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Mar 18

#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

Patent 1: US9149506B2

Inventor: Tirtha Chakraborty, Antonin de Fougerolles
Title of invention: Modified polynucleotides encoding septin-4
Filing Date: December 16, 2013 (Priority to US14/107,079)
Registered date: October 6, 2015
"We Claim" section: patents.google.com/patent/US91495…

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Patent SUN

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Nov 20, 2024

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…

Even looking at the citation 10, no specific information was found.

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).

10. Brown, F., E. Griffiths, F. Horaud, and J. C. Petricciani (ed.). 1998. Safety of Biological Products Prepared from Mammalian Cell Culture, vol. 93. Karger, Basel.

researchgate.net/publication/24…

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Patent SUN

@Patent_SUN

Oct 21, 2024

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

The BNT162b2 is a platform that encodes the full-length Spike, and this cannot be changed to the fragment including the RBD or the S1 domain. In this point, BioNTech has a history of failing to develop the BNT162b1 which targets the RBD (see TGA document).

TGA document
tga.gov.au/sites/default/…

In addition, a rational reason is required to change the full-length Spike to the fragment, but this would legally go against the "principle of good faith" and the "principle of estoppel," since BioNTech and the government officials have been alleged that the BNT162b2 is "safe and effective."

Therefore, they have faced with a dilemma in which they cannot solve the immune imprinting problem under the current platform BNT162b2.

In other words, the BNT162b2 has not only a platform problem of being unable to keep up with the viral mutation rate, but also a fatal problem of being unable to overcome the immune imprinting problem. The more BNT162b2 vaccinations given, the stronger the immune imprinting will be.

3/4

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Patent SUN

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May 16, 2024

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…

論文の補足資料を見ると、１日目～３５日目までのＣＯＶＩＤ－１９の感染死は０人でした。一方、３６日目～９２日目では１０人になっています。つまり、ワクチン接種者での感染死１名と、プラセボ接種者での感染死９名が３６日目～９２日目の間で発生したことになります。

デルタ株が流行していたようですが、１日目～３５日目までの感染死が０人である理由が、本当に０人であったのか、定義上の理由で０人であったのかまでは不明です。

論文補足資料
static-content.springer.com/esm/art%3A10.1…

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Patent SUN

@Patent_SUN

May 10, 2024

@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

The main points of this invention are extracted from the descriptions of the Claim section (Claims 1 to 3 are described here for convenience), and they are specifically as follows:

(A) This is a method of producing a composition comprising RNA having a reduced double-stranded (ds) RNA content.

(B) The starting concentration of UTP, or a functional analog thereof, is lower than the starting concentration of CTP and/or ATP, or a functional analog thereof.

(C) The method comprises supplementing the reaction mix during the course of the transcription reaction with a composition which comprises UTP, or a functional analog thereof, and is substantially free of CTP or ATP, or a functional analog thereof.

These points (A) to (C) are consistent with the disclosures in the EMA document. And these specific conditions are disclosed in the Table 5-1 of the patent which is identical to the Table S. 2.4-1 of the EMA document.

3/12

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Patent SUN

@Patent_SUN

Apr 30, 2024

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

@zombiemommy

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