Coronavirus vaccine

Patent No. US11576966 (titled "Coronavirus vaccine") on Nov 15, 2021. The application was issued on Feb 14, 2023.

'966 is related to the field of nucleic acid-based vaccines, specifically those designed to combat coronavirus infections, particularly SARS-CoV-2. The background acknowledges the urgent need for effective treatments and prophylaxis against SARS-CoV-2, given the global pandemic and the limitations of existing supportive care. Nucleic acid vaccination, using DNA or RNA, is presented as a promising approach due to its rapid development time and potential for inducing protective immunological responses, including both humoral and cellular immunity.

The underlying idea behind '966 is to utilize a genetically engineered nucleic acid, specifically mRNA, to deliver the instructions for producing a SARS-CoV-2 antigen within the patient's own cells. This antigen, ideally a stabilized version of the Spike protein, then triggers the body's immune system to develop protective antibodies and T-cell responses. The key insight is that by optimizing the mRNA sequence and delivery, a strong and durable immune response can be achieved, offering protection against the virus.

The claims of '966 focus on a composition containing mRNA that encodes a SARS-CoV-2 Spike protein with specific stabilizing mutations (K986P and V987P) and amino acid substitutions (H69del, V70del, S477N, T478K, E484A, N501Y, and D614G or K417N, S477N, T478K, E484A, D614G, N501Y, P681H, H655Y and Q493R). This mRNA is complexed with lipid nanoparticles (LNPs) composed of a cationic lipid, a neutral lipid, a sterol, and a PEG-lipid in a defined molar ratio. The composition also includes a pharmaceutically acceptable carrier.

In practice, the mRNA within the LNP is delivered to cells, where it is translated into the stabilized Spike protein. The specific mutations and substitutions in the Spike protein are designed to enhance its stability in the prefusion conformation, which is believed to be more effective at eliciting neutralizing antibodies. The LNP protects the mRNA from degradation and facilitates its entry into cells. The resulting immune response includes both antibody production and T-cell activation, providing a comprehensive defense against SARS-CoV-2.

This approach differs from prior solutions by focusing on a specifically engineered mRNA sequence encoding a stabilized Spike protein delivered via LNPs. Traditional vaccines often use inactivated viruses or protein subunits, which may be less effective at inducing a broad immune response or may require adjuvants to enhance their immunogenicity. The mRNA-based approach offers the potential for rapid development and adaptation to emerging viral variants, as well as the ability to elicit both humoral and cellular immunity without the need for live viruses or complex protein production processes.

How does this patent fit in bigger picture?

Technical Landscape

In the early 2020s when ’966 was filed, the global medical community was facing an urgent need for rapid vaccine development at a time when traditional vaccine platforms typically relied on live-attenuated or inactivated viruses which required long development timelines. While nucleic acid-based technologies were emerging, systems commonly relied on supportive symptomatic care rather than targeted genomic prophylaxis for novel respiratory pathogens. During this era, hardware and software constraints in bioinformatics made the rapid identification and stabilization of viral antigens non-trivial, particularly when attempting to maintain proteins in specific structural conformations to ensure a potent immune response.

Prosecution Position

The examiner allowed the application because the prior art did not describe or suggest a specific mRNA sequence that encodes a SARS-CoV-2 spike protein with a high degree of similarity to the sequence identified as SEQ ID NO: 10. Specifically, the approved claims involve a unique combination of several distinct genetic mutations (K986P, V987P, H69del, V70del, S477N, T478K, E484A, N501Y, and D614G) integrated with lipid nanoparticle delivery components and specific non-translated regulatory regions. The examiner concluded that the existing technical records did not teach this precise genetic blueprint for the spike protein in conjunction with the recited mutations.

Claims

Key Claim Terms New

Definitions of key terms used in the patent claims.

Term (Source)	Support for Specification	Interpretation
Heterologous untranslated region (Claim 1, Claim 26)	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 region of a nucleic acid molecule that is not translated into a protein and is derived from a different gene, allele, species, or virus than the coding sequence it is associated with.
K986p and V987p stabilizing mutations (Claim 1, Claim 26)	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 K986 and V987 in the spike protein sequence that stabilize the protein in its prefusion conformation.
Lipid nanoparticles (Claim 1, Claim 26)	In preferred embodiments of the second aspect, the at least one nucleic acid (e.g. DNA or RNA), preferably the at least one RNA, and optionally the at least one further nucleic acid, is complexed, encapsulated, partially encapsulated, or associated with one or more lipids (e.g. cationic lipids and/or neutral lipids), thereby forming lipid-based carriers such as liposomes, lipid nanoparticles (LNPs), lipoplexes, and/or nanoliposomes. The term “lipid nanoparticle”, also referred to as “LNP”, is not restricted to any particular morphology, and include any morphology generated when a cationic lipid and optionally one or more further lipids are combined, e.g. in an aqueous environment and/or in the presence of a nucleic acid, e.g. an RNA.	Microscopic vesicles formed by lipids, including cationic lipids, neutral lipids, steroids, and polymer-conjugated lipids, used to encapsulate or associate with nucleic acids.
Pharmaceutically acceptable carrier (Claim 1, Claim 26)	The term “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” as used herein preferably includes the liquid or non-liquid basis of the composition for administration. If the composition is provided in liquid form, the carrier may be water, e.g. pyrogen-free water; isotonic saline or buffered (aqueous) solutions, e.g. phosphate, citrate etc. buffered solutions.	A substance suitable for administration to a subject that does not substantially reduce the biological activity or pharmaceutical effectiveness of the composition.
Pre-fusion stabilized spike protein (Claim 1, Claim 26)	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) that has been modified to retain its prefusion conformation, typically by introducing specific amino acid substitutions.

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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US11576966

Application Number: US17526912A
Filing Date: Nov 15, 2021
Publication Date: Feb 14, 2023
External Links: Slate, USPTO, Google Patents

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