Technology, that is what. I saw an article describing the contents of the Pfizer-BioNTech COVID-19 vaccine and thought it would be fun to break down the Moderna vaccine components as well as looking into their IP (and potentially conflicting IP). This post focuses on the contents of the Moderna COVID-19 vaccine. A follow-up post will investigate both Moderna’s IP as well as the potentially conflicting IP I discussed a few months ago.
The Moderna COVID-19 vaccine is given as a 0.5 mL intramuscular injection, with 2 doses, 1 month apart being recommended. The vaccine is a white/off-white lipid nanoparticle suspension having the following components.
Active Ingredient:
100 mcg mRNA-1273
Lipid Formulation Components:
1.93 mg lipids, which are made up of the following four (4) components.
SM-102 (a proprietary ionizable lipid)
Three known lipids
PEG 2000 DMG: polyethylene glycol (PEG) 2000 dimyristoyl glycerol (DMG)
Cholesterol
DSPC: 1,2-distearoyl-sn-glycero-3-phosphocholine
Buffering/Solubilizing Components:
0.31 mg tromethamine
1.18 mg tromethamine hydrochloride
0.043 mg acetic acid
0.12 mg sodium acetate
43.5 mg sucrose
Water (amount not given)
That ingredient list might not be very satisfying. Let us see if we can break down those components.
mRNA-1273: The active ingredient, mRNA-1273 is a messenger ribonucleic acid (messenger RNA or mRNA) that encodes for pre-fusion stabilized Spike (S) protein of the SARS-CoV-2 virus. mRNA tells the body what kind of protein the make via a process called translation that occurs in the ribosomes of human cells. The S protein is located on the outside of the SARS-CoV-2 virus. Once produced by the body, the S protein is seen as a foreign protein and the human body’s immune system responds to attack it (e.g., by generating antibodies). By causing the human body to develop an immune response to the S protein, the vaccine is, in effect, causing the body to develop an immune response to the virus itself without the presence of the entire virus. So, the mRNA causes the patient’s body to produce the S protein, which in turn causes an immune response. This is amazing technology. By the way, the 1273 is Moderna’s designation of the mRNA.
Moderna’s website has a great description of how mRNA works.
The problem with mRNA is that one cannot simply put it in a pill to be swallowed. mRNA needs to be protected to allow it to be delivered to the cells that will produce the S protein. It is known that lipid nanoparticles (LNP)(really small particles of various fatty molecules) can encapsulate mRNA. Since the LNP is structurally similar human cell membranes, the LNP can fuse to cell membranes and deliver the mRNA to where the body will respond to the instructions contained in the mRNA.
The LNP that encapsulates and delivers mRNA-1273 has four lipid components.
SM-102: SM-102 is a proprietary, ionizable lipid. I was unable to discover what this lipid is exactly. Moderna has published a paper on amino lipids that can be used to encapsulate mRNA, so it is likely one of those listed in the paper. For our purposes, let us call it the secret sauce of Moderna’s LNP.
PEG 2000 DMG: The second component contains several pieces. PEG 2000 is about 45 units of ethylene glycol (-CH2CH2O)44-CH2CH2OH). DMG is dimyristoyl glycerol, which means two molecules of myristic acid (1-tetradecanoic acid, a 14-carbon carboxylic acid) are attached to two of the three hydroxyl groups of glycerol (HOCH2CH(OH)CH2OH). The remaining OH group of glycerol is attached to the PEG 2000 moiety.
Cholesterol: Yes, that cholesterol. It is a type of lipid known as a sterol (a modified steroid). Its chemical formula is C27H46O.
DSPC: The last lipid ingredient, like with PEG 2000 DMG, contains several pieces. This time there are two molecules of stearic acid (1-octadecanoic acid, an 18-carbon carboxylic acid) attached to two of the three hydroxyl groups of glycerol. The remaining OH group of glycerol is attached to the phosphocholine moiety -PO4(-)-CH2CH2N(+)(CH3)3. Turns out, phosphocholine (also called phosphatidylcholine) is a component of cell walls. DSPC must be present to help the LNP fuse with cellular membranes.
The remaining five ingredients are part of the buffering/solubilization solution.
Tromethamine/tromethamine hydrochloride: Tromethamine (2-amino-2-(hydroxymethyl)propane-1,3-diol) and its hydrochloride (HCl) salt are components of a buffer called “Tris.” This is a common buffer used for biological pHs (~7). Buffers, by the way, are chemicals that help stabilize a pH.
Acetic acid/sodium acetate: If you have smelled vinegar, then you have smelled acetic acid (CH3COOH). The combination of acetic acid and its sodium (Na) salt are also common components in a biological buffer.
Sucrose: You also know this one. It is table sugar. One presumes this is added to help stabilize the suspension.
Water: Highly purified H2O.
There you have it. Let us hope that millions of people receive a COVID-19 vaccine like Moderna’s with in the next few weeks.
Stay tuned next week as we will investigate how Moderna’s patent portfolio relates to its vaccine.