HBV next HCV. More evidence that Big Pharma is believing the time has come to cure HBV comes in the form of patent application WO 2011/047312 by GlaxoSmithKline (GSK). Indeed, the intended mechanism of action of GSK’s curative concept is the same as for ARC520 by Arrowhead Research: knockdown of the viral transcripts, particularly HBsAg and HBeAg.
While the patent application merely sports early tissue culture data, what makes it worth a read is that it very nicely explains the HBsAg immune reactivation theory, including important references. Obviously, these guys are on the same wavelength as Arrowhead.
Explaining why gene knockdown may currently be the most promising approach. Highlighted is the 90% knockdown level, an indication of what type of activity Big Pharma is looking for when scouting for business development opportunities:
‘At the present time there are no effective therapeutic agents for treating humans infected with HBV infections which result in seroconverstion to the virus in the body, or which effect a 90% reduction of antigen…’
The clinical course of the disease shows correlation between antigen knockdown and functional cure:
‘Recent clinical research has found a correlation between seroconversion and reductions in HBaAg (Fried et al. 2008) and reductions in HBsAg (Moucari et al. 2009). Reductions in antigen levels may have allowed immunological control of HBV infection because high levels of antigens are thought to induce immunological tolerance.’
On the mechanism of the induction of immune tolerance by HBsAg, and again the 90% knockdown level:
‘HBsAg specific CD8 cells from CHB patients show altered tetramer binding. These CD8 cells are not anergic but may have TCR topology that confers partial tolerance or ignorance (Reignat et al. 2002). Moreover, reduction in serum HBsAg>1log at week 24 has a high predictive value (92%) for sustained virological response’.
On why a gene knockdown approach might allow for gentle seroconversion:
‘It is also expected that reduction of HBV antigen presentation in the liver wil help to minimize the extent of HBV flare-ups, a result of the immune system restoration, all of which will increase the chances of a complete cure of chronic HBV infection.’
GSK Partnered with LNA Antisense Company Santaris
In 2007, GSK, along with Sanofi and Merck probably the Big Pharm most active in oligonucleotide therapeutics, entered into a partnership with LNA antisense company Santaris for antiviral indications. It is therefore not surprising that the patent application describes and claims competing LNA antisense molecules, not RNAi triggers.
As you know, I greatly favor a DPC-based RNAi approach over LNAs both in terms of safety and potency. You therefore wonder whether it makes sense for GSK to invest in the clinical development of an LNA antisense compound in light of possible RNAi approaches and the HBV RNAi franchise by Arrowhead. GSK is no stranger to dumping LNAs/Santaris for other oligonucleotide options as they have done in the case of miR-122 inhibition for the treatment of HCV infection. In fact, it would surprise me if Santaris and GSK are having a good working relationship after that incident.
Whether GSK, Gilead or otherwise, it is clear that ARC520 is being closely watched by the industry. A 90% knockdown…a low bar for ARC520 IMO.
better more competition but this may force the companies to keep cronicity option live.because more companies succesful in hbsag clearance means less market share for each of them. to save their business they prefer to go for hbsag reduction option while keeping hvb cronicity live. that is what going on with arc 520 with so called confusing pseudo technical explanations. we have to keep the "critical technical eye" on these developements with the help of active participation of some of our best knowledgeable members in the field of biology. in our community, we have some sound academic people capable enough to analyse their data critically.
Applying your own logic, why would any experts help to provide critical eye, since helping to provide a solution would mean they have nothing else to do and would lose their jobs. I a m not a big fan of big pharma but to think that they would only provide a partial cure so as to maintain their market is too cynical. There are plenty of diseases out there, especial cancer and ageing, yes ageing can be considered a disease, for them to make money.
we must count the years the hep virus was discovered in 1967 and vaccine was in 1969 by Dr. Blumberg. what actually is done in hep b from then, almost nothing. so called major breakthroughs interferron was borrowed from hep c, tenofovir borrowed from from hiv community. actually no fundamental effort was done to undue cronocity of hep b.
46 years oh my god, think about it, don't you think if honest efforts were made did we need 46 years to reach where we are? no we didnt need and even today we are not sure weather it will need 5y 10 y 20 y or 30 y or never. no grand initiative from pharma or government or any fundamental research institutes. with so much breakthroughs in physics and technology they need 67 years to understand a dirty virus and still struggling. see the changes in world of technology over this 67 year period and you will find yourself angry with biologists, pharma and government. if they are honest there can be no hurdle in clearing after all it is just a chemical just a virus and immune system has enough power to kill this just a trigger is needed.
typo not 67 years, it is only 46 years after discovery of this "very very very ultra super super most strong virus of universe". beacuse only this much strong virus could need 46 years to get understood, still not fully. too funny dears its too much funny.
in future, never tell an alien about this, they will laugh on us, on our whole human race and its social values.
So you are now suggesting:
1. scientists are stupid, or they are not making an honest effort;
2. big pharmas have cures for hbv, but they are sitting on them because they want to make profit forever;
You are venting your frustrations on and blaming others.
Some governments may be ignoring hbv, but ultimately what have you done, and what are you going to do?
sorry if u were disturbed.
1. there may be brilliant scientist but the progess made in 46 y suggests there must be something wrong which is blocking the fundamental hep b research.
2.if big pharma decides and tries, they can have cures, but they donot want the cures.
yes most of us have frustation for not getting cures but with nucs, may be u have not frustation, its good.
not some but most of governments are ignorant. being responsible doesnot mean distribute nucs freely to naives. responsible means making fundamental and sustained efforts to make situation better. celebrating hep b day with cake and burger and donating dollers is not going to help a lot anyway.
they didnot ask me,my dollers and hard work to win the moon (APPOLO). Actually why dont u understand my dear hep b needs intence government interference and political motivation like appolo mission. for that we have to raise the voice.thats the only thing raise your voice wherever u can.and I m raising it. U could too,but your wish.
see this another example of big pharma culture (though from hep c, this was status in feb13 , i dnt know about their current status and policies.):
At a recent national medical meeting of liver specialists, Dr. Mark Sulkowski of Johns Hopkins University Medical Center described a Phase II research protocol using a combination of two new oral medications, daclatasvir and sofosbuvir. This medication combination has almost no side effects.
The gist of Dr. Sulkowski’s presentation is this: After a mere 12 weeks of treatment with this new regimen, the “cure” (SVR) rate for hepatitis C was an astonishing 93 percent.
Hepatitis C patients have been waiting for a treatment regimen like daclatasvir and sofosbuvir for decades. It’s a true rarity in medicine — an honest-to-goodness game-changer, a phenomenally effective regimen for a serious, life-threatening disease that is also safe and well-tolerated.
The only problem? The two drugs are owned by different companies — daclatasvir is a Bristol-Myers-Squibb drug, while sofosbuvir is made by Gilead Sciences.
For reasons that are almost certainly financial in nature, Gilead has refused to do further work on this drug combination with Bristol-Myers Squibb, so there will be no further study of the regimen. With no Phase III trials, that means that the daclatasvir/sofosbuvir combination regimen will likely not be approved for use by the FDA.
You bet I am disturbed by your frequent but unsubstantiated claims that there are already "cures" for hbv. They are dishonest claims, a useless distraction and do nothing for hbvers.
As for the combination of daclatasvir and sofosbuvir, ask yourself this question - if you are so sure that the combination will cure, why the need to do a clinical trial? Why don't you just take the two pills yourself?
Be honest, you are not raising your voice to tell your government, the scientific community, and pharma to do more, you are accusing them of being in a conspiracy to deny you a cure that they are able to deliver to you yesterday.
one thing i want to correct you is, i m not saying they have cures. i m saying they can have cures but they are not motivated for finding a cure.
what i did is much better than claiming and a selling fraud cure and sitting dull with keep saying others that please dont do anything, it is not fruitfull. please dont do anything, every thing is perfect and its gods wish.
atleast by putting my point, which many other members also worry about, everybody in this forum is now aware of possible current situations in pharma. you may be good expert of outside real world, so better to fight with the real world than me.i m already fighting with hep b.thanks.
Why should they be motivated to finding a cure for you? It is not their illness but it is their money. So what have you done to finding a cure? All you do is to malign the very group of people, the scientists and pharma who are in a position to help, that they are incompetent and not motivated.
In this forum, we are here to share knowledge and experience, to help and support each other. Now and then, we also raise hope by passing on news about encouraging new scientific and medical developments. What we don't do is to say, hey, there are cures out there but the scientists and pharma are just not interested.
Let me tell you something. Yes I believe they have a way to irradicate the Hep B virus. But absolutely no interest in distrubuting it!! I seen a a journal bought out by http://www.tum.de/ but after me contacting them I noticed they took it down . (Guess the poor bugger who's suffering shouldn't be watching these kind of things.)
It was saying they could irradicate this virus via the immune system. If I recall they mention it was shown to be far more affective than viral inhibitors. When I contacted the scientist/immunologist who wrote and made this discovery they had absolutely no interest in talking to me even though I live with this & I was told it might not ever get onto the markets. Hope smahed to bits. Stephen Castlecrag I believe being very naive if you believe the love of money doesn't rule everything in the world of the big pharma's. research bias very prevalent according to this md here's the link .
Glaxo? Trust Worthy? Ask the Chinese. This laughable. OOOHHH they got a patent? Patent=CASH AND LOTS OF IT!!!!
Screw this system I wouldn't take anything they offer just because I know they don't really give a damn in my view the majority of scientist are more concerned about getting their name on credits rather than doing whats good for man kind. I'm just looking forward to death at least I won't have to deal with a mashed up liver. Newtr you are being helpful and I fully support what your claims are so far as I haven't had a chance to read the rest yet. StephenCastlecrag I find your comments dis-empowering sounds like you work for the pharma's or had a good brain washing from them!!
If I find something I will happily share it with the world.
But the links I posted explaining my point have been taken out.
I don't want to sound like I'm just ranting. I'm just so frustrated at my whole experience sorry if I've sounded harsh but its no joke living with this. I'll copy and paste the journal here tommorrow as I think its on my other hard drive so it'll have to wait until tommorrow
I only have real faith in countries that are really affected by hepb , think of china taiwan , they treat hepb as a social problem rather than a way make money . Im also a little little bit hopeful in ARC 520 , because when the hepatitis b gets supressed far enough , the immumesystem can gain the upperhand and wipe it out . They should nationalize big pharma and make it goverment run solely for the purpouse to cure every disease thats out there , but then they will be losing the tax money they get from the profits of big pharma
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