UTR sequence, cap structure, amino acid substitutions in the spike protein, lipid nanoparticle composition, and methods of use.

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)Support for SpecificationInterpretation
D614g amino acid substitution
(Claim 1)
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 G614DA specific amino acid substitution at position 614 in the spike protein sequence, where Aspartic acid (D) is replaced by Glycine (G).
Heterologous 3' Utr
(Claim 26)
The term “3′-untranslated region” or “3′-UTR” or “3′-UTR element” will be recognized and understood by the person of ordinary skill in the art, and are e.g. intended to refer to a part of a nucleic acid molecule located 3′ (i.e. downstream) of a coding sequence and which is not translated into protein. A 3′-UTR may be part of a nucleic acid, e.g. a DNA or an RNA, located between a coding sequence and an (optional) terminal poly(A) sequence. A 3′-UTR may comprise elements for controlling gene expression, also called regulatory elements.A nucleotide sequence located downstream of the coding sequence in the mRNA that is not translated into protein and is derived from a different gene, allele, species, or virus than the coding sequence.
Heterologous 5' untranslated region
(Claim 1)
The term “untranslated region” or “UTR” or “UTR element” will be recognized and understood by the person of ordinary skill in the art, and are e.g. intended to refer to a part of a nucleic acid molecule typically located 5′ or 3′ located of a coding sequence. An UTR is not translated into protein. An UTR may be part of a nucleic acid, e.g. a DNA or an RNA. An UTR may comprise elements for controlling gene expression, also called regulatory elements.A nucleotide sequence located upstream of the coding sequence in the mRNA that is not translated into protein and is derived from a different gene, allele, species, or virus than the coding sequence.
K986p and V987p stabilizing substitutions
(Claim 1)
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). In preferred embodiments, the pre-fusion stabilizing mutation comprises an amino acid substitution at position K986 and V987, wherein the amino acids K986 and/or V987 are substituted with one selected from A, I, L, M, F, V, G, or P (amino acid positions according to reference SEQ ID NO: 1).Specific amino acid substitutions at positions 986 (Lysine to Proline) and 987 (Valine to Proline) in the spike protein sequence, which promote and stabilize the pre-fusion conformation of the protein.
Pre-fusion stabilized spike protein
(Claim 1)
The term “pre-fusion conformation” as used herein relates to a structural conformation adopted by the ectodomain of the coronavirus S protein following processing into a mature coronavirus S protein in the secretory system, and prior to triggering of the fusogenic event that leads to transition of coronavirus S to the postfusion conformation. A “pre-fusion stabilized spike protein (S_stab)” as described herein comprises one or more amino acid substitutions, deletions, or insertions compared to a native coronavirus S sequence that provide for increased retention of the prefusion conformation compared to coronavirus S ectodomain trimers formed from a corresponding native coronavirus S sequence.A spike protein (S) derived from SARS-CoV-2 that is modified to favor the pre-fusion conformation, typically by amino acid substitutions such as K986P and V987P.

Litigation Cases New

US Latest litigation cases involving this patent.

Case NumberFiling DateTitle
2:23-cv-00610Nov 13, 2023Acuitas Therapeutics, Inc. V. Curevac Se

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US11596686

Application Number
US17818699A
Filing Date
Aug 9, 2022
Publication Date
Mar 7, 2023
External Links
Slate, USPTO, Google Patents