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HISC have anything that might fit this request?
http://www.utekcorp.com/technologies/TSR_CCH_080406.pdf
Later,
W2P
I'm curious to know whether it is legal or ethical for a patent attorney to use his professional access to patent office documents prior to their being made public, and to disseminate that information to select individuals.
Anybody care to comment?
Thanks,
W2P
gunnabe...According to the article, Gabriel still lives in Boston. I know that Handelin WAS in Pennsylvania...I justed assumed Handelin was the PA employee.
Don't really understand everything it takes to develop a computational biology program, but would have to believe that a good portion of the work could be done at a remote location given today's communications technology.
BTW, can't access either site.
Last, did you note Gomez's comment that annual revenues are in the $3 million range? Revenues thru three quarters were approximately $1.9 million. Bit of a stretch, but from these numbers it appears they had a decent 4th Quarter.
Later,
W2P
chiggah...This is my favorite line:
http://www.bradenton.com/mld/bradenton/business/16502822.htm
...Both Gomez and DNAPrint Genomics will also be part of a massive research initiative announced last month by the H. Lee Moffitt Cancer Center & Research Institute of Tampa. The center said it would partner with an affiliate of Merck & Co., Inc. pharmaceutical company to expand biotechnology research with the goal of developing personalized medicine...
Later,
W2P
gunnabe...I believe that Barbara Handelin lives in Pennsylvania. I have the same question about Colorado though...
Later,
W2P
Don't know if this is known or not, but Telkonet received notice of patent allowance on 11/09/2006, with formal Issue Notification on 01/10/2007 from the US Patent Office for:
Method and Apparatus for Attaching Power Line Communications to Customer Premises
iHub won't post the url correctly...but you can find it at:
http://www.uspto.gov/
Left Menu:
Select "View In Pair"
Scroll Down to View:
Select "Public Pair"
On "Select Search Method" drop down and Select "Publication Number"
On "Enter Number" enter: 2004-0196144
Later,
W2P
gunnabe...I believe that this statement from the PR may garner more interest once the article is published:
...This observation indicates that the genetic marker may be related not only to response to statins but also to a possible relationship with higher cholesterol levels, according to the study.
Knowing the way the press works in this country, any study conclusions related to the marker's ability to infer higher cholesterol levels may get as much or more press than the findings related to myalgia.
All in MHO, of course.
Later,
W2P
Bag8ger, gunnabe, Virgil...A commendable effort, however, if frog were really interested in the truth of the matter, he/she would have read the Patent Application by now. Clearly, he/she hasn't.
I also fully recognize that he/she is either unwilling or unable to understand/acknowledge the text that follows, but for the benefit of the intelligent and/or interested readers I offer the following FROM THE PATENT APPLICATION:
...the results demonstrated that a Lipitor® patient could be classified into the non-adverse response (muscle reaction) group with 96% accuracy, and that 98% of the cases (individuals who exhibited muscle reactions) were properly classified.
The statistical conclusion from the above text is that errors in the classifer fall on the side of placing some non-adverse responders into the adverse responder group. This would certainly not be unexpected since the vast majority of statin users, 95%, are non-adverse responders to begin with. But by the same token, fully 98% of the cases, those individuals who exhibited muscle reactions, were properly classified.
Using the example you have been discussing, this means that while a small number of individuals will incorrectly be told they are at risk of developing myalgia and be placed into the adverse responder class, only 1 of the fifty patients that IS predisposed to develop myalgia would have been placed in the non-adverse response group. In other words, by using the classifier to "identify" the adverse responders, the rate of myalgia incidence could be reduced from 50 in 1000 to 1 in 1000.
Since the goal of a classifier is to prevent adverse reactions, I am hard pressed to understand how this classifier would not be useful to a physician trying to protect his patients.
And as far as the "straw man" frog is attempting to establish by making a company PR the definitive, end-all piece of information (and mistating the contents on top of it) versus either the Patent Application itself OR the JPG Article, I would simply point out that the information in the PR is, necessarily, a "subset" of the information contained in the Patent Application and Article, not the other way around.
frog...try to understand the difference between a public relations piece, a patent application, and a scientific study and resulting paper. Quite simply, out of the three, the PR will always contain the least information. Why is that so difficult for you to comprehend?
As always, this is MHO. Do your own DD and make your own investment decisions.
Later,
W2P
Appears as if there has been progress on the AIM patent application.
Follow the link below and read page 4 of the "Examiner Interview Summary Record from the 12/18/2006 phone interview with the Examiner and her supervisor:
http://portal.uspto.gov/external/portal/!ut/p/_s.7_0_A/7_0_CH/.cmd/ad/.ar/sa.getBib/.ps/N/.c/6_0_69/....
The patent attorneys also submitted revised claims and arguments meant to address the issues discussed during the phone interview. See the "Applicant Arguments/Remarks Made in an Amendment" submitted 12/26/2006.
Looks to me like this is coming to a head. But of course, that is JMHO. Do your own DD and always make your own investment decisions.
Later,
W2P
sirius...Relax...Did you give gifts in December 2006?
The Form 4 is quite simply a legal document designed to allow transparency to ALL shareholders as to what insiders are doing with their shares. The "D" has nothing to do with selling. It simply means that they no longer are the legal owners of the shares.
If you had to report on every one of your personal financial transactions, anything you gifted to anyone would be designated with a "D". Anything you received from anyone would be designated with an "A". But just as "A" doesn't necessarily mean you "bought" something, "D" doesn't necessarily mean anything was sold.
These are simply gifts. Could be to family members, could be to charities (many give shares of appreciated stock to their church, it's a tax efficient method of giving), etc. IMO, this is absolutely nothing to be concerned with.
Later,
W2P
The marker referred to in the PR IS the marker identified in the patent. Specifically, it is:
[0141] More specifically, these studies showed an association between myalgia and one particular CYP2D6 poor metabolizer allele, the CYP2D6*4, rather than a more generalized "poor metabolizer" status. For example, no associations were found between myalgia response and CYP2D6 poor metabolizer alleles other than the CYP2D6*4 allele.
The results were confirmed using a second (though relatively small set) of blind validation samples. The specific conclusions were as follows:
[0146] Overall, and in summary, these results clearly show:
1. The claimed CYP2D6 marker 179-172 alleles are linked completely with and therefore part of the well-known CYP2D6*4 haplotype.
2. That the claimed CYP2D6 marker 179-172 alleles equivalent to the well-known CYP2D6*4 haplotype were highly associated with atorvastatin-induced myalgia in a first set of 75 samples.
3. That the claimed CYP2D6 marker 179-172 alleles equivalent to the well-known CYP2D6*4 haplotype were also highly associated with atorvastatin induced myalgia in a second set of 64 validation samples.
4. Therefore, the claimed CYP2D6 marker 179-172 alleles equivalent to the well-known CYP2D6*4 haplotype constitute a validated risk factor for atorvastatin induced myalgia.
This is not "old" news as you continuously assert. While it's original US filing date is December of 2004, this patent application was just published Internationally in May of 2006. To my knowledge, the company has NEVER announced the existence of these associations publicly, save the abstract presented last March in Baltimore.
The significance of this PR at this time is that the science described in that patent application has been validated in a 750 patient study, and the results have survived the "peer review" process. Surely you know the importance of peer review.
As to your continued mistatement and apparent misunderstanding of the statistics and accuracy of the classifier, it would take far too long to address in detail. But generally, you are attempting to apply the statistical evidence of association (as described in the PR) to the level of accuracy acheivable in the completed classifier. The only thing you seem to understand correctly is that they are NOT the same thing.
As I have stated in past posts, the classifier WILL NOT rely on that marker alone. That marker constitutes a penetrant response related marker. There is at least one other (highly relevant) penetrant marker identified in the patent that is protective. In other words, it's existence is highly indicative of normal (non-myalgia) response. In addition, there are a number of latent response related markers whose presence or absence improves the classifer accuracy.
Here is the summary from the patent that describes some of these additional markers and their relevance:
D. CLASSIFICATION ACCURACY WITHIN DISCOVERY SET
[0154] The results described above demonstrate that alleles of two separate Cytochrome P450 genes are associated with atorvastatin-induced myalgia response. The following conclusion can be drawn from the data presented above:
1) The CYP2D6 gene, where the CYP2D6*4 allele marked by the CYP2D6 179-172 TT-TC or TC-TC genotype pair, or directly with a CYP2D6*4 genotyping assay, is indicative of likelihood to express atorvastatin induced myalgia
2) The CYP2D6*10 allele marked by the 179-172 CC-TC genotype pair, or directly with a CYP2D6*10 genotyping assay, is indicative of likelihood to express normal (non-myalgia) response to atorvastatin.
3) Certain CYP2C8 haplotypes as discussed above, are indicative for myalgia or normal response to atorvastatin.
4) Native American and East Asian admixture as discussed above are indicative for myalgia or normal response to atorvastatin.
[0155] A simple classification can be used to combine the CYP2D6 and CYP2C8 risk alleles into a scheme, where possession of a "risk allele" or "factor" can be used to infer the classification as a myalgia responder, and possession of a "protective allele" or "factor" can be used to infer the classification as a normal responder, and lack of a "risk" or "protective" allele or factor bestows upon the individual an inconclusive classification...(Table 19 is not shown in the document)
[0156] As shown in Table 19, approximately 2/3rds of the patients carried a risk or protective allele and could therefore be classified; of these, 97% were correctly classified using the above classification scheme.
Understand that Paragraph [0156] provides an example of a "simple" classification scheme. Table 3, referred to in my original post on this subject and questioned in your post, shows the results of a "complex" classifer. I don't know, and obviously, you don't know what the final marketed version will be able to achieve.
But the ONE thing that appears evident is that DNAPrint IS moving forward with their original research...which if I'm not mistaken would make these statements...
Haven't you wondered why DNAG has given up on its SNP based agenda?...
We can certainly watch the latest programs unfold, but you can rest assured that SNP based 'personalized medicine' is a thing of the past...
Not to mention the six years wasted on DNAG, who will apparently have no part to play in the eventual triumphs of personalized medicine...
The old paradigm that assumed that all of the diversity in the genome was haplotype based and thus amenable to SNP based diagnostics is, in fact dead. My earlier posts that 'conveyed' (Your word) that DNAG's SNP maps were no longer viable were intended to say exactly that. DNAG's exclusively SNP based maps and classifiers are useless...
The 'reason' that DNAG's SNP maps are useless, while SNPs themselves maintain their value, is the underlying assumptions that have changed...
This new understanding not only explains the difficulties experienced by DNAG with their 'nomes', it renders the entire approach obsolete...
Wrong...
The opinions expressed in this post are my own. The information and data is excerpted from publicly available information. Please make your own investment decisions based on your own due diligence.
Merry Christmas,
W2P
Technically, in the year 2000 they started the project looking to classify responders vs non-responders (efficacy of response) AND to produce methods capable of inferring a patient's susceptibility to an ADR. The original patent filed in 2002 covers methods to classify efficacy of the drug in patients and infer hepatocellular damage.
Both the Myalgia and negative response to ACE Inhibitors came later. They were the subjects of a new patent filed with the U.S. Patent Office on November 12, 2004. That patent was filed Internationally on November 2, 2005.
As I've already posted, their 10KSB filed on 3/29/06 tells us that:
http://www.sec.gov/Archives/edgar/data/1127354/000123174206000203/dnag10ksb.htm
Statinome: During 2005, we began a study with Genomics Collaborative Division of Seracare Life Sciences Inc. that also included the statinome program. Samples have been received from them and used to conduct a validation of the test. An abstract was presented at the last meeting of the American Society of Clinical Pharmacology and Therapeutics (March, 10, 2006 in Baltimore). Also, a paper has been prepared and submitted for publication.
I don't think it takes a rocket scientist to figure out that the upcoming JPG article is the article referred to above (You DO realize that the Peer Review process takes months, right?). The article would have been written AFTER completing the validation study, and the validation study would have taken place AFTER the discovery. Now since the validation study took place in 2005, I think it's safe to say that the discovery was actually made PRIOR to 2005, and would quite plausibly, if not undoubtedly be the subject of that November 2004 patent, which was quite probably updated with the validation data when it was filed internationally in November 2005.
Now, are you keeping up with me or do I need to go a l i t t l e s l o w e r...
Later,
W2P
I know you are the master of minutia, but I suggest it is you that needs to reread the PR:
The marker was the primary discovery from the Company's Statnome project initiated in 2000 and the manuscript to be published in JPG describes the validation of this finding in different patient samples.
The clear implication is that the discovery came from the original Statnome project...old, not recent, thus the marker "was" the primary discovery...the completion of the validation study is the recent event.
"This is the culmination of a project that was begun when the company was founded," stated DNAPrint President and Chief Executive Officer Richard Gabriel. "It has taken until now to validate the original findings, but validated they are.
Now, you aren't REALLY suggesting that they discovered this variant and proceeded to conduct a validation study without FIRST filing a patent on the discovery are you? And just so we're clear here, you DO need to first discover it prior to conducting the validation study. How long after the discovery do you suppose they filed the patent? How long after filing the patent do you suppose they organized the validation study?
Let's see, according to you the patent was filed two years ago - 2004? Doh...what have we here from one of the DNAPrint quarterly reports:
Statinome: During 2005, we began a study with Genomics Collaborative Division of Seracare Life Sciences Inc. that also included the statinome program. Samples have been received from them and used to conduct a validation of the test. An abstract was presented at the last meeting of the American Society of Clinical Pharmacology and Therapeutics (March, 10, 2006 in Baltimore). Also, a paper has been prepared and submitted for publication.
Tell me Mr. Strawman...the timeframe looks pretty plausible to me...what do YOU think? Let's see, they just received the "validation" samples in 2005. They first presented the validation results as part of an abstract back on March 10, 2006. Why, that would probably mean the "discovery" was made and a patent filed PRIOR to 2005, wouldn't you say? 2004 perhaps?
As far as our "brief" exchange last week, you need to understand that I don't live here like you and your buddies do. I have no interest in getting involved in one of your circular semantic exercises. If you'd like to deny that the clear implication in your messages leading up to my post was that DNAPrint's tests were useless because SNP's were being relegated to history then all I can say is...Aunt Jemima your waffles are done. I could post message after message of yours containing that clear implication and you know full well that that was the subject of my response.
If you insist on a contention that a short statement in my quickly written post to Bag8ger was the crux of our discussion then let's just end that here as well. Let's see, you took a short segment of the post, separated it from the context of the message and claimed that to be "specifically what this dicussion was about". First of all, I didn't say "ALL" CNV's as your followup claims. I used the word identify, as in the ability to isolate as opposed to "discover". In order to do large scale research a geneticist needs a means of identifying the CNV's in multiple samples in an efficient way. The point was that they are an invaluable element in genetic research, and that one of the key benefits of using the Affymetrix Mapping Array was the resolution and ability to isolate the boundaries of the CNV's using SNP based technology. A point VERY clearly substantiated by the words of one of the lead researchers in my followup post.
Now, if you'd like to discuss why DNAPrint's classifiers are NOT greatly impacted by the Nature Discovery I'd be happy to discuss it. But you have to cut your usual "bull" because I don't intend nor do I have the time to hang out here all day and play. And I can't promise that responses will be posted within hours or even days. I have a life...unlike some here.
Later,
W2P
And it appears as if you'd be wrong, as usual, again...LOL I think you'll find that the patent itself includes the classifier as well as methods for using the single genetic variant; and that the classifier version, by incorporating additional variants, is capable of identifying with 96% accuracy those likely to suffer adverse muscle response. This from the Description of the Invention:
[0006] Accordingly, in one embodiment, the present invention relates to a method for inferring a muscle adverse effect statin response of a human subject from a nucleic acid sample of the subject. Such a method can be performed, for example, by identifying, in a nucleic acid sample from the subject, a nucleotide occurrence of at least one statin response-related SNP of a marker as set forth in any of Tables 1, 2, 4, 5, or a combination thereof, whereby the nucleotide occurrence is associated with a muscle adverse effect in response to administration of the statin, thereby inferring the muscle adverse effect statin response of the subject...
My impression is that the followup study they refer to in the PR was conducted to confirm their ability to infer response from a single key biomarker. It doesn't necessarily follow, however, that a classifier could not further refine the sensitivity of the test or that the single variant wouldn't be incorporated into a broader, more sensitive test. Indeed, according to the patent we have the following:
[0115] The SNPs identified above were used to make classifications of patients receiving Lipitor®. Genotypes were determined from a sample (e.g. blood) from patients suffering muscle adverse effects (case) and from patients not suffering muscle adverse effects (controls). Genotypes were selected for which the prevalence between cases and controls was more extreme than 63%:37%, or 37%:63% (giving a risk of non-response in terms of classification theory of about 3). As shown in Table 3, the results demonstrated that a Lipitor® patient could be classified into the non-adverse response (muscle reaction) group with 96% accuracy, and that 98% of the cases (individuals who exhibited muscle reactions) were properly classified...
For anyone interested, this would appear to be the patent in question:
(WO/2006/053322) COMPOSITIONS AND METHODS FOR INFERRING AN ADVERSE EFFECT IN RESPONSE TO A DRUG TREATMENT
http://www.wipo.int/pctdb/en/fetch.jsp?LANG=ENG&DBSELECT=PCT&SERVER_TYPE=19&SORT=1171397...
And BTW, while the incidence of myopathy has been reported as high as 5%, the number of patients that suffer at least mild ADR's may be significantly higher:
An "adverse statin response" is any negative response to statins, particularly a muscle adverse response such as a myopathy, rhabdomyolysis, and the like. Methods for identifying a muscle adverse effect are well known and include, for example, measuring creatine kinase, wherein increased levels above normal are indicative of adverse response to statins. About 20% of patients who take statins complain of muscle ache, and elevated creatine kinase levels are indicative of myalgia (muscle injury).
If I were you guys, I'd give all that math a rest until I really knew what I was talking about. I recognize that in your case Frog, that's never stopped you before and is not likely to now. But you ought to think about exercising a little better restraint in the future. Afterall, you only have two feet and I think you already swallowed one.
BTW, is it true? Do Frog legs really taste like chicken? LOL
Later,
W2P
This is just too easy. I choose F.
F. Quote directly from one of the Lead Researchers
This brings me to my next question. With the 500K Array Set and this next-generation array, we now have tools to assess SNP genotypes, copy number variant profiles and expression patterns. These could be thought to represent three non-overlapping dimensions of genetic information. How do you envision such information being combined in genetic studies moving forward?
Scherer: Ultimately, it would be ideal if we had a single platform that allowed us to detect all of these different genomic profiles from DNA to RNA all at the same time in one experiment. I don’t think that exists.
The next-best scenario is to have at least two of them. We already do, of course. You can assess SNP genotypes and then CNVs on the Affymetrix 500K Array, as we did for the consortium study. Overlaying the gene expression data will also be crucial because we now know that both SNPs and CNVs can either directly or indirectly affect gene expression.
Gee, it doesn't sound as if this researcher is telling us that SNPs are a thing of the past. In fact what he says is that they "know" that SNPs can either directly or indirectly affect gene expression, and that the best scenario is to have a genotyping system that can look at both SNPs AND CNVs.
Secondly, it is clear from your posts over on RB that your understanding of CNVs is that they solely represent instances of multiple copies of genes or sequences. If you'd do a little reading prior to making these outlandish statements you'd understand that a CNV isn't necessarily a multiple copy type of variant.
In fact, CNVs are not a "new" discovery. Geneticists have known about and studied them for years. The significance of the latest work is the size and volume that were discovered. But, there are many types of variations that are classified as CNVs. That 12% variation they refer to includes insertions and, in some cases, deletions of entire sections of chromosomes that had NO apparent affect on the individual. How much of the newly discovered variation has any significance at all is not known at this time. The conclusions contained in your posts have clearly NOT been drawn by the researchers that conducted the work.
They also know that there are more to find, but there are technical issues that need to be overcome. Most notably to THIS discussion would be the fact that in order to detect and study those in the more complex regions of the genome, they'll FIRST need to find MORE SNPs:
Because they were complex, they were often dropped out of the HapMap Project. So there may be a paucity of SNPs there. As a result of that, they are not well represented on SNP arrays, as one would expect.
So there is some ascertainment bias away from us being able to detect these regions and make correlation studies. If nothing else, we know now that these regions are complex. Even if we can annotate those that are simpler versus those that are complex, we still have to make a special effort to have a representation on arrays that are developed going forward.
For the bi-allelic-type CNV regions, we may be able to tag them using either existing or new SNPs in a typical manner. Based on the data in the Nature paper, we may be able to follow a CNV using a tagged approach about 25 to 30 percent of the time. But certainly for at least 50 percent of them, either new representative SNPs will have to be developed. Alternatively, you might develop a tailored array that would cover SNPs and CNVs using either classical SNP coverage or non-SNP oligonucleotides targeted to specific regions of the genome. That would be very, very valuable.
Are we getting the picture here Frog? The SNPs provide the signposts on the roadmap around the genome. The SNPs enable researchers to delineate a region so that they CAN study it.
BTW, Frog, I thought you told TonyTox on the other board that you couldn't do this work using existing equipment. In fact I'm certain you did. Here's the text:
http://ragingbull.quote.com/mboard/boards.cgi?board=DNAG&read=362547
...and what about the equipment manufacturers? do researcheres still use genotyping machines for this work or do they use something else?
They certainly can't use them in their existing state. They will either need new machines or more complex software.
So how did they manage to do this on an Affymetrix 500K Mapping Array? In fact, Affymetrix was touting this accomplishment quite proudly. You said it couldn't be done. I guess they didn't check with you first, huh?
I could go into some of the other erroneous statements contained in that TonyTox response, but we'd be here all day.
The bottom line is that you've never really understood DNAPrint's classifiers (hell, I don't think you even understand that it's not necessarily the SNP's themselves that cause the variable response.) The SNPs are markers, signposts that point to relevant sections of DNA. Many times NOT linked genetically to the trait that the classifer infers. IMO, far from making the classifiers obsolete, this new information could prove quite valuable to the company in helping them better understand the biology behind the inferences provided by the classifiers.
How does a seemingly unrelated region of DNA impact a trait without being genetically linked to the trait? Maybe CNVs will help explain. Equally possible, maybe they can't.
Later,
W2P
I'll tell you what. I have evening plans. You go ahead and put that foot a little further into your mouth. I'll help you get it the rest of the way in tommorrow.
Later,
W2P
bag8ger...Why on earth do you assume that Frog knows anything about SNPs or CNVs. SNPs are essential elements to any research, and will continue to be. You CAN'T identify CNVs without SNPs. The latest research is additive to our knowledge base, it doesn't replace or erase the significance of SNPs. Geez...
Later,
W2P
I know you've made a very similar statement over on another board. Suffice it to say, it demonstrates quite clearly your complete misunderstanding of genetics and the meaning of the new research.
Wow, you actually know far less than I even gave you credit for, and that wasn't much to begin with. Don't have the time right now but I'll provide a complete response later.
Later,
W2P
Thought this of interest in relation to the PR this week. From Cannon Pacific website (scroll down to "City Talk", City of San Diego):
http://www.cannonpacific.com/Municipal_Cities.asp
City Talk
--------------------------------------------------------------------------------
"Our use of innovative Informative Technolgy (GPS and GIS) in our sweepers continues to set the model for other agencies to follow."
--------------------------------------------------------------------------------
City of San Diego
Later,
W2P
Who was it that said DNAP doesn't do Whole Genome Analyses?
Ramona Coopersotck, Ph.D. | Manager, Genotyping Services
Dr. Cooperstock completed her B.Sc. in Biochemistry at the University of Victoria. She completed her Ph.D. at the University of Toronto on RNA regulation during Drosophila embryonic development. She was a Research Associate at the University of Toronto where she developed a functional genomics project for the model organism C. elegans. Dr. Cooperstock has an extensive background in Molecular Biology and Genomics as well as in project development and management. Dr. Cooperstock joined Ellipsis in January 2006. Her broad experience and skills in molecular biology are a critical asset to advising, designing and interpreting our clients' genotyping and related service needs. She was recently responsible for the successful launch of our new services in whole genome genotyping analyses and expression.
http://www.ellipsisbio.com/services/index.html
http://www.ellipsisbio.com/Ellipsis%20Fact%20Sheet.pdf
It would appear there have been a few updates to the Ellipsis Biotherapeutics website, as well as a few personnel additions.
BTW, and this the first I've seen it confirmed, but if you peruse the site you will find that the intellectual property portfolio in Crohn's disease was part of what DNAPrint acquired in the Ellipsis deal. It's actually stated in Rubin's bio for anyone interested.
This is just FYI. As always, do your own Due Diligence and make your own investment decisions.
Later,
W2P
frog...last things first...
DNAPrint's 18% stake preceded the Bond. You'll recall that DNAPrint's initial purchase also included an obligation to take a much larger stake in Biofrontera (49% comes to mind), should Biofrontera have failed to secure at least a 10,000,000 Bond prior to January 2006. Biofrontera, in fact, secured 20,000,000 by the end of August 2005, which alleviated DNAPrint's obligation to take a further interest.
Concerning any dilution pending conversion, it is true that conversion will ultimately add approximately 25% to the float, but remember that the float is quite small at this stage, and the conversion rate is fixed.
I think it's reasonable to assume that the other Biofrontera insiders shares carry the same one year restriction as DNAPrint's shares. As we've already established, that means fully 2.5M of the 4.4M are restricted. At this time, the only freely trading shares are the 655K IPO shares, about 15% of the total. Presumably, Biofrontera should be well along (perhaps completed) with their first Stage III Clinical trial before the restrictions are lifted this time next year. Assuming they are successful, the share price should benefit from the extremely low float.
As far as the convertible shares are concerned, the Bonds are convertible at a fixed price of $16.13 euro share. In other words, it doesn't even make sense to convert until the price advances beyond $16.13 euro, and shorting the stock will not get the bondholders more shares, it would only reduce the likelihood that they could convert. The only way the bondholders benefit by converting is if the share price has exceeded the conversion price (which would also be good for us).
As importantly, the bonds themselves are a relatively low risk investment. The principle is secure, it is producing an 8% coupon return, and the holders stand to receive a return of capital at maturity. Thus, there is no great urgency for the holders to convert, and certainly no incentive to convert in a way that would drive the market price of the stock below $16.13 euro.
Should the share price appreciate it will be up to each bond holder to determine when it makes sense to convert based on the additional risk he will be assuming by trading a fixed income position for an equity position. But even if the market value of the shares appreciates to a point that makes it desirable to convert 100% of the bonds, this company will have a tradable float of only about 1.9M shares.
I haven't been a great fan of management these last two years, but I have to give them their due on this one. And whoever put together the strategy did a nice job IMO. By structuring the financing this way, the interests of the bondholders are directly aligned with the interests of the shareholders, which is the way it should ALWAYS be.
Now the question is, will we see something like this replicated in the case of DNAPrint Pharmaceuticals? If not, it won't be because they don't know how it should be done...
All of this is JMHO and should be taken as such. As always, do your own DD and make your own investment decisions.
Later,
W2P
frog...Here's the math.
Biofrontera's latest PR concerning the IPO states that a total of 665,271 shares were issued in connection with the combined private placement and associated options. They also state that the outstanding share capital after the IPO is 3,205,403. Subtract the 665,271 from 3,205,403 and you arrive at 2,540,132 shares prior to the offering.
DNAPrint PR's prior to the IPO stated their ownership position at 455,234 shares. Divide 455,234 by 2,540,132 and you get DNAPrint at a pre-IPO ownership percentage of 17.9% (approximately 18%).
Everything else being equal, the IPO shares themselves would only have reduced DNAPrint's 455,000 shares to a 14.2% ownership position, but after the stock started trading, the convertible bondholders came into consideration. This is from Biofrontera's PR concerning the issuance of the $20,000,000 convertible bond:
The partial debentures can be converted to shares at a conversion price of € 16.13 per share, contingent upon the anti-dilution clause defined in the conditions of the convertible bond. After the conversion of all partial debentures the participation of the bond creditors in Biofrontera will correspond to one third of the company, relating to a pre-money company valuation of € 40 mln. The convertible bond is intended to prepare for the IPO of the company.
The option to convert the debentures at a fixed rate can be exercised at the earliest three months after the shares of the company are traded at a stock market, or at a change of control of the company.
The shares associated with the bonds were always contingent upon the IPO. Without an IPO the shares would never exist, only a loan that would have to be repaid. But after the IPO the dilutive effects of the bonds must be considered in order to accurately depict DNAPrint's ownership position. The bonds are convertible into a total of 1,239,926 shares of common stock, which when added to the 3,205,403 will bring the total outstanding shares after conversion to 4,445,329.
Based on 4,445,329 fully diluted shares, DNAPrint's ownership position of 455,234 equates to 10.24%.
This is, of course, based only upon my reading of the available public documents and represents MHO. This may or may not be a correct interpretation. Please do your own DD and make your own investment decisions.
Later,
W2P
Dr. Depresso...perhaps if you checked your facts you'd have a more positive opinion of your investment...
In your opinion as a lawyer, or accountant, or whatever you are...do you believe that a Swiss Bank would float $500,000 on a one year loan to a company that as you put it..."will most likely close its doors well within 12 months, at the outside"...I think you need to think that one through again. And don't tell me it's because it is so cold in Switzerland that the bankers can't maintain a "room temperature IQ".
You say that DNAPrint's managers are..."lavishly compensated managers and staff who are not required to paid based on merit or performance"...Are these the same managers that seem to have parlayed an approximate $2,000,000 investment in Biofrontera into an approximate $10,000,000 corporate asset in less than three years time? You might want to reconsider that opinion as well.
Lastly, you say..."The situation with DNAG has rapidly progressed from bad to worse to tragic to absolutely deplorable within the last year."...To the contrary, DNAG is holding a $10,000,000 asset against which they can borrow rather than rely strictly on dilution to fund their business plan; they have aquired a pipeline of patent protected drug candidates that seem to be progressing nicely; they have established research collaborations with some of the most prestigious institutions of higher learning in the U.S.; and the way I read it, there is less than a year now until expiration of the "option". You are HALF right, though..."The situation with DNAG has rapidly progressed"...
Of course this is JMHO...from the facts. Do your own DD and make your own investment decisions. I'll see you in about a year, unless something TRULY depressing happens and you need me to help you through it. LOL
Later,
W2P
frog...Pardon me for jumping in here, but it is my understanding that Phase I Clinical Trials involve relatively few patients (I have seen numbers ranging from 20-100).
Cost estimates I have seen range from $5,000 to $10,000 per patient.
Given these assumptions, wouldn't you agree it may well be within DNAG's ability to complete the Phase I, and perhaps the Phase II work using their existing funding mechanisms?
And if the $600,000 they just committed covers the cost of the required pre-clinical work, I don't see a tremendous financial burden until they would reach the Phase III trial stage.
JMHO
Later,
W2P
I know stockholder already posted the text, but for anyone interested, here are a couple of links:
http://news.morningstar.com/news/DJ/M06/D23/200606230854DOWJONESDJONLINE000547.html?Cat=USMkts
http://translate.google.com/translate?hl=en&sl=de&u=http://www.n-tv.de/681943.html&sa=X&....
This one indicates that Biofrontera would like to use up to 25% of the proceeds to acquire new dermatology drug candidates:
http://64.233.179.104/translate_c?hl=en&sl=de&u=http://www.finanztreff.de/ftreff/news.htm%3F...
Looks like the subscription period will start on June 27th, 28th, or 29th and end in about a week, give or take a few days.
Later,
W2P
PS...Chris...remember "Fantasy Island"? Boss...da plone, da plone...! LOL Good to see 'ole spooky is still hangin around...
880...Been a long time fan of coffee myself...lol
This is JMHO, of course, but I'll be watching with interest. The possibilities are numerous. The bottom line is that we really only know a few of the details concerning the offering so everything we post is speculative. I will offer the following based on what I've read in recent news items and caution you to consider it in the context it deserves.
But here's what we know:
DNAPrint owns approximately 455,000 shares of Biofrontera or an 18.3% stake. From that information we can estimate the total existing privately held shares of Biofrontera at approximately 455,000/.183 = 2,486,338 shares (call it 2,500,000 shares for simplicity sake)
According to the article stockholder101 posted the other day, here's the link (http://investorshub.com/boards/read_msg.asp?message_id=11570904), Biofrontera intends to offer a total of 2,185,000 shares in the IPO. But only 1,900,000 of those shares are new shares. 285,000 existing shares are part of a secondary offering by existing shareholders. Private shareholders in an IPO will often do that to recoup a portion of their earlier investment.
Also, the article tells us that the remaining shares of the existing shareholders (those not participating or only partially participating in the secondary offering) will be subject to a 12 month lockup period. This is done so that existing shareholders can't sell into the IPO and place immediate downward pressure on the share price.
Anyway, it looks as if there will be about 4,400,000 shares outstanding after the IPO.
So what are the possibilities:
If everything were to remain status quo, DNAPrint's overall share of the company would be something like 10.3% (455,000/4,400,000) after the IPO. DNAPrint's equity stake would, therefore, be worth 10% of the total IPO value, but the shares would not be saleable on the open market. Depending on the success of the IPO, the value of their shares could likely range IMO from 5,000,000 to 10,000,000 euros. The current exchange rate is around 1.25 so we could conceivably show $6,250,000 to $12,500,000 in current assets on our next balance sheet.
Of course this assumes status quo and assumes a 50,000,000 to 100,000,000 euro range for the IPO. The value could be up or down from either end of the range.
It is also possible that existing shareholders shares will be restructured as part of the offering. Often, shares are made convertible at some multiple to limit the dilutive effect of the offering on the voting power of their shares. We don't know what the share structure will look like, but it is possible that the current structure would change.
A third possibility, which I would find pleasant would be a scenario where DNAPrint is participating in the secondary offering. Frankly, if I were running the company I would be offering half of my shares in that offering. I would probably still retain a 5% stake in Biofrontera (a significant ownership position), but by selling 225,000 of my shares in the IPO itself I could bring approximately 10% of the IPO to MY company in cash. If the IPO goes for 50,000,000 euros, DNAPrint would generate $6,250,000 in immediate cash, and still retain a balance sheet asset of $3,125,000 for their remaining investment in Biofrontera. This strategy would bring a total of $9,375,000 to the balance sheet assuming an IPO value of 50,000,000 euros. You could double those numbers at the higher end if you like to speculate. On the other hand, DNAPrint may not be offering ANY of their shares in the secondary offering, which would IMO be foolish.
Anyway, according to the article there is expected to be a Biofrontera press conference on June 26th regarding the IPO. They could also be releasing clinical trial data to generate interest in the offering.
Let's hope that DNAPrint managment is able to share additional information with the shareholders at the meeting on Thursday. Otherwise we, unfortunately, have to just sit back and trust that management has a plan. Either way, I see enhanced intrinsic value for my shares.
How will the market react? Who knows...that's what happens in a market.
Later,
W2P
lulu...You're kidding right? OK, answer this. If you're a private citizen with $10,000,000 worth of real estate...paid...what does that have to do with your net worth?
That's as simple as it gets...I hope it's not too difficult a concept for you.
Later,
W2P
lulu are you lala?
http://www.biofrontera.com/cms/index.php?id=25
Looks a little sooner to those of us with brains...lol
Scroll down and take a look at the Supervisory Board. A couple of new names...very interesting:
David Ebsworth, PhD - former Head of Bayer's North American Pharmaceutical Operations. Current Chairman of Curacyte AG, Non-Executive Director at both Curagen and SkyePharma:
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/10-20-1999/0001048737&...
http://80.243.45.221:8080/opencms/opencms/curacyte/directors.htm
http://diplomacy.shu.edu/world_leaders/gala/
http://www.curagen.com/corporate/manage.asp#bod
http://www.skyepharma.com/management.html
Has the look of a real heavyweight, wouldn't you say LULU? Oh, and note that he will be replacing Professor Abshagen, who is retiring from the board "AFTER THE IPO".
I just can't figure out what he would be doing with Biofrontera. Maybe he's just...how did Dr. Wacky put it..."aligning himself with a small wannabe engaged by DNAG management for cosmetic publicity?"
Later,
W2P
Not sure what the the excitement is all about concerning the statin application, but the Preliminary International Examination Report indicates that the claims in the Ovanome Patent are "novel", "inventive", and have "industrial application":
http://www.wipo.int/patentscopedb/en/wads2.jsp?IA=US2002038345&LANGUAGE=EN&ID=id000000004830....
When you reach the page, use the arrow at the top to advance to page 3.
Later,
W2P
BTW, zoolulu, you ARE a sap (senseless...annoying...pathetic) If you want to know what is said at a shareholder's meeting, I suggest you get on your moped and make the trip down. Your next chance is later this month.
Gcbr...nothing to worry about...dr frudaky just has his slopster-slasher up Zooluu's oobe3 and they're all atwitter with anticipation. Hopeful-ly they'll get the matter straightened out soon.
BTW, here's a riddle for you. How many scumbags does it take to avenge a loser?
Answer: We won't know until they're all here...or over on RB as the case may be...LOL
Goodnight boys...sleep tight.
Later,
W2P
kermy...So tell me, just how just how many bases do you think make up the average gene? (Here's a clue for you...apparently not nearly as many as you think...LOL)
After you figure it out, perhaps you'd like to revisit that specification I posted awhile back.
Later,
W2P
kermy...lol Perhaps you'd like to explain to the board how it is possible to, how did you put it, "...existing data from the public domain was reviewed, and the the resulting 'mined' data shows previously unreported snps." Ah, excuse me, but that's just not possible.
Actually, you can't "score" a genotype until the SNP's have been discovered. And since they didn't exist in the public databases, only resequencing would produce the data needed to identify the SNP. It's a chicken and egg thing...I wouldn't expect a frog to know.
You see tadpole, the problem back in 2000 and 2001 was that the human genome sequence that DID exist came from only a few individuals, and the vast majority of it came from only a single individual. There was only about 10% overlap that came from multiple individuals due to overlapping clones of different chromosomes that were sequenced. And since a SNP must have a frequency of at least 1% in coding regions, and 10% in non-coding regions to even QUALIFY as a SNP...well, I'm sure you can see the problem for the SNPsters.
Since these SNP's didn't exist in the public database, and since there is a frequency threshold required to even qualify as a SNP, the only way to "score" those 500 individuals was to first have "completely sequenced" the relevant genes and identified the SNP's. Ergo, ipso, facto, you're on the wrong side of this argument...AGAIN.
Later,
W2P
P.S. You REALLY need to get a better understanding of the terms "sequencing" and "re-sequencing" before our next exchange. This is getting embarrassing.
kermy...I take it this is the invite to provide the information. So be it.
The following is taken from DNAPrint's 55 page response to the patent Examiner reviewing the Statin Classifier patent. These arguments are being made by Ms. Lisa Haile, PhD, JD on behalf of DNAPrint:
http://portal.uspto.gov/external/portal/!ut/p/_s.7_0_A/7_0_CH/.cmd/ad/.ar/sa.getBib/.c/6_0_69/.ce/7_...
Those genes, including HMGCR and CYP3A4, were selected for the investigations that lead to the invention, and were analyzed for the presence of all SNP's, whether related to Statin response or not. Specification at 110, [0278]. Specifically, the identified genes from DNA samples of a population of 500 unrelated, multi-ethnic donors were scored, resulting in the identification of 25 SNP's in the HMGCR gene and 23 SNP's in the CYP3A4 gene. Id. At 133, [0328]. The specification teaches that none of the SNP's identified thereby were previously known in the literature or reported in the NCBI dbSNP Database. Id.
This from page49:
The present Specification teaches that "[t]he public genome database was constructed from a relatively small collection of donors", and thus, the relevant SNP's may be under-represented or biased against in the public human SNP and Unigene Databases." Specification at p. 110, [0278]. Considering these facts, Applicant completely resequenced the CYP3A4 and HMGCR genes in a large, multi-ethnic population (n=500). Id. at 133, [0328]. Notably, none of the SNP's of the present invention had previously been reported. Id.
It continues later on the page:
Finally, Applicants submit that post-filing art not sited by the Examiner supports and confirms the correlation to a number of the claimed SNP's. See, for Example, variations catalogued in GeneBank Accession No.: AY321356 (Exhibit F).
I rest my case...
Later,
W2P
bag8ger...You're a good guy, but you're really not helping here. You give frog much too much respect. He really is lacking in understanding...he just puts on a good show.
DNAPrint DOES sequence genes, and they HAVE discovered SNP's that were previously unreported in the public databases...period. If the long-of-tongue one responds to my last post, I'll be happy to post irrefutable evidence to support my arguments.
Later,
W2P
genius...mayhaps you'd best look up the definition of "resequence". You seem to be confused. It has NOTHING to do with reviewing the public database.
And, as a matter of fact, I can provide documentation for my argument. Although it WILL make you look awfully foolish. Are you SURE you want to go there...lol
Later,
W2P
toad...I thought we settled this...they DO sequence and they HAVE discovered SNP's. Do you ever actually READ the patent applications or arguments?
Later,
W2P
kermy...Sorry, but it means exactly what it says it means. DNAPrint has, from the beginning, owned an ABI3700 sequencer. You know, the same machine Celera used to sequence the genome? (OK, Celera used a BUNCH of 'em)
Here you go buckshot, but I suggest you do a little more homework. Mykel may have made a couple of minor mistatements, but it's clear he has a good working knowledge. You my friend should stick to engineering:
http://investorshub.com/boards/read_msg.asp?message_id=10766897
PCR amplification (Editor's Note: You ARE familiar with the PCR process, correct?) was accomplished using pfu Turbo polymerase according to the manufacturer's guidelines (Stratagene, La Jolla, CA). We developed a program (T. FRUDAKIS, M. THOMAS, Z. GASKIN, K. VENKATESWARLU, K. SURESH CHANDRA, S. GINJUPALLI, S. GUNTURI, S. NATRAJAN, V. K. PONNUSWAMY and K. N. PONNUSWAMY, unpublished results) to design resequencing primers (Editor's Note: Are you familiar with primers, i.e. oligonucleotides, and their use?) in a manner respectful of homologous sequences in the genome, to ensure that we did not coamplify pseudogenes or amplify from within repeats. BLAST searches confirmed the specificity of all primers used. Amplification products were subcloned into the pTOPO (Invitrogen, San Diego) sequencing vector and 96 insert-positive colonies were grown for plasmid DNA isolation (the use of 670 individuals for the amplification step reduced the likelihood of an individual contributing more than once to this subset of 96 selected). We sequenced with an ABI3700 using PE Applied Biosystems BDT chemistry and we deposited the sequences into a commercial relational database system (iFINCH, Geospiza, Seattle). PHRED-qualified sequences were imported into the CLUSTAL X alignment program and the output of this was used with a second program that we developed (T. FRUDAKIS, M. THOMAS, Z. GASKIN, K. VENKATESWARLU, K. SURESH CHANDRA, S. GINJUPALLI, S. GUNTURI, S. NATRAJAN, V. K. PONNUSWAMY and K. N. PONNUSWAMY, unpublished results) to identify quality-validated discrepancies between sequences. We selected those for which at least two instances of PHRED identified variants that scored 24, and each of these SNPs discovered through resequencing were used for genotyping.
http://www2.carthage.edu/~pfaffle/hgp/ABI3700.html
Would you STILL like to claim that they've never sequenced anything? Boy, you are the same 'ole frog though...thick, yet obstinant.
Time to go now...have fun with your friends.
Later,
W2P
Mykel...I see you're having some fun with my old buddie, the toad. I stopped arguing with him long ago. I am a biologist by education, he's an engineer...lol But like most engineer's I know, you can't tell them ANYTHING because they know EVERYTHING! lol
Hey Frog, if they don't sequence then what's this doing on their website:
http://www.dnaprint.com/welcome/productsandservices/otherproducts/genotyping/
Genotyping
DNAPrint also provides certain services to industrial partners. DNAPrint™’s services range from sequencing and genotyping to the entire process of SNP discovery. Tell us what your goals are and we can tailor our services to meet your needs.
Have fun Mykel...he CAN be entertaining.
Later,
W2P
P.S. Kermit, I know you miss me but I just don't have the time to play that I used to...
I'm confused about something. This from the Dutchess Agreement, Section 3(C) on page 8 of the agreement:
http://www.sec.gov/Archives/edgar/data/1127354/000114420404015688/v07224_ex10-49.txt
(C) SECTION 9 OF THE 1934 ACT. During the term of this Agreement, the Investor will comply with the provisions of Section 9 of the 1934 Act, and the rules promulgated thereunder, with respect to transactions involving the Common Stock. The Investor agrees not to short, either directly or indirectly through its affiliates, principals or advisors, the Company's common stock during the term of this Agreement.
This from the most recent 10K:
http://www.sec.gov/Archives/edgar/data/1127354/000123174206000203/dnag10ksb.htm
DUTCHESS MAY SHORT SELL OUR STOCK DURING THE PERIODS WE ISSUE A PUT WHICH MAY CAUSE OUR STOCK PRICE TO DECREASE.
Pursuant to the Investment Agreement, Dutchess has the right to short sell the amount of stock we expect to issue to them during the period we issue a put. If Dutchess actually sells our stock short, our stock price may decrease. If our stock price decreases, you may lose some or all of your investment.
So which is it? And if the second scenario is true, when was the change made and why weren't the shareholders made aware of it?
Later,
W2P
Dorsey...The link didn't work on RB either. Go to Investorvillage. It works fine there.
Later,
W2P