As an academic discipline, put bluntly, "medicine" is a "discipline founded on structural thought suspension," or more precisely, an "ecology of human beings whose capacity for thought has been suspended."

The "suspension of thought" referred to here does not signify intellectual laziness as it is commonly understood.

Rather, it refers to the very structure of power through which the system called medicine strips human beings of their capacity for reflective thought and value judgment, incorporates them into the inner shell of scientific discourse, and renders ethical hesitation institutionally dysfunctional. What takes place here is not a "lack of thought" but a "structural loss of thought."

Medicine as a discipline does not in principle address the irreversible distance between the description of facts (is) and the ethical imperatives (ought), the so-called "is-ought gap" known since Hume.

More precisely, medicine does not "not address this gap," but "cannot deal with it," and therefore treats it as if it did not exist from the outset. The institutional technique that medicine has developed over many years is an operational system that instantaneously converts experiences into norms, linking explanation (is) and justification (ought) without epistemic or ethical mediation.

In other words, medicine transforms scientific descriptions (is), such as facts, statistics, and trends, directly into ethical imperatives that constrain human action (ought), and conceals this logical leap through the repeated invocation of the vocabulary of "scientific evidence."

Statements such as "there is scientific evidence" or "read the paper," frequently uttered by medical professionals, are emblematic of this operation.

Here, the fundamental question such as "Does science generate norms?"is bypassed, and "being scientific" is simply equated with "being that which must be obeyed.

Within this void, discussions concerning "human dignity" degenerate into formal rituals and are rendered thoroughly powerless at the level of practice.

What medicine performs is not the elimination of value judgments, but the disguising of value judgments in scientific language.

Within medicine, value judgments are made to appear as if they were extensions of factual statements, and a normative command, "one ought to obey because there is scientific evidence," is thereby constructed.

Yet behind this, there is neither any visibility of value judgments nor any ethical deliberation. This command demands an immediate leap from explanation to justification, and as a result, individual citizens are forcibly positioned within a binary of "obey / disobey." This is, quite clearly, a governing rationality that is ethically unjustifiable.

Medicine monopolizes the "authority to define health" and, under the name of science, transfers to the system those fundamental domains of judgment that should properly belong to citizens, such as "what is good," "what constitutes dignity," and "what it means to be human."

What is present here is a privatization of value judgments under the guise of science, and a systematic usurpation of ethical autonomy.

-1/5- In ethics, there exists a position known as ethical naturalism (particularly within neo-Aristotelian strands), which holds that norms must, to some extent, refer to facts.

However, medicine does not assume a relation between fact and norm, but dispenses with the reasoning process altogether. In this domain, reasoning disappears, and within the system, "facts" and "norms" are treated as identical.

Scientific descriptions are instantaneously converted into ethical imperatives, and any space for question, doubt, or contestation is foreclosed by the vocabulary of "scientific evidence."

Therefore, what medicine commits is not the naturalistic fallacy (the erroneous inference from fact to value), but a naturalistic fiat (the institutional decree that fact is value).

This does not mean that reasoning is mistaken, but that reasoning is precluded from the outset. Value judgments are concealed behind scientific vocabulary, and institutional language is translated into ethical justification.

The central question that emerges within this structure is, "Can scientific evidence be converted into ethical basis?"

I have yet to encounter a medical professional who vocally invokes "scientific evidence" provide a coherent argument that bridges such evidence to ethical justification.

They operate under the tacit assumption that "being scientific" automatically entails "being ethical." And the repeated invocation of that vocabulary functions as an apparatus that conceals the abnormal leap from fact to norm.

The fictions medicine must maintain in order to present itself as "scientific practice" are as follows:

1.Scientific evidence is value-neutral.
2.Guidelines arise from scientific evidence.
3.Therefore, the guidelines are neutral.
4.They are the most scientific.
5.Therefore, they are the most rational.
6.Therefore, adhering to them is ethical.
7.Therefore, those who do not adhere are "unscientific," "irrational," and "unethical."

Yet the structure that actually operates is the reverse:

1.Scientific evidence depends on the value choices of expert groups.
2.Guidelines are products of value choices and social compromises.
3.Neutrality is institutionally constructed.
4.Scientific discourse serves as an apparatus to neutralize the guidelines.
5.Rationality is a subordinate concept to value judgments.
6.Individual dignity is subordinated to the rationality of the system.
7.Autonomy and subjectivity are erased by institutional necessity.

In this way, "being scientific" is directly replaced by "ethical superiority." What medicine establishes is not ethics but the systemic outsourcing of value judgment to institutional authority.

-2/5-

#CTCCTCGGCGGGCACGTAG
- The Problematic 19-Nucleotide Sequence in the Moderna Patents

It is known that the COVID-19 virus includes the nucleotide sequence "CTCCTCGGCGGGCACGTAG" in its "Furin Cleavage Site," and that Moderna has the reverse complementary sequence of this in the Sequence Listing attached to their patent specification. The reverse complementary sequence to it is "CTACGTGCCCGCCGAGGAG."

MSH3 Homology and Potential Recombination Link to SARS-CoV-2 Furin Cleavage Site
frontiersin.org/journals/virol…

It is said that the probability of the sequence "CTCCTCGGCGGGCACGTAG" naturally appearing in COVID-19 is to be "3e-11." There have been objections raised about this probability, but since it does not affect my post, I do not consider it important here.
frontiersin.org/journals/virol…

If there are perpetrators, their confessions will reveal everything, and thus in this context, discussing probabilities is meaningless. Rather, I would emphasize that we should give more consideration to the patents disclosures regarding this issue.

1/16
The following five Patents 1 to 5 (Patent Publications), each includes the reverse complementary sequence "CTACGTGCCCGCCGAGGAG" in their Sequence Listing.

1. Patent 1: US9149506B2
patents.google.com/patent/US91495…
2. Patent 2: US9216205B2
patents.google.com/patent/US92162…
3. Patent 3: US9255129B2
patents.google.com/patent/US92551…
4. Patent 4: US9301993B2
patents.google.com/patent/US93019…
5. Patent 5: US9587003B2
patents.google.com/patent/US95870…

However, no Patent rights have been granted for the reverse complementary sequence itself. Therefore, we must carefully explain this issue to avoid misleading the public.

Regarding the above Patents 1 to 5, by referring to the "We Claim" section (the scope of the claims) at the end of each specification, we can determine the scope of the patent rights.

As will be explained later, the SEQ ID containing "CTACGTGCCCGCCGAGGAG" is "SEQ ID 11652." As we can see in the "We Claim" section, there is neither a description for "SEQ ID 11652" nor for "CTACGTGCCCGCCGAGGAG."

From this fact, we can understand that the patent rights have been granted to different SEQ IDs, and patent rights have NOT been granted to the reverse complementary sequence.

Let's take a look at some more specific information about the Patents 1 to 5.

2/16

MANUFACTURER’S CONVENIENCE

The FDA Briefing Document. Vaccines and Related Biological Products Advisory Committee Meeting September 19, 2012: Cell Lines Derived from Human Tumors for Vaccine Manufacture.

ntrl.ntis.gov/NTRL/dashboard…

This FDA document teaches us the risks associated with the residual DNA. Let's take a look at some interesting statements about the regulation value of 10 ng for the residual DNA.
----------------------
Deliberations of a WHO Study Group in 1997
The value of 100 pg of host cell DNA per vaccine dose remained the recommended standard for a decade. However, the issue was revisited in 1997 for several reasons.

First, vaccine manufacturers could not always meet this level of residual cell-substrate DNA for some viral vaccines, such as with certain enveloped viruses. Second, more information was available as to the oncogenic events in human cancers, where it has been established that multiple events, both genetic and epigenetic, are required (31, 32, 89, 98, 99).

And third, for continuous non-tumorigenic cell lines such as Vero, the major cell substrate that was being considered at the time, the presence of activated dominant oncogenes in these cells was unlikely.

The outcome of the 1997 WHO meeting was that the amount of residual cell-substrate DNA allowed per dose in a vaccine produced in a continuous cell line and one administered by the parenteral route was raised from 100 pg to 10 ng (10).
----------------------

When the first to third reasons are applied to the DNA wrapped in the LNP (LNP-DNA), the second and third reasons are not appropriate for the LNP-DNA because they did not take the LNP into account. The LNP had not yet been invented in 1997.

That is, for the LNP-DNA, the regulation value of 10 ng is based solely on the first reason, "manufacturer's convenience." This FDA document contains multiple sources of information and will be of public interest.

Incidentally, in my field, it is commonly believed that Arbutus Biopharma Corp holds the dominant patent US8058069B2 for the LNP. This patent was filed on April 15, 2009, and granted on November 15, 2011.

patents.google.com/patent/US80580…

Original Antigenic Sin: From BioNTech Patent

I posted an article about this issue on September 10, 2024, but I post this once again in detail because this is very important information involving a legal self confession regarding the original antigenic sin posed by BioNTech.

This issue has already been incorporated into four lawsuits in Germany by @AnwaltUlbrich san. I would like to share this information widely with politicians, lawyers, experts and you as one evidence of the disadvantages posed to society by the BioNTech-Pfizer vaccine BNT162b2.

BioNTech has filed a patent WO2024/176192A1 relating to the immune imprinting caused by the BNT162b2, and supports the paper "Immune imprinting and SARS-CoV-2 vaccine design (Wheatley et al)" in their patent.

◆BioNTech Patent WO2024/176192A1
patents.google.com/patent/WO20241…
Application Date (Priority Date): February 24, 2023
Publication Date: August 29, 2024
The lead inventor: Uğur Şahin, CEO of BioNTech.

◆Immune imprinting and SARS-CoV-2 vaccine design (Wheatley et al)
cell.com/action/showPdf…

The immune imprinting is also known as the original antigenic sin. The immune imprinting is a phenomenon in which a previous (e.g., initial) exposure to a first strain or variant of an infectious agent impedes development of an immune response against subsequent strains or variants of an infectious agent. Therefore, the immune imprinting can be associated with the spread of infection and the onset of severe symptoms in the vaccinated persons.

Wheatley et al say in the abstract of the paper as follows:
Reformulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines with variant strains is being pursued to combat the global surge in infections. We hypothesize that this may be suboptimal due to immune imprinting from earlier vaccination or infection with the original SARS-CoV-2 strain. New strategies may be needed to improve efficacy of SARS-CoV-2 variant vaccines.

In response to this, BioNTech says in their patent as follows:
[0003]…The emergence of these novel circulating variants of SARS-CoV-2 has raised significant concerns about the temporal efficacy of vaccine interventions.
[0006]…Further discussion of the imprinting phenomenon in the SARS- CoV-2 context can be found in Wheatley et al., Trends Immunol, 2021, the contents of which are incorporated by reference herein in their entirety.

BioNTech's view appears to be significantly different from that of government officials, who have touted the vaccine as "safe and effective."

@FLsurgeonGenn , @AnwaltUlbrich , @JikkyIeaks , @BanounHelene , @StatChrisCotton , @john_bumblebee , @ClareCraigPath

1/4 Uğur Şahin, the CEO of BioNTech, has been aware of the problem of the immune imprinting posed by their vaccine at least since February 24, 2023. Despite this, BioNTech did not stop supplying the vaccine and did not deter politicians and experts who recommended booster vaccinations.

The BNT162b2 was introduced into society in a way of a two-dose-vaccination set, which adequately and surely ensured that vaccine recipients were endowed with Wuhan-type antibodies.

BioNTech subsequently tried to overcome the immune imprinting by means of the bivalent vaccine and the other vaccine for specific mutant strain, but those have all failed as they could not suppress the increase of Wuhan-type antibodies.

Their solution to the immune imprinting is described, for example, in the Claims 1 and 5 to 8.

2/4

少し調べてみました。今後の調査の参考になればと思いますが、不明な点だらけですので軽い気持ちでお読み下さい。

１．論文

２．治験概要資料

３．論文補足資料

４．ＰＭＤＡ資料


論文で死亡例が言及された「フェーズ３ｂ」は、第１シリーズ（１日・２９日の２回接種）と第２シリーズ（９２日・１２０日の２回接種）に分かれていて、第１と第２で接種対象が入れ替わるようです。

第１シ：ワクチン２回→第２シ：プラセボ２回
第１シ：プラセボ２回→第２シ：ワクチン２回

イメージはＰＭＤＡ資料と治験概要資料からnature.com/articles/s4146…
classic.clinicaltrials.gov/ct2/show/NCT05…
static-content.springer.com/esm/art%3A10.1…
pmda.go.jp/drugs/2023/P20…
論文では、フェーズ３ｂで、ワクチン接種者５名、プラセボ接種者１６名の計２１名が死亡したと報告されています。これは、第１シリーズ後の結果で、第２シリーズの結果は含まれていないようです。

２１件のうち１０件がＣＯＶＩＤ－１９による感染死です。

内訳
ワクチン接種者：５人中１人が感染死、４人は別死因
プラセボ接種者：１６人中９人が感染死、７人は別死因

治験（フェーズ３ｂ）での死亡の定義は、「治験概要」に記載されているのですが、この定義通り運用されているのかは、確信を持てません。

治験概要


副次的結果の評価
９． ＣＯＶＩＤ－１９による死亡者の参加者数[期間:３７日目から９２日目]
プールされたフェーズ１/２/３ａ/３ｂフェーズ３ｂ参加者:研究ワクチンの２回目投与の７日後を起点に、以前の感染の証拠がない参加者におけるＣＯＶＩＤ－１９による死亡が発生した参加者数。

この定義で運用される場合、第１シリーズの２回接種を１セットとして７日後から感染死のカウントがスタートすると解釈されます。除外された感染死者が存在する場合、別の死因に分類されるのでしょうか？

（１）３６日までの感染死は除外？
（２）３７日から９２日で既感染者の感染死は除外？
（３）２回目投与から７日までの感染死は除外？
（４）１回目接種後の感染死は除外？
（５）９２日以降は未カウント？classic.clinicaltrials.gov/ct2/show/NCT05…

@Kevin_McKernan, @DJSpeicher, @Jikkyleaks
This time, I newly discovered BioNTech patent regarding a relationship between GTP/UTP concentrations and dsRNA, and hence I would like to report this here (#PlasmidGate, #BlotGate, #HumpGate, #PrionGate).

I previously reported BioNTech patent US20230183769A1 regarding the ATP and CTP concentrations in connection with the Process 2 (ref. 1). Reference links will be attached at the end of this series of posts.

To briefly summarize this, by adjusting the ATP and CTP concentrations, BioNTech increased the yield of RNA, decreased the amount of the dsRNA contamination, and increased the amount of the residual DNA contamination. That is, their vaccine is a product full of compromises.

The patent publication number this time is WO2022122689A1 (ref. 2).

This would be a successor patent to the above patent US20230183769A1. The patent filing date is December 7, 2021, and the patent publication date is June 16, 2022. The family of this patent is as attached. This patent have not discovered for about two years after its publication, and thus this shows how difficult it is for the public outside the patent field (even me) to search for the specific patent.

This patent discloses contents that support the contents of the EMA document (ref. 3) and that are along with the paper including Katalin Karikó as the one of authors (ref. 4).

Furthermore, this patent also mentions the production of abnormally long mRNA due to an "RNA backfolding", which is not disclosed in those documents. Further verification of the "RNA backfolding" will be required.

This patent primarily teaches risks associated with the dsRNA and a method for reducing the dsRNA. Note that the mRNA vaccine with a relatively large amount of the dsRNA contamination had been actually introduced into the human body in the early stages (Emergency Supply, etc.), as shown in the attached Table. S 2.6-13.

Surprisingly, the Table 5-1 attached in the patent is the completely same as the Table S. 2.4-1 attached in the EMA document (see attached image), and therefore, first of all, the relevant parts of the EMA document are picked up as noteworthy points.

The tagline "safe and effective" has been used for the mRNA vaccine since its introduction. Please think about why it was necessary to reduce the amount of the dsRNA contamination after its introduction, even though the mRNA vaccine is "safe and effective," through this post.

1/12


Regarding the relationship between the GTP and UTP concentrations and the dsRNA, the EMA document states as follows:

For the current process, linearized plasmid DNA template was chosen for scalability in order to feasibly supply the current vaccine needs. The GTP and N1-methylpseudo UTP starting concentrations are controlled at a low target and these solutions are delivered as bolus feeds. These ribonucleotides were chosen to be limiting reagents to aid in capping and to reduce potential dsRNA impurities. The 5’-cap is in stoichiometric excess to the GTP to enable the preferential incorporation of the 5’-cap as the first addition to the RNA transcript. Dditionally, controlling the N1-methylpseudo UTP concentration in the reaction is proposed to reduce the dsRNA impurities.

That is, it is understood that BioNTech (Pfizer) set the GTP and UTP concentrations in relatively low values to reduce the amount of the dsRNA contamination. The production mechanism of the dsRNA and its composition are unknown here.

Note that the EMA has sharply pointed out to BioNTech (Pfizer) for not adequately explaining the lower limits of the ATP and CTP concentrations.

Initially, addition volumes for ATP and CTP were identified as non-CPPs as both were supplied in theoretical excess. Following the Pfizer GMP campaigns and additional smalls cale studies it was shown that these volumes could be limiting and the ranges were widened at the higher end. The approach to only change the higher end of the ranges is not understood. It is also noted that after the adjustment of these volumes the RNA integrity levels increased (see also discussion below in relation to the comparability study).

・It is noted that the ranges studied for addition volumes for CTP and ATP as stated in 3.2.S.2.6 are 81.0-143.8 and 90.0-135.1 mg/L respectively and that the acceptable ranges proposed are 85.4-143.8 and 85.4-135.1 mg/L. It seems as if the lower acceptable range of 85.4 mg/L proposed for ATP volume have not been studied, this needs to be clarified. In addition, it needs to be justified why the lower end of the ranges for both CTP and ATP volumes remained unchanged although the target ranges were increased (from 90 to135.1 and 107.9 mg/L respectively), to avoid that these nucleotides will be limiting in order to increase the percentage of the RNA integrity.
These ranges need to be further justified and clarified and the dossier updated accordingly.

2/12

Here is a List of "Insertional mutagenesis" patents of Moderna. The patents are categorized by patent family.

NOTE:
For convenience, I have extracted the International patents (WO), the European patents (EP), and the United States patents (US), and other patent families including Australian patent (AU), Japanese patent (JP), Chinese patent (CN), etc., are excluded from this list.

The patent search requires an advanced know-how (unfortunately I don’t have), so there is no guarantee that all patents are correctly extracted, and there may be patents missing from this list. If you find a Moderna patent relating to "Insertional mutagenesis," please let me know to create a list that serves the public interest. That will be reflected in the following list. @zombiemommy

UPDATE: Patents of Stephane Bancel, Moderna CEO
I further searched for his patents and categorized them by patent family. Some patents do not include him as an inventor although they belong to the patent family. The patent families I'm interested in are highlighted by markers, etc.

For convenience, I have extracted the International patents (WO), the European patents (EP), and the United States patents (US), and other patent families including Australian patent (AU), Japanese patent (JP), Chinese patent (CN), etc., are excluded from the list.

NOTE: The patent search requires an advanced know-how (unfortunately I don’t have), so there is no guarantee that all patents are correctly extracted. Therefore, there may be patents missing from this list. If you find a patent of Stephane Bancel, please let me know to create a list that serves the public interest. That will be reflected in the following list.

I extracted 67 patent applications that contain at least one term of BNT162b1, BNT162b2 and BNT162b3 from BioNTech patent applications, and categorized them based on the patent families (see the attached list). From the number of the patents, the families 1 to 3 seem to be comparatively important.

Since these patents relate to the implemented products, they may disclose matters that are not disclosed in the examination documents, the EMA document and the TGA document. The list includes the patents I have already mentioned, such as the patent regarding the late migrating species and the patent regarding the CTP/ATP concentrations.

Patent families do not necessarily disclose the same content, and some patents within a patent family do not include BNT162b1, BNT162b2 and BNT162b3. Also, some of the patents in the list include BNT162a and/or BNT162c as well.

FYI:
BioNTech is developing five types COVID-19 mRNA vaccines:
(1) BNT162b1: Nucleoside-modified mRNA (secretory spike RBD)
(2) BNT162b2: Nucleoside-modified mRNA (transmembrane prefusion spike)
(3) BNT162b3: Nucleoside-modified mRNA (transmembrane spike RBD)
(4) BNT162a1: Unmodified mRNA
(5) BNT162c2: Self-amplified mRNA (next generation replicon vaccine)

For convenience, I have extracted the International patents (WO), the European patents (EP), and the United States patents (US), and other patent families are excluded from the list.

The patent search requires an advanced know-how (unfortunately I don’t have), so there is no guarantee that all patents are correctly extracted. Therefore, there may be patents missing from this list. If you find a patent containing at least one term among the BNT162b1, the BNT162b2 and the BNT162b3, please let me know to create a list that serves the public interest.

I extracted 109 Moderna patents including Stephane Bancel as one of inventors through a patent search. In reality, I only briefly checked it and didn't examine the contents carefully, so I look forward to further verification by volunteers. There were also some slightly unusual patents.

Although I couldn't find any particularly new findings, let me report this as one result (see attached list). The patent publication numbers in the list are shown in chronological order from No. 1 to No. 109.

So far, we have found the following (1) to (3) Stephane Bancel patents.

(1) The inheritance of the DNA integrated into the genome to offspring
(2) The endotoxin
(3) The residual DNA fragment (underestimation in the qPCR)

According to the list, the patents related to (1) occupy approximately 2/3 of the total, making up the majority. So, this indicates that Stephane Bancel concerned about the integration of the DNA into the genome.

We may consider these patents (1) to (3) to be patents with fatal confessions from Stephane Bancel.

However, the patent search doesn't guarantee that all patents including Stephane Bancel as an inventor are properly extracted, so the possibility that there are patents omitted from the search cannot be ruled out.

Also, some of the 109 patents are considered to constitute patent families derived from the same patent applications (particularly the patent group (1)). In order to exceed the realistic work time, I didn't go as far as checking the patent families in this work. Therefore, it is possible that other patents including Stephane Bancel as an inventor exist.

If you find any Stephane Bancel patent that is not in this list attached here, please let us know.

Theme: Masterpiece of craftsmanship and Sleeping lions

Regarding BioNTech's patent US2023/0183769A1 I previously posted, which admittedly increases the residual DNA, I would like to emphasize another point here.

Please compare the descriptions of the patent and the EMA document as reproduced below. The two documents say almost same thing, but ''something'' is missing from the EMA document.

EMA document (P. 44）
In parallel, small scale studies were conducted to understand the impact of a wider range of CTP and ATP, since ATP was identified as the next potential limiting nucleotide. Results showed that increasing the volumes of both CTP and ATP not only mitigated these nucleotide limitations, as measured at the end of the proteinase K step, but also increased integrity and yield and decreased dsRNA. Therefore, ATP and CTP volumes were identified as CPPs prior to the Pfizer PPQ3 batch. As a result of the small scale studies, acceptable ranges for ATP and CTP volumes were widened at the higher end from 99.0 to 143.8 mL/L starting IVT volume for CTP and 99.0 to 135.1 mL/L starting IVT volume for ATP.…

Patent (para [0437])
[0437]
The present example demonstrates additional exemplary assessment of IVT reactions mixtures. FIG. 16 summarizes exemplary IVT reaction mixtures assessed and exemplary characterization of produced RNAs when CTP in the IVT reaction mixture is increased. Both RNA yield and integrity increased with higher CTP starting concentrations, while dsRNA content decreases with higher CTP concentration. Residual DNA was increased with higher CTP starting concentration (FIG. 16 ). Without wishing to be bound by any one theory, residual DNA may have increased with higher CTP starting concentration due to activity of DNAse I being decreased from, for example, lower free magnesium cation levels.

-1- Pfizer (BioNTech) states in the EMA document the benefits of improving the RNA yield and integrity and decreasing the dsDNA by increasing CTP and ATP concentrations. Despite this, Pfizer (BioNTech) concealed the fact that "residual DNA increases" in it.

In the EMA document, comparing the batch C501 with the previous batches C101 to C401, it can be seen that the residual DNA amount has increased nearly 10 times. However, from only the EMA document, it is not possible to understand whether this was due to the variations between batches or whether this was just coincidentally increased.

However, by touching this patent disclosure, it can be understood that this increase in the residual DNA is the intended result based on the design of Pfizer (BioNTech).

Why is the residual DNA amount of the Pfizer higher than that of the Modelna?
One of the answers may be the fact that they concealed in the EMA document.

They already knew that the residual DNA would be high at the time of manufacturing. And knowing this, they introduced the vaccine into the society and vaccinated many citizens.

If they had conscientious moral principles based on the medical philosophy, then they would have designed the product to minimize the residual DNA. But not only did they not do that, they concealed the fact in the EMA document.

The qPCR they employed to measure the residual DNA amount underestimates it by its nature. That is, with the qPCR, they underestimated the increased residual DNA due to the manufacturing process.

Their actions like this are truly a masterpiece of craftsmanship.

This kind of the attitude from a pharmaceutical company should not be tolerated, and EMA should also be blamed for its thoughtless attitude in overlooking this.

@Kevin_McKernan
We discovered a pivotal new patent application related to the EMA document. We call further verification for this patent by experts and volunteers.

The DNA contamination is a major concern in the mRNA vaccine technology. The patent we discovered this time discloses a novel method to increase not only the quality and yield of the RNA but also the residual DNA. This suggests that this method is one of major causes of the DNA contamination in the mRNA vaccines.

The patent publication number is US20230183769A1. All links will be attached to the last post.

The US20230183769A1 was filed on August 23, 2022, and published on July 23, 2023. This patent application has not been registered yet.

This patent discloses experiments underlying the EMA document on BNT162b1 and BNT162b2 of the BioNTech (Pfizer), and will reach to one cores of the residual DNA contamination problem.

If it is based on the disclosures of this patent and the EMA document, BioNTech and Pfizer recognize that their manufacturing method increases the residual DNA.

That is, BioNTech (Pfizer) makes the residual DNA amount look extremely small by adopting the qPCR that underestimates the residual DNA amount and the fluorometry that overestimates the RNA amount while adopting the manufacturing method that inevitably increases the residual DNA.

-1- BioNTech articulates the trade-off between an improving the RNA quality and an increasing the residual DNA in relation to a concentration of CTP (cytidine triphosphate), in the para [0437] and the figure 16 of this patent.

[0437]…Both RNA yield and integrity increased with higher CTP starting concentrations, while dsRNA content decreases with higher CTP concentration. Residual DNA was increased with higher CTP starting concentration (FIG. 16).

BioNTech makes the following assumption regarding the increase in the residual DNA.

[0437]…Without wishing to be bound by any one theory, residual DNA may have increased with higher CTP starting concentration due to activity of DNase I being decreased from, for example, lower free magnesium cation levels.

The figure 16 shows the residual DNA amounts measured at the concentrations of CTP of 0%, +10%, +20% and +50%. These concentrations correspond to the IVT conditions indicated in the EMA document. The overall process conditions in the figure 16 are disclosed in Table 2.1.

According to the EMA document, BioNTech uses a rough calculation that assumes a uniform denominator of 30 ug when calculating the residual DNA amount. Therefore, the residual DNA amount shown in the figure 16 is probably calculated following that calculation method.

On the other hand, BioNTech discloses the specific amounts of CTP and ATP (adenosine triphosphate) in the paras [0341] and [0342]. In the Table 2.4, the amounts of CTP is set to 144 mL/L starting volume. Those amounts match the amounts indicated as the acceptable ranges in the EMA document.

It is obvious that the acceptable ranges for the concentrations of CTP and ATP indicated in the EMA document are based on the experimental results disclosed in this patent. These acceptable ranges are the range that improve the RNA quality but increase the residual DNA.

-2-

Theme: Calling and challenging for quantitatively eliminating the underestimation of the DNA contamination in the qPCR

◆The estimated amount of the DNA contamination when the underestimation is eliminated significantly exceeds the regulation amount.

Regarding the Pfizer Wuhan-type vaccine according to the study of Buckhaults, the estimated amount of the DNA contamination of the lot number EL9262 is 109 [ng/dose], and the estimated amount of the DNA contamination of the lot number EL9264 is 79.4 [ng/dose]. Additionally, regarding the Moderna vaccine according to the study of Mckernan, the analogical estimated amount of the DNA contamination is 116 [ng/dose].

The problem of the plasmid DNA contaminations in the Covid mRNA vaccines was reported by McKernan in the substack on February 16, 2023, and the preprint thereof was filed on April 10 in the same year (ref. 1). In this preprint, three DNA contamination amounts were identified by means of three methods including the qPCR. It is known that the qPCR underestimates the DNA contamination amount due to natures of the mRNA vaccine manufacturing method and the measurement method.

For example, Moderna has self-acknowledged the underestimation of residual DNA (DNA contamination) in the qPCR in their patent US10077439B2 (ref. 2, p.16, section 19), and this discovery is still fresh in our minds. The filing date of this patent is March 13, 2014, before the outbreak of the new coronavirus, and one of the inventors of this patent is Stephane Bancel, the CEO of Moderna. Moderna also has explicitly self-acknowledged in this patent that the residual DNA is to be oncogenic and must be removed (p.7, section 1).

Furthermore, another Moderna patent US13/791922 (US20130259924A1, Stephane Bancel, et al.) has been incorporated into the above patent (ref. 2, p.10, section 8) by reference for all purpose teaches that the DNA introduced into a cell can be inherited by offspring (ref. 4, para [0006]). Additionally, the other Moderna patent US20190240317A1 teaches the insertional mutagenesis due to the naked plasmid DNA (ref. 5, para [0012]).

The above patent US10077439B2 (ref. 2) has cited the FDA guideline (ref. 6) in its end of the specification (p.18, section 24), and this FDA guideline teaches multiple risks related to the residual DNA including insertional mutagenesis, oncogenesis, and genetic integration (ref. 6, p.37).

It is obvious from those facts that the DNA contamination has a different mechanism of action from an originally intended mechanism of action of the vaccine, and it goes without saying that the DNA contamination may cause a fatal side effect on the human body.

Despite Moderna and FDA were aware of the above events, Moderna used the qPCR to detect the residual DNA amount in their actual manufacturing process for the mRNA vaccine (ref. 3, p.109), and FDA permitted it. They have continued to ignore the problem of residual DNA to this day even though they have been aware of the risks of residual DNA.

FDA has set the regulation amount of 10 [ng/dose] and below 200 [bp] for the DNA contamination (ref. 6, p.37). However, this is not the regulation amount for the residual DNA wrapped by the LNP (LNP-DNA), but for the naked DNA.

The LNP-DNA has superior long-term durability to the naked DNA and has the property of easily inducing the residual DNA into a cell. It is therefore obvious that the LNP-DNA has a different mechanism of action from that of the naked DNA, and it is extremely inappropriate for the previous regulation amount (=10 [ng/dose], <200 [bp]) to be directly applied to the new LNP-DNA technology.

However, since there is no regulation amount for the LNP-DNA, we cannot help but following the previous regulation amount for the naked DNA. An act of wrapping the residual DNA with the LNP and introducing it into the human body is an ethical issue and should not be permitted in any amount since safety cannot be guaranteed.

It goes without saying that their such acts were caused intentionally or through gross negligence as it is obvious from the above documents, and thus such fatal flaws in the regulatory authorities are needed to be rigorously pursued.

The underestimation in the qPCR is a fundamental problem that directly relates not only to the regulated amount of the DNA contamination but also to human life, and thus to quantitatively eliminate it means a great advance in the DNA contamination problem.

Researchers focusing on the problem of DNA contamination have been aware of the underestimation caused by the qPCR but have not made any efforts to eliminate it. Researchers should not turn away from this underestimation problem and should take a stand toward eliminating the underestimation.

We intensively investigated a method to eliminate the underestimation based on the experimental results disclosed by McKernan and Buckhaults. The purpose of this post is to provide a first step for eliminating the underestimation in the qPCR.

The estimated value at present point shall now be disclosed hereinafter, but a certain correction value may be added depending on future experimental results, etc. However, we believe that a method for eliminating the underestimation has been established to some extent and disclose this here.

We also believe this post will provide deep insights and further perspectives on the DNA contamination problem to many researchers. We expect that excellent researchers will give further consideration to this.

This post updates and specifically explains the calculation method for the DNA contamination shown in the past post from mbi (ref. 7).

@Kevin_McKernan
@P_J_Buckhaults
@DJSpeicher
◆Why is the DNA contamination amount underestimated?
The underestimation of the DNA contamination amount is caused by a manufacturing process of the mRNA vaccine and a process of the qPCR (FIG. 1). Specifically, the underestimation is mainly caused from the following three step.

(1) A cleavage step of the plasmid DNA with a DNase I treatment (Ref. 8, FIG. 2)
(2) A removal step of the plasmid DNA fragments smaller than a certain size with an ultrafiltration treatment
(3) A measurement step of the DNA fragments larger than a certain size with the qPCR

The steps (1) and (2) are included in the manufacturing process flow of the mRNA vaccine and are performed after a synthesizing step of the spike mRNA from the plasmid DNA. The step (3) is included in the process flow of the qPCR.

(1) The cleavage step
In this step, the plasmid DNA (=7754 [bp]) is cleaved into a predetermined average size with the DNase I treatment. That is, the qPCR targets are also cleaved into a certain probability, and therefore total numbers of intact qPCR targets (probes) are to be reduced. The qPCR targets are a part of a spike region (i.e., spike target=114 [bp]) and a part of an origin region (i.e., origin target=106 [bp]) (FIG. 2).

(2) The ultrafiltration step
In this step, small DNA fragments not more than a predetermined size (=100 [bp] or less) among the DNA fragments cleaved in the cleavage step are to be removed. In this step, the intact qPCR targets (=114[bp], 106[bp]) are to be remained whereas the cleaved target fragments are to be removed. Note that all small DNA fragments are not necessarily removed in this step.

(3) The measurement step
In this step, the DNA contamination amount is measured based on the qPCR targets. Therefore, the DNA fragments smaller than the target size (114 [bp], 106 [bp]) cannot be detected in the qPCR.

Those steps (1) to (3) all lead to the underestimation of the DNA contamination amount. Hereinafter, a specific method for eliminating the underestimation and calculating the estimated amount of the DNA contamination shall now be explained.

Moderna's patent application discloses much about the adverse behavior of the plasmid DNA in the body. Previously discussed US2019240317A1 discloses the insertional mutagenesis due to the naked plasmid DNA.



Moderna's another patent US10077439B2 discloses an invention relating to a removal process of DNA fragments in an mRNA production, and the background of this invention discloses as follows:

The DNA template used in the mRNA manufacturing process must be removed to ensure the efficacy of therapeutics and safety, because residual DNA in drug products may induce activation of the innate response and has the potential to be oncogenic in patient populations. Regulatory guidelines may also require the quantification, control, and removal of the DNA template in RNA products. Currently available or reported methods do not address this deficiency.



As it is clear from the title of the invention and the entire disclosure of the specification, the DNA template and residual DNA mean the plasmid DNA fragments. The DNA template is defined as the plasmid DNA in the specification as one example, and the plasmid DNA fragments are interpreted as those generated by the DNase I treatment.

The US10077439B2 will provide a good combination for the US2019240317A1.

The problem of the plasmid DNA fragments is actually an old and common problem in this field, but it is worth investigating Moderna's patent in that it legally shows that Moderna has been aware of this problem.

In particular, in the Moderna's patent application, there are some careless statements in the background of the invention section, so there is a possibility that even more interesting information can be obtained.

Reading patent specifications can be difficult. However, even a layman can easily read the background of the invention section. The background of the invention section is basically disclosed at the top of the specification.

If you have the opportunity to touch the Moderna's patent and Pfizer's patent, I recommend that you read at least this section. You may make an amazing discovery.patents.google.com/patent/US20190…
patents.google.com/patent/US10077…
Further information

https://twitter.com/Patent_SUN/status/1725556303848972410

THEME: #CTCCTCGGCGGGCACGTAG
Moderna's 19 nucleotide sequence in patent

It is known that the COVID19 includes the nucleotide sequence of "CTCCTCGGCGGGCACGTAG" in its furin cleavage site, and that Moderna has the reverse complementary sequence thereof in the Sequence Listing attached to their patent specification. The reverse complementary sequence is "CTACGTGCCCGCCGAGGAG."

It is said that the probability that the "CTCCTCGGCGGGCACGTAG" naturally appears in the COVID19 may be "3e-11."



The following five patent publications ① to ⑤ each includes the above reverse complementary sequence in its Sequence Listing, but no patent rights have been granted to the reverse complementary sequence itself.

①US9149506B2
②US9216205B2
③US9255129B2
④US9301993B2
⑤US9587003B2

Therefore, we must carefully explain the reverse complementary sequence so as not to mislead the public. Regarding those patent publications ① to ⑤, by referring to the "We claim" section (scope of Claims) attached to the end of each specification, we can understand where the patent rights exist.

As we can see in each "We claim" section of the patent publications ① to ⑤, there is no description of "CTACGTGCCCGCCGAGGAG."

From this fact, we can understand that the patent rights have NOT been granted to it.

If you have different patent information regarding this, please let me know.

-1-




The Sequence Listing cannot be obtained just by obtaining the patent publications ① to ⑤.

How can we get and confirm the Sequence Listing?
We can obtain it by accessing the United States Patent Office () and entering any one of the following patent numbers ① to ⑤.

①US9149506B2
②US9216205B2
③US9255129B2
④US9301993B2
⑤US9587003B2

Amazingly, this Sequence Listing contains "33,915 number of SEQ IDs" consisting ridiculous "1,431,049 number of total lines."

The "CTACGTGCCCGCCGAGGAG" can be found in a part of "SEQ ID: 11652."

-2-seqdata.uspto.gov

Now, we can see a "transcendent horror" in a structure where the pseudouridine spike RNA (wine color in the attached diagram) protects the spike DNAs (green ORF19 & orange ORF11).

This is a so-called the GC rich DNA-RNA hybrid (R-Loop).

Strangely enough, for some mysterious reasons, the spike RNA protrudes from the spike DNAs to the ori DNA (vector DNA: lower yellow ori region), and protects even the ori DNA...

This structure is definitely a “Special Grade Cursed Object”...

Let's study “Special Grade Cursed Object” together by following Mr. Arakawa's blog quoting Dr. McKernan's Substack.





1/6


(1) The spike DNAs
① First, the spike RNA is processed by an RNase.

The spike DNAs are not degraded by the RNase. This is because the RNase does not degrade the spike DNAs but the spike RNA.

② Next, the spike DNAs are processed by a T5 exonuclease for degrading.

Even if the spike DNAs are processed by the T5 exonuclease, the decreasing amount of the spike DNAs are very small.

This suggests that the spike DNAs are protected by the spike RNA.

③ When the spike DNAs are degraded by the T5 exonuclease after the spike RNA is degraded by the RNase, the spike DNAs are extremely decreased to a detection limit🤯

That is, if the spike RNA is removed first, the spike DNAs can be significantly degraded due to no inhibitor.

It is thus understood that the spike RNA protects the spike DNAs and inhibits the degradation of the spike DNAs😱

2/6

Regarding the Pfizer's vaccine (omicron), 7 prion motifs have been confirmed in an ORF 11 region therein. This time, Mr. mbi (), who is a skilled person in the art, focused on an ORF 19 region and found 23 prion motifs in the ORF 19 region therein (#priongate).

The ORF 11 region and the ORF 19 region form an R-loop with a spike RNA (omicron). The ORF 19 region especially forms a GC-rich RNA-DNA hybrid with the spike RNA and is tightly bound to it.

According to @Kevin_McKernan's report, there is a concern that a hairpin effect of N1-methyl-PseudoU on the spike RNA causes a template switching phenomenon of a T7 polymerase, leading to a generation of a long mRNA including the ORF 11 region and the ORF 19 region.
()

That is, this concern means a production of an mRNA that includes the ORF 11 region having the 7 prion motifs and the ORF 19 region having the 23 prion motifs. This prion-engineered mRNA is encapsulated in an LNP and is floated in a vial. This means that the prion-engineered mRNA may be introduced into the human body through a vaccination.

As a further concern, Mr. mbi has pointed out an existence of G-quadruplexs integrated into the ORF 19 region. Surprisingly, the ORF 19 region has as many as 144 G-quadruplexes while it includes the 23 prion motifs.

The G-quadruplexs assist in an aggregation of denatured prionoids when they form the aggregate. Where the GC-rich RNA-DNA hybrid is formed, this activity is increased, and therefore the risk of a prion disease caused by the vaccination may be increased.

These are reports regarding the omicron-type vaccine, but he has confirmed that a similar trend can be seen in the Wuhan-type vaccine (Wuhan-type vaccine has more…). The prion disease after the vaccination has been reported from various countries. We hope that this discovery will help elucidate the cause of this.

#plasmidgate, #blotgate, #priongatetwitter.com/mbi92710920

https://twitter.com/Kevin_McKernan/status/1682521919612960768?s=20

Both of the ORF11 region and the ORF19 region have relatively large lengths. The probability of the presence of a DNA fragment including the ORF11 region in an intact state and/or a DNA fragment including the ORF19 region in an intact state therefore may be extremely low.

However, because the ORF19 region is tightly bound to the spike RNA, the ORF19 region may be present in the intact state. Therefore, the presence of the DNA fragment including the intact ORF19 should be examined precisely.

In the case of the DNA fragments contamination, it may be better to focus on smaller ORF regions having the prion motif. For example, ORF5, ORF16, ORF20, ORF22, ORF33, ORF36, and ORF37 include at least one prion motif. These ORF regions have 100 nt to 250 nt long (see attached), and therefore they are very likely to be present in the vial as the intact DNA fragments.

#plasmidgate, #blotgate, #priongate

Regarding the Pfizer's vaccine (omicron), 7 prion motifs have been confirmed in an ORF 11 region therein. This time, Mr. mbi (), who is an skilled person in the art, focused on an ORF 19 region and found 23 prion motifs in the ORF 19 region therein (#priongate).

The ORF 11 region and the ORF 19 region form an R-loop with a spike RNA (omicron). The ORF 19 region especially forms a GC-rich RNA-DNA hybrid with the spike RNA and is tightly bound to it.

According to @Kevin_McKernan 's report, there is a concern that a hairpin effect of N1-methyl-PseudoU on the spike RNA causes a template switching phenomenon of a T7 polymerase, leading to a generation of a long mRNA including the ORF 11 region and the ORF 19 region.
()

That is, this concern means a production of an mRNA that includes the ORF 11 region having the 7 prion motifs and the ORF 19 region having the 23 prion motifs. This prion-engineered mRNA is encapsulated in an LNP and is floated in a vial. This means that the prion-engineered mRNA may be introduced into the human body through a vaccination.

As a further concern, Mr. mbi has pointed out an existence of G-quadruplexs integrated into the ORF 19 region. Surprisingly, the ORF 19 region has as many as 144 G-quadruplexes while it includes the 23 prion motifs.

The G-quadruplexs assists in an aggregation of denatured prionoids when they form the aggregate. Where the GC-rich RNA-DNA hybrid is formed, this activity is increased, and therefore the risk of a prion disease caused by the vaccination may be increased.

These are reports regarding the omicron-type vaccine, but he has confirmed that a similar trend can be seen in the Wuhan-type vaccine (Wuhan-type vaccine has more…). The prion disease after the vaccination has been reported from various countries. We hope that this discovery will help elucidate the cause of this.

#priongate , #blotgatetwitter.com/mbi92710920







Both of the ORF11 region and the ORF19 region have relatively large lengths. The probability of the presence of a DNA fragment including the ORF11 region in an intact state and/or a DNA fragment including the ORF19 region in an intact state therefore may be extremely low.

However, because the ORF19 region is tightly bound to the spike RNA, the ORF19 region may be present in the intact state. Therefore, the presence of the DNA fragment including the intact ORF19 should be examined precisely.

In the case of the DNA fragments contamination, it may be better to focus on smaller ORF regions having the prion motif. For example, ORF5, ORF16, ORF20, ORF22, ORF33, ORF36, and ORF37 include at least one prion motif. These ORF regions have 100 nt to 250 nt long (see attached), and therefore they are very likely to be present in the vial as the intact DNA fragments.

#plasmidgate, #blotgate, #priongate