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if you also read page 9 it gives you the indication that Scancell was surprised just how immunogenic the peptide was hence the peptide vaccine was only needed ...........
the reason why i giving you guys this info ... is risk ...
scancell did not need to add the potency of Immunobody .......... to what is a potent peptide vaccine ... with just the peptides alone, adding the adjuvant by conjugated technology changes the polarisation to TH1 ... it does not add high avidity but high inflammatory ... remember they are still helper t cells that also can kill...
which is why i ask folks to think ......... and not just follow this is all to risky route like Ruck and Burble followed
i
In January 2020, the average P/E ration for US biotech companies was 77... just saying.
Max i can take the thread aware .. you know i can .. but concentrate on the end game ... not the few pennies fluctuating in between
Moditope is HUGE ....
Morning LL,
Of course you allowed to change your mind.In fact to me it is a sensible course of action if circumstances change or news arrives. However some have such a fixed conviction positive and negative that does not allow for anyone to change their thinking.This intolerance and the need to be always right invariably means that debate is not allowed to flourish and when the SP falls it only heightens these tensions.
So stay polite and don’t worry too much about the discourse and be happy.
Inan,
Firstly, as with all inventions an inventor will patent not just the invention specifically but also a wider patent space surrounding your invention.
through this you see a range of thing and I’ll break them down for the rest of the readers to understand:
The patent covers a broad range of epitopes from different proteins including NYESO, Cytokeratin, HSP90, BiP, ING4, CXCL10 and CXCL12 as well as vimentin (the main focus).
Clause 12 – lists the epitopes the patent covers, then details which arginine residues are modified (citruillinated). Then finishes with the preferred vimentin residue.
Clause 13 – highlights the preferred citrullinated epitope from vimentin and that it can be used to raise an immune response to a range of cancers but not limited to just those listed.
Clause 14 – Goes into further detail regarding the preference for which one, two or three arginines are citrullinated and also says that additional residues can flank the epitope.
Clause 15 – Highlights alternative preferred epitopes of vimentin and then details which of the arginines within these should be citrullinated.
Clause 16 – Highlights further epitopes from vimentin that are also included within this patent and highlights the arginines which could be citrullinated. Note however, that they have not specified which ones are preferred (e.g. these could be moditope targets, but they haven’t done any/limited work on the immunogenicity of these, so have included them in the patent just in case’.
Clause 17 and 18 are an interesting one. You’ll note that these specify the same epitopes that were listed in clause 14 and 15, but this time without mentioning the citrullination however these clauses do include the sentence ‘and/or a nucleic acid encoding such an epitope, for use in a method of treating cancer.’
Now why would they include the same clause twice?
The answer is because they are patenting the preferred epitopes without the citrullination modification in both peptide and DNA form. As I said in my earlier post you can’t encode the post translational modification in a DNA vaccine – that statement still stands.
As Moditope (in thise case I’m talking about modi-1) specifically relates to citrullinated vimentin and alpha-enolase proteins. Your statement saying ‘moditope was inserted into a DNA construct using whole length vimentin’ is incorrect. You would be correct though in saying unmodified vimentin (peptides or full length protein) or specific ‘pre-moditope epitopes) are able to be inserted into a DNA construct – that is true. But to call that moditope would be factually incorrect because moditope specifically refers to the citrullinated form or stress-induced post-translational modified (siPTM) peptide form.
1/2
2/2/end
For citrullination to occur, you need cell-stress to occur (e.g. be hypoxic, nutrient deficient or be in some form of oxidative stress). Therefore the only way you would be able to obtain citrullinate ‘moditope’ peptides in vivo using a DNA vaccine would be to have a way to target the DNA vaccine to a stressed cell, express these peptides (as unmodified amino acid sequences) AND then expect it to be modified – something you have no guarantee of happening.
Taking the above into account. If you use the term Moditope you are specifically talking about a siPTM modified peptide. You cannot encode a siPTM peptide into a DNA vaccine, hence Moditope is not able to be delivered as DNA based vaccine. You can however deliver pre-cursor peptides in a DNA based format, but you are then expecting it to be modified in vivo – something you have limited control over.
Excellent post Burble
Great having someone who understands the science and the platforms. A welcome addition to the board.
Again in need of correction Mr K - 'you spent hours crawling through all my old posts trying to find something' - not true, it was the work of minutes, and careful research is always a good way to find the truth.
'anything that might discredit me' - it was what you wrote, verbatim.
'I am living in your head rent free' - also untrue. Maybe doing a guest comedy act now and again, but certainly not resident there. However it does seem to be exacting a toll on you.
Now run along there's a good chap, Headmaster will be out soon if you don't settle.
Not a problem in the slightest! Please do ask is there is anything you don't understand. At times, I do find myself flipping into scientific terminology, even when trying to write a lay response.
mmm.. so we didn't need to split the patent ... for nucleic acids then ...
anyway easy way to solve the issue ............. ask the Boss . so I have
and there is the answer exceptionally quick
""It works with Immunobody ""
Lindy
i will forward the email to Bunsie
Thanks Burble,
This is really refreshing and informative.I really appreciate that you are writing the posts using your everyday language and in an original form in which your sincerity and knowledge comes to the fore.
This is important to me in that I can just take it as read and challenge/ ask for clarification if I felt the need to do so but as usual always prepared to accept an expert opinion if I feel they have no axe to grind.
Lindy is the Expert and does not have an axe to grind ................
LL,
I’ve been tied up with Loads of family stuff today So only just seen your post..
“ I'm curious though as to what you use to keep track of all the conversations. Surely you don't waste all your time trawling back through the feed. ”
Those of us who have been here a while have realised that Inan catalogues every post, indexing it poster, date, prevailing share price, thread ID and assigning each one a score on the rampometer and drivelometer. He can then access any post instantly using various search criteria.
yea ... mentally ..
hence i catch you out so often ....
like "i won't buy any more" ... then "sold some to buy back" .... holding back the bazooka ............ £500
Inan,
Many thanks for the email, very informative and confirms what you have been saying all along IMO
Just goes to show who the Trolls are doesn't it, just look for the "B--wn Nosers" through this thread!
ATB
Bunsie
yep ........... i think Bermuda finally got clear of Ivy and Ruck ........... well done him .. looks like they have tagged burble poor man .......... by the time they have finished he will be collecting the Noble prize not lindy
like i said ......... many do not understand what Burble is posting anyway .. even in laymans terms so it makes little difference
that is why they did not pick up on the relevance of Car T and Risk ...
its a BB for investors ........... Science Light
'Its a BB for investors ........... Science light'
But without the science and a full understanding of the science, people cannot fully comprehend risk/reward. They cannot understand the potential for success, equally they cannot understand the potential for failure. The latter could be a technical failure (it doesn't work as we expected) or a market failure (e.g. there are others in the same market which do the job better, cheaper, safer, quicker etc).
'Many do not understand what Burble is posting anyway .. even in laymans terms so it makes little difference'. Maybe so, it is highly likely that many people do not understand what I am saying. We all know many people invest with zero understanding of what they are investing in - that's not my problem.
What I will say though is if a single person understands the science that SCLP are doing a bit better than they would have without reading my or any other person on this boards posts, then the SCLP bulletin board will have been a success.
I'm not out to make personal attacks on people or play dirty. What I will do however, is continue to challenge posts I feel may need further questions asked about them, I will continue to ask questions of the points that I myself do not understand, I will continue to reflect on others posts and also question my own understanding of the science behind SCLP. I hope others will do the same. A bulletin board inherently is for everyone to read, to post, to understand, to question and to digest information. It's not a place for infighting. Life is too short for that.
well it don't matter does it ... if pretty well every post you make is wrong .....
example you said Mab 2811 could cause cancer ...
I'm really sorry to ask this, but does the recent set of posts with the input from LD mean that Inanaco knows more about the science than Burble?
I don't claim that ......... i am sure if Burble researches he will out perform me by a mile ....... but making statements based on what you think you know as definitive is not the route
I would like to think that I have acted with humility (and I offer anybody the right to tell me if that isn't the case). If I am wrong and someone has corrected me then great - it's all part of being a scientist.
We make assumptions based on the data we have in front of us. When someone comes along and presents conflicting evidence, we weight it up against what we know and then decide whether it challenges our own assumptions of the subject. The same goes for when somebody presents supporting information. The great thing with science is that it is not just black or white, it has many shades of grey....but fundamentally we don't know how many.
Something that we believe is fact and has been for many years, may change. Someone will come along and present a whiter white, or a blacker black. That doesn't change the knowledge or results in front of us, it just changes the context. The shade of grey, has suddenly become slightly closer to black than we thought it was or slightly closer to white than we thought it was. Fundamentally the shade hasn't changed. This is what's so fun about science, it's never ending.
The reason I am saying things like 'have we considered whether Mab 2811 could cause cancer', is because it's me trying to contextualise data put in front of me and highlight that there is always a risk that this could happen. It's not me stating that is *is* going to happen, it's me stating that based on the evidence in front of us that is a *potential* risk.
Science demonstrate that T memory stem cells have the potential to be harnessed for use in T-cell based therapies against cancer and infectious disease (white). It also demonstrates that TSCMs play a role in autoimmunity, T-cell leukaemia and T-cell based infections (HIV etc) (black). Hence, my question could be posed in a different way.
Based on the limited data we have on Mab 2811, it's effects can be placed somewhere along that gradient from black to white. At the moment, it could be closer towards white (good end). It might also have the potential to move towards black (bad end). Until we have further data on it, on its effects and on long term effects in vivo using it, we just don't know where on this spectrum it lies. Rather than looking at it through the eyes of the ever optimise 'this will only ever go towards white' we should think of it more through the eyes of a realist 'it has every potential to go either way'.