dsRNA, Residual DNA and a BioNTech Patent

Yield Always Trumps Purity

BioNTech Patent found by Patent_Sun on X

I don’t know who Patent_Sun is personally but he he is a thorough and very bright Japanese attorney who looks at and interprets patents and here he found a doozy.BioNTech Patent. He is well worth following on X.

First of all, the patent is by BioNTech, and not Pfizer. BioNTech has a few patents on manufacturing. Here you can see it is a method for making large amount mRNA via in vitro transcription (IVT). Here were the starting materials to make the modRNA via IVT in the EMA leak/hack with all the nucleotides needed, the 5’cap and the linear DNA template.

Patent Sun’s Review of the Patent

Patent Sun's Twitter Thread

Here is the patent explain the IVT process with excess CTP solution with the explicit goal of

1. enhancing capping efficiency (remember you need the 5’cap and poly A tail to make an intact mRNA strand and the plasmid DNA does not code for the 5’ cap; that is added during the IVT).

2. reduce dsRNA. THIS IS IMPORTANT BECAUSE dsRNA IS IMMUNOLOGIC

All this says is that more RNA was produced via IVT if they increased the nucleotides, especially of CTP during the process. Then the DNA is digestion and purification with magnetic beads. This is the Process 1 description.

Then they tried this method with the Process 2 batches where they increased the scale tremendously. As Patent Sun says, it is indeed instructive to read the EMA reviewer comments along with what BioNTech is proposing in the patent. I remember reading this paragraph and pondering this for many months. There were a few examples in the EMA leak/hack where the reviewer said “this process was NOT UNDERSTOOD.” (note ATP=adenosine triphosphate; CTP=cytidine triphosphate)

Yield or Purity?

Most importantly, BioNTech admits in the patent it is either YIELD OR PURITY.

What do you think BioNTech did? Yield trumps purity almost always if they can get away with it. And in this patented process of IVT, guess what? You get MORE RESIDUAL DNA IMPURITIES. This is at the CORE of the problem of the residual DNA in the Pfizer product (see red highlight). The explanation is that DNAse 1 activity is decreased because there is less magnesium ions lying around to run the reaction. So to get rid of the residual DNA they would have to change all their large scale IVT processes. Yikes.

My Eureka

This explains a few strange things about the purification of the mRNA that I could not understand. Remember, the whole goal of this patent is to DECREASE dsRNA.

1. BioNTech had patented a new method of removing dsRNA using ethanol and a cellulose filter Facile Method to Remove dsRNA but they did not use it when making the mRNA for the jabs. I couldn’t understand it, and thought maybe they had some super duper filters that filtered out the dsRNA at the end of the mRNA process.

   1. But IF, those filters were really good at getting rid of dsRNA, why didn’t they get rid of the residual DNA as well? No one could answer that.

2. BioNTech did not use any chromatography techniques to purify the mRNA as is considered standard. So after you make the mRNA and digest the DNA you can put your solution through a column and get rid of contaminants. Then you buffer and filter. Well BioNTech didn’t do any of that. Just buffered the solution and filtered it before sending it off to be encapsulated in the LNPs. Huh? Moderna did use chromatography though.

3. The varying amounts of residual DNA in both Process 1 and Process 2 lots. It sure looked like they were experimenting because the variation was SO LARGE. Well, guess what? They WERE experimenting, not to figure out how much DNA to put IN (sorry Pfizer but in this climate of course I thought you were doing it on purpose) but to keep dsRNA OUT.

Here are the levels of residual DNA for the Process 1 (those starting with R) and Process 2 batches (those starting with 20)

Ignore the first one for now. It was made separately from all other mRNA batches at the very beginning in mid-mark 2020. I have more to say on that later.

For Process 1 batches, the residual DNA starts a bit high and then they drop to very low levels. For Process 2 batches, they start low and then climb up. Here are Process 2 batches only.

Oh WOW. And here you can see as the residual DNA levels increase, then dsRNA decreases. That is what this patent is all about.

Why is purifying dsRNA so important?

Well, I have been beating the drum about dsRNA for a while and already explained it in a few substacks. But essentially, dsRNA is a mimic of viral genomes which results in a robust type 1 interferon production. This leads to the degradation of the cellular mRNA and ribosomal RNA. So dsRNA will overwhelm the cells and no spike protein will be produced. Can’t have that.

Besides, some people (including me) think lots of dsRNA might leads to myocarditis. Please read or at least skim over these posts to get the context of this patent and the importance of dsRNA.

Post on dsRNA and adjuvants

Forget the DNA, it's the dsRNA that is the problem

Implications?

1. Yield over Purity is Pharma’s credo, baby!

2. Take your pick. Residual DNA in BioNTech/Pfizer or dsRNA in Moderna

3. If the mRNA is too pure, then no antibodies, schmantibodies can be made

4. The regulators knew and defended this amount of DNA (and the high dsRNA in Moderna who gets away with it because there is no compendial standard for dsRNA yet) because, officially, it meets the guidelines.

5. FDA KNOWS this amount of DNA is a huge risk, but continues to deny it. In the background though I am sure they are working on it. Found a patent on this I think which needs another substack.

6. However, EVEN if Pfizer didn’t put in large amounts of DNA in the mRNA on purpose, THEY STILL HID THE SV40 SEQUENCES FROM EVERYBODY!!

KNOWINGLY, KNOWINGLY, KNOWINGLY

Pray the rosary.