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wow, some strong accusations being lobbed around here.
I know RECAF distinguishes between cancer cells... but I still thought this to be interesting as it looks at protein biomarkers:
Early Diagnosis Of Neurodegenerative Disease On The Horizon
08 Apr 2008
A new blood test that can give an early diagnosis of neurodegenerative disease and distinguish between Parkinson's and Alzheimer's disease could be launched this summer, reports Marina Murphy in SCI's Chemistry & Industry magazine.
Manufacturer, Oklahoma-based proteomics company, Power3 Medical Products, said it plans to sell the test, NuroPro, which would be the first diagnostic test for neurodegenerative diseases on the market, in Greece by Q3 with further plans for it to go on the US market by late Q3 or Q4."
"There is currently no diagnostic test for any neurodegenerative disease on the market - diagnoses are currently based solely on a clinical diagnosis of symptoms," said chief executive, Steve Rash.
Power3 has identified and patented several blood proteins(1) associated with neurodegenerative disease. The test NuroPro measures a suite of 59 protein biomarkers, the relative levels of which, they say, can help distinguish between Parkinson's, Alzheimer's and Lou Gehrig's disease or tell whether a patient is disease free. The test is highly accurate with a specificity and sensitivity in the high 90s, according to Rash.
Although the test has been welcomed by Kieran Breen, director of research at the Parkinson's Disease Society, as being particularly useful for monitoring the progression of disease and assessing the effectiveness of drugs, he urged caution saying: "While the test seems promising, larger studies need to be conducted before it can be confirmed as being helpful in making a diagnosis."
Susan Sorensen, head of research at the UK Alzheimer's Society said: "There are 700,000 people living with dementia in the UK, 62 per cent have Alzheimer's disease and this will rise to more than a million in less than 20 years. An effective blood test would present those diagnosed and their families with an opportunity to prepare for the impact of this devastating illness and make crucial decisions about their future.
"The method, known as proteomics, involves analysing proteins in the blood although it remains unclear which group of proteins gives the definitive signs of Alzheimer's disease… Some suggest Alzheimer's, for example, is too complex to be identified in this way."
Two clinical validation studies are currently underway at the Cleo Roberts Center of Clinical Research in Arizona, US, and the Research Institute of Thessaly in Greece.
The "cancer/protein" alert went off:
Molecule's 'Dark Side' Can Trigger Cancer
07 Apr 2008
Cancer Research UK scientists have discovered that a common molecule previously known to play a fundamental role in building protein, can also trigger cancer. The surprise findings are published in Cell*.
In previous work, the scientists based at Cancer Research UK's Beatson Institute in Glasgow, found levels of a molecule called tRNA**, which helps kickstart protein production, were unusually high in some cases of ovarian and cervical cancer.
So in the new study, researchers boosted ovarian cells in the laboratory with extra tRNA and discovered the cells turned cancerous. Three different types of fibroblast cells*** also responded in a similar way, leading the team to believe their research may be applicable to many different forms of the disease.
Lead researcher, Professor Robert White, from the Beatson Institute, said: "For the first time our study shows that tRNA, a molecule which has always been regarded by scientists to play a safe and rather boring 'housekeeping' role, can have a darker side.
"A great deal of our work has been based on understanding the changes that take place a lot earlier in the cancerous process to kick-start the damage. We can now see that tRNA also plays a fundamental part in doing this. This finding will open up new and potentially important avenues for drug development."
Dr Lesley Walker, Cancer Research UK's director of cancer information said: "This startling discovery raises serious questions about how important the tRNA will turn out to be in the complex chain of biological changes that cause cancer to develop. We now need to find out if the tRNA can be manipulated for the benefit of cancer patients."
*The paper, Elevated tRNAiMet Synthesis Can Drive Cell Proliferation and Oncogenic Transformation is published in the journal Cell on 4 April 2008
**tRNA or transfer RNA plays a fundamental role in protein synthesis (translation). Translation refers to the process by which a ribosome makes a protein based on an mRNA template (the messenger RNA sequence). There are different tRNAs, each one brings a specific amino acid (the building blocks of proteins) to the ribosome in the order specified by the mRNA.
***The cells used in this study were immortalised ovarian and fibroblast cells which have the capacity to grow in tissue culture and proliferate indefinitely mimicking changes that can lead to cancer.
The authors are Lynne Marshall, Niall Kenneth and Robert White from the Institute of Biomedical and Life Sciences, University of Glasgow, Scotland and the Beatson Institute for Cancer Research, Scotland
Professor White is running the Flora London Marathon for Cancer Research UK on 13 April 2008. You can support him through his justgiving page.
didn't know if this was ever posted, but an interesting article from 4/1/08:
Apr 1 2008 (Vol. 28, No. 7)
Revolutionizing Protein Expression in R&D Arena
Designing Better Systems to Energize Therapeutic Pipelines
Elizabeth Lipp
The expression of proteins for characterization, therapeutics, and diagnostics continues to be a challenging and complex task, requiring much time and untold expense. The payoffs, though, are well worth it. “Biomanufacturing is a multibillion dollar burgeoning industry,” noted Carlos Miguez, project leader, microbial and enzymatic technology group, National Research Council Biotechnology Research Institute in Canada. New data emerges every day that provides unique insights into methods for producing these proteins.
CHI’s “PepTalk 2008” conference in San Diego earlier this year explored challenges with protein expression, peptide and protein-based therapeutics, and mining the plasma proteome. Various solutions were offered for problems and bottlenecks.
Versabodies as Antibody Copycats
Antibody mimetics derived from nonhuman protein scaffolds offer an alternative to antibodies and small molecules. Volker Schellenberger, Ph.D., cofounder of Amunix, described his company’s microprotein-based Versabody™ platform and the philosophy that has driven it.
“Versabodies offer the superior affinity, specificity, half-life, and safety of whole antibodies combined with the superior stability, size, delivery, and nonimmunogenicity of microproteins. Since different targets have different requirements, format flexibility is critical,” Dr. Schellenberger added.
Amunix’ protocols utilize binding modules and spacer modules to create a variety of product formats that optimally fit each target’s biology. “The binding modules are microprotein domains of 20–35 AA including 2–4 disulfide bonds, which make them extremely stable and minimize immunogenicity.”
“A major limitation of many biopharmaceuticals is their short serum half-life requiring frequent injections,” Dr. Schellenberger continued. “Chemical PEGylation is frequently used to improve half-life and reduce protein immmunogenicity. However, PEGylation significantly complicates the manufacturing process and frequently results in difficult to separate and characterize mixtures.
“Amunix’ rPEG technology is based on protein sequences with PEG-like properties that are genetically fused to biopharmaceuticals, avoiding the extra chemical conjugation step. rPEGs have an increased hydrodynamic radius and show an apparent molecular weight that is about 15-fold their actual molecular weight, mimicking the way PEGylation achieves a long serum half-life.
“By alternating multiple microprotein domains with multiple rPEG linkers, we can create a single-protein product that has high potency due to multivalency and/or multispecificity, a long serum half-life, and is easy to manufacture in E. coli,” Dr. Schellenberger explained.
Versabodies are typically 20–60 kD and are expressed at high levels in soluble form in the E. coli cytoplasm. “The high disulfide density of microproteins makes our proteins extremely stable, enabling the use of differential heat-denaturation/precipitation as a one-step purification process,” he said.
To minimize the possibility of an immune response that cross reacts with native human proteins, Dr. Schellenberger reported that his group uses nonhuman microproteins. “Using directed evolution, we engineer the epitope content and protease sensitivity of these domains to minimize their immunogenicity.”
The resulting freedom to completely change the product’s amino acid sequence allows Amunix to optimize products for all desired properties such as stability, expression, formulation; whatever the therapeutic area calls for. “The product format is also designed to support optimal patent strategies,” Dr. Schellenberger concluded.
Novel E. coli Expression System
“You look at the number of microbial expression systems out there and wonder why there are so many of them,” Miguez pointed out. “The short answer to that is that, while an expression platform for protein x may work beautifully, when you move to protein y, it doesn’t work quite as well.”
Miguez and his group developed a gene-expression system for E. coli that could replace the IPTG-based platforms currently available. “The new system is capable of higher product yields compared to IPTG and uses p-cumate, a nontoxic, easy-to-handle, and cost-competitive inducer that can be used with popular strains of E. coli,” Miguez explained. “Applications include production of biopharmaceutical proteins, production of industrial enzymes, and basic and applied use in universities and research institutes.”
This E. coli gene-expression system is based on the regulatory elements of the Pseudomonas putida F1 cym and cmt operons to control target gene expression at the transcriptional level by using cumate as an inducer. It includes a specific expression vector, pNEW, that contains a partial T5 phage promoter fused to a repressor binding DNA fragment (operator) and the repressor gene cymR driven weakly by a kanamycin promoter PKm designed to express the repressor gene constitutively in the E. coli host strain.
“The exogenous inducer p-cumate is necessary for the induction of transcription,” Miguez explained. “The very tightly cumate-regulated expression system can be used with popular E. coli strains and potentially produce any gene that can be expressed using IPTG-inducible systems.”
Miguez noted that his E. coli gene-expression system is capable of high induction of transcription and low basal expression, surpassing the yields of IPTG-based gene expression systems. “The expression vector can be used with popular strains such as BL-21 (DE3), enabling those currently using IPTG-based systems to adopt the novel E. coli gene-expression system.”
One key feature Miguez commented on was that this expression vector is a viable alternative to ITPG-based systems that do not express some genes well, leading to insoluble or incorrectly folded proteins. Miguez’ E. coli gene-expression system may be an avenue for the production of these types of genes. “There is a lot of interest, and several companies want to try it out. Expression is gene dependent, which is why there are so many expression systems.”
Optimization in Baculoviral Expression System
Jim King, Ph.D., principal scientist for Boehringer-Ingleheim, and his group use the baculoviral expression system for optimization of proteins for crystallography. He calls this expression system the workhorse platform in both industry and academia for the last 15 years. “Until about five years ago,” Dr. King added, “it was really just a production system. In the last five years, it’s really advanced to screening a much larger number of constructs.”
Dr. King’s group has optimized and automated a high-throughput, small-scale baculoviral expression process to quickly and effectively assess protein expression. After one-step affinity purification, the resulting protein is analyzed using a Caliper Life Sciences’ LabChip 90 and is suitable for follow-up characterization to prioritize large-scale expression.
“We have applied this technique to many projects to scan domain boundary variants and point mutants. We actually do parallel small-scale screening, which allows us to use 96 constructs in parallel during one screen, and that screen takes about 10 days to get through all the steps. With the help of Caliper, we’ve created an automated system that does all the steps for us. The system is up and running, working out well, and performing exactly as we had hoped.”
The end game is to make systems easier to use and more accurate, making it easier for scientists to do their jobs, commented Professor Linda King, founder of Oxford Expression Technologies. “People who use high-throughput systems want them to be precise, so they can be used in conjunction with robotic technologies. Also, increasing the quality of the protein is key—as purity goes up, specific activity should also increase.”
Dr. King’s presentation highlighted recent advances in high-throughput, robotic technologies for the production of proteins in insect cells. The new advances include modifications to the baculovirus expression vector, flashBAC, to delete nonessential genes that result in enhanced yield and quality of many proteins. “The development of baculovirus-expression vector systems has accompanied a rapid expansion of our knowledge about the genes, their function, and regulation in insect cells,” said Dr. King.
Baculovirus gene expression occurs in an ordered cascade, regulated by early, late, and very late gene promoters. It has also been realized that the insect host cell has innate defenses against baculoviruses in the form of an apoptotic response to virus invasion. “Baculoviruses counter this by encoding apoptotic-suppressors, which also appear to have a role in determining the host range of the virus,” Dr. King stated. “Also of importance to our understanding of baculovirus expression systems is how the virus can accumulate mutations within genes that affect recombinant protein yield in cell culture.”
Protein Engineering for Diagnostics
“The work we do is not directly related to protein therapeutic applications, but we do research protein-expression technologies for diagnostic purposes,” stated Bob Wolfert, Ph.D., CSO for diaDexus. “What our team has done is optimize methods at high secretion rates. Our first product, the PLAC test, is a simple blood test that measures levels of an inflammatory enzyme that represents a new risk factor for coronary heart disease and stroke.”
Shaoqiu Zhuo, Ph.D., presented diaDexus’ work on the human embryo kidney-293 (HEK-293) cell line, which has been widely used to produce recombinant proteins. Many human proteins are cell-type dependent in expression and post-translational processing. “We have developed protein engineering methods for the expression and secretion of recombinant proteins in HEK-293 cells,” said Dr. Wolfert.
“One of the case studies we showed in the presentation is to enhance the expression and secretion of the mature macrophage inhibitory cytokine-1. We have identified one of the rate-limiting steps for the folding of the protein based on a novel glycosylation mechanism and are able to significantly increase the secretion of the mature dimeric form of the protein. This mutation and expression process can be easily adapted into 510K GMP production for our diagnostic products.”
Diagnostic kits for colon cancer, ovarian cancer, and breast cancer are currently in the works, added Dr. Wolfert. In creating immunoassay systems he emphasizes that he wants proteins that are native in structure yet amplified in nature. “We want to actually reflect proteins that are released in the blood stream.”
glad to see GS and Half-full Glass now part of the Moderator Team!
I hope we are paying those ~six employees more than $50K a year. You get what you pay for and I would think that BOCX would demand a certain skills set for performing/assisting with the lab work.
I guess it depends on what these half dozen people would be doing with job scope defined. ????
OT: This is pretty big news for those following therapeutics for liver cancer and metastic colorectal cancer... fresh off the press from over the weekend:
Tekmira Pharmaceuticals and Protiva Biotherapeutics Announce Business Combination to Create Global Leader in RNAi Delivery and Therapeutics
Sunday March 30, 6:20 pm ET
Alnylam and Roche to Invest $10 million in Combined Company
VANCOUVER, BRITISH COLUMBIA--(Marketwire - March 30, 2008) - Tekmira Pharmaceuticals Corporation ("Tekmira") (TSX:TKM - News) and Protiva Biotherapeutics Inc. announced today that they have signed a Share Purchase Agreement under which the two Vancouver-based companies will combine their businesses by Tekmira purchasing the outstanding equity of privately owned Protiva. The combined company, which will retain the name Tekmira, will be a global leader in the development of novel delivery technology and nucleic acid drugs, including RNA interference (RNAi) therapeutics.
As part of the transaction, Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY - News) and the Roche Venture Fund will each invest $5.0 million in Tekmira at a price of $2.40 per Tekmira share. At close, the new Tekmira is expected to have greater than $35 million in cash and equivalents.
The combined company will advance a pipeline of novel therapeutic products based on technologies and intellectual property contributed from both Tekmira and Protiva that covers a variety of lipid formulations for the delivery of nucleic acids. The new Tekmira will have rights to develop seven RNAi therapeutic products based on access to Alnylam's intellectual property. The new Tekmira expects to advance two systemic RNAi therapeutics into clinical development over the next 12-18 months as treatments for hypercholesterolemia and cancer.
In the field of RNAi therapeutics, the new Tekmira will have licensing and other relationships with Alnylam, Roche (SWX:ROG - News), Regulus Therapeutics, a joint venture between Alnylam and Isis Pharmaceuticals, Inc. (NASDAQ:ISIS - News) and Merck & Co., Inc. (NYSE:MRK - News). Each of these companies has licensed either Tekmira's or Protiva's technology and the combined company is eligible to receive milestone and royalty payments.
RNAi drugs have the potential to treat human diseases by "switching-off" genes that cause disease. The technology represents one of the most promising and rapidly advancing frontiers in biology and drug discovery - and was awarded the 2006 Nobel Prize for Physiology or Medicine.
The transaction, which has been unanimously approved by the Board of Directors of each of Protiva and Tekmira, will end all litigation between the two companies and their directors and officers. This includes all actions concerning contractual issues and rights to intellectual property surrounding the lipid delivery of siRNA.
you are not cautious... excuse me...
you are NOT cautious!!!! (almost forgot to use my !!!!)
You are just hoping to keep enthusiasm down so that you can buy some cheap shares and raise a bit more fear, uncertainty, and doubt (FUD) on this board.
As a cow is to cud, Dog is to FUD. Dog, your idiot quotient is on the upswing with every additional post.
thanks GS. I assume one has to be an iHub "member" in order to have an Ignore feature operable? Might be worth the money so I don't have to listen to the barkless dog.
guys, is there a way to mark the OT stuff in your very first sentence, so that it shows up "OT" in the subject line? It's really difficult for some of us to get through all of these messages in a short period of time. I am not shy about off-topic, but iHub doesn't appear to be very tolerant of it because there isn't the "OT" function so I try to respect that.
That is partly why I get crossways with Dog. I'm not interested in the trading banter and I really don't have time to read it. And when I quickly scan the board, I am likely to miss out on a noteworthy post. Whether Dog likes to stand on his doghouse or not, I could care less... I'm just trying to avoid the banter which doesn't pertain to BOCX.
thanks in advance
I am all for freedom of speech. I just find some of your trading commentary to be a bit of a distraction. I don't think I said anything about suppressing free speech. Add a few exclamation points (!), as you do, and it can be annoying. Like you, I'm entitled to my opinion.
Opp... did I read you right... Dog, strongly committed to this stock? Are you saying that in jest? He is trading this stock and filling the board with a bunch of woof woof commentary. I don't mind that he is straddling or strangling or swing trading, but I don't need the minute by minute commentary, and most of us are looking more long term view, and not as concerned about today or tomorrow's trading.
When someone appears to be rooting for a lower price per share to get back in and sell at a dime higher.... that is fine, but I don't need such commentary and I think it damages the intent of this board.
My apologies if I am misreading this situation.
I was not aware of Happy Hour. Thanks Gyro, for the tip!
to those of you sending me private mail... thanks, I enjoy it. But I don't have an iHub prescription, so I don't have the capability at present time to reply to your "private mail". This forum right here is "it" for now.
you got booted for stating a concern for the negativity? What? What is up with InvestorsHub? Am I next one to go because I'm questioning why this forum is behaving this way?
I have not seen anything inappropriate, and if anything iHub could use more posters... spreading the word. A boot on one's neck isn't exactly the best approach. Sounds like Half Full and Apollo have gotten a bit of a shaft. Who is this moderator?
I am not a "member" YET, but am certainly interested in the possibility.
By the way, a few of you have sent my private replies in my Mailbox and I am not able to reply because I'm not a "member", but I appreciate the notes sent to me.
Moderator, please address the concern we are having on this board... before it implodes. Can you please state the rules and policy on decorum? Thanks in advance.
I'm still hacked that Inverness never put out a dang presser talking up the BOCX license. That is thievery in my book. With partners like that, who needs enemies or short sellers??
GS, you mention bamboo as one of two who have visited BioCurex (from this board). Who is the other poster?
appreciable results from Terry? Surely you are kidding... I hope?
glad to hear that Terry got the axe. In a word, he STUNK when it came to investor relations or PR. My labrador could have done a better job.
whether Walt is too honest or not... in the CEO role, he is FAILING me, big time Walt. I have lost more money on this POS than I would care to admit. Unbelievable. I have been out of town, and came home to see this. This has totally wiped out my portfolio... I kid you not.
Walt is not my favorite guy right now. He is CEO and he is responsible for the PPS and should answer to the shareholder. This is a crime, I tell you.
If I could spit some nails out right now in this message, I would, but I am sure many others understand where I am coming from.
PETA would be all over this quick if dogs were tested with anything not yet declared dog-friendly. Only one way to find out. Dogs, primates, what's the difference?
wow, that's a lot of sheets which are pink!
Man, I wish that we weren't found by link to anything called "pink Sheets". I could do without that part of it. Yeah, I'm a stock snob.
I think that iBox or whatever it's called, will show up when you come to the board and you are NOT signed in. I had that same problem, but when you post, it makes you of course sign in.
That was the problem... I was sometimes needing to sign back in. Haven't seen the dreaded iBox since then.
got it... working! That is the first that I have seen of Walt, visually. Great! Thanks gents.
GettinThere... no link. We aren't "there" yet!
dick, link is not working. "page can't be found" is what I'm seeing. Could you post again, or paste it without hyperlink?
thanks
you should change your name to "opportunityknockout"! I agree with you. Valid concerns you raise. BOCX needs to take a lesson in shareholder relations 101.
Terry... do you also go by the nickname "Tex"? Just wondering.
if Dr. Moro has scored two touchdowns (nice analogy), then I would argue that Fox's cameramen went on strike during the game and the telecast has been interrupted, and nobody is seeing the game on TV.
if grandma is giving it till June, then I should give it till May! If any of us us sluggers sell our shares, the stock will likely drop fifteen cents in a matter of seconds.
Earth calling Terry and Wittenberg... get your azz in gear and start COMMUNICATING with your shareholders. When grandma puts up a deadline, that should tell you SOMETHING!!!!
oppknocking, I totally agree with you and share your frustration. It's like we are the ones charged with promoting this company, instead of BOCX management. If Terry reads this board, all I can say is that he should feel EMBARRASSED. This is a debacle and you are right on with your assessment, opp!
I agree, we're seeing incompetence... in the form of "aplenty". IMA hosed us completely with their non-announcement. BOCX has done us any favors either. Terry... can you do any worse than this?
agreed, Jag. By the way, I'm waiting for your further notice when cash is no longer king. Let me know when it becomes the court jester.
dick, as far as negotiations at a stand-still on acquisition, call me silly. I think that Walt's purpose would be better served if he didn't mention the potential acquisition targets in advance, during CC. Heck, those targeted people might have been listening to the CC, and heard a heightened interest... giving them reason to hold out for a higher sell price. I'm not an expert at what should or should not be divulged in these circumstances... but it would have served this shareholder's purpose better if he didn't mention it at all. I think that is why my shares have been pounded into the ground. And of course, the tax issue.
Dick, I did listen to the call a couple months ago in which two potential acquisitions were mentioned. Seems like he said that it would occur in Dec-Jan time frame for the two. I get the feeling that time is running out on the two targeted acq's.
what happens if Cabo gets struck by five hurricanes in the meantime, while we wait for approval? Sorry, couldn't help myself!
Dick, how much of a "small hit to earnings" for acquisition? We're already getting a merciless hit on the stock price, so can it get any worse than this?
Kag, those are my sentiments as well. And I made my feelings known to IMA's investor relations mgr by e-mail and never heard back from him. I'm ready to call him a slimeball for not giving me an honest answer as to why they won't put out a presser on their own web-site. Makes me tear my hair out!
Ted, that's my point. BOCX should negotiate these deals to take care of the long awaiting shareholder. You negotiate a deal in which Abbott or Inverness agree to put out a presser on their own. Can't that be arranged at the time of negotiation? Is that asking too much, I don't think...
Otherwise, it's a slap in the face to shareholders who still get nothing from Terry or anyone else... "but thanks for investing your money in BioCurex sir, and have a nice day". I don't think that is in our best interestf, me speaking on my behalf.
I don't know that we need an SEC investigation. I would settle for just a doggone press release from Abbott or Inverness!