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Naked and Confused
Jessica Simpson ? Paris Hilton ?
No , but just as unsettling :
Money & Investing
Naked and Confused
Liz Moyer 02.12.07
How a tiny software outfit fell victim to an illegal but unrestrained practice known as naked short-selling.
Most investors have never heard of Sedona Corp., a piddling Pennsylvania outfit that sells customer relationship management software for small U.S. banks and credit unions. But to a rogue band of short-selling hedge fund managers, Sedona was prime meat.
Full story at Forbes :
http://www.forbes.com/home/free_forbes/2007/0212/068.html
>> To get way OT, you can use microwaves and chocolate chips or marshmellows to calculate the speed of light. <<
Also way OT. You can use your microwave to create your own little Fourth of July display , using just a Brillo Pad.
Sorry , no link. Just speaking from my own recent disinfecting experience.
Too often , these debates are not based on a rational evaluation of the science but are instead a reflection of whose ox is being gored financially. The same thing happened with H. pylori in ulcers / gastric cancer and it's unseemly , to say the least.
The tobacco industry could take lessons from the medical industry , IMO.
Chopping off protein puts immune cells into high gear
(The ability to regulate this system at the regT or effector T cell level , maybe by targeting an appropriate protease / protease inhibitor to CD127(hi)-cells , could provide a means to 'tune' an immune response in autoimmune disease , therapeutic vaccines , etc.)
Memphis, Tennessee, January 24, 2007
The complex task of launching a well-organized, effective immune system attack on specific targets is thrown into high gear when either of two specific enzymes chop a protein called LAG-3 off the immune cells leading that battle, according to investigators at St. Jude Children's Research Hospital.
These cells, called T lymphocytes, are key to the body’s ability to fight off infections, tailoring the immune response so it focuses on specific targets. When activated, certain T lymphocytes called effector T cells reproduce, increasing their numbers and enhancing their ability to protect the body.
The St. Jude finding is important because it represents a new concept in how T cells are regulated, according to Dario Vignali, Ph.D., associate member of the St. Jude Department of Immunology. The study offers the first example of a protein that is required for dampening T cell activity being controlled by getting chopped off at the T cell’s surface. Certain drugs that inhibit metalloproteases now under development as treatments for multiple sclerosis and arthritis appear to work by keeping T cells on a tight leash, Vignali noted. The new discovery could demonstrate an additional way in which these drugs work. Vignali is senior author of a report on this work that appears in the January 24 issue of The EMBO Journal.
The investigators performed their studies using animal cells that were genetically modified to carry LAG-3 on their surface; the researchers also used drugs that inhibit enzymes that chop off LAG-3. The team demonstrated that the two enzymes that cleave LAG-3 are controlled by of distinct but overlapping signals generated from the T cell receptor, a specialized protein that allows T lymphocytes to “see” the outside world. The investigators showed that the T cell receptor generates a different, specific signal to control the activity of these metalloprotease enzymes, called ADAM10 and ADAM17.
Specifically, the team demonstrated that ADAM10 normally cleaves LAG-3 even before the T cells are activated. After the T cell receptor receives signals from the immune system, it causes the gene for ADAM10 to make much more of this enzyme, substantially increasing the rate of LAG-3 cleavage. However, ADAM17 is inactive until the T cell receptor triggers a molecule called protein kinase C theta to activate this enzyme. In either case, when metalloproteases remove LAG-3, the brakes are taken off T cell activity.
“Appropriate control of T cell expansion during an immune response is critical,” Vignali said. “We have uncovered a new paradigm in which specialized cell surface enzymes control this process by modulating the expression of a molecule, LAG-3, that acts as an immunological molecular brake. In turn, this process is controlled by the strength of the T cell receptor signal—the immunological ‘accelerator.’ So the more the T cell ‘accelerates,’ the more the ‘brake’ is released.”
The St. Jude team previously reported that regulatory T cells, which prevent effector T cells from running out of control and causing damage to the body, use LAG-3 to rein in these activated effector T cells (http://www.stjude.org/media/0,2561,453_5297_16097,00.html). The current study in EMBO extends that finding by showing that cleavage of LAG-3 proteins on the surface of T cells allows them to greatly increase their proliferation rate during such a battle. The team also showed that cleaved pieces of LAG-3 do not contribute to T cell control, but are rather “waste” products that are swept away later.
The other authors of the paper include Nianyu Li (formerly at St. Jude; now at Amgen Inc., Thousand Oaks, Calif.), Yao Wang, Karen Forbes, Kate Vignali and Creg J. Workman (St. Jude); Bret S. Heale and John J. Rossi (Beckman Research Institute of the City of Hope, Duarte, Calif.); Paul Saftig (Christian-Albrechts University, Kiel, Germany); Dieter Hartmann (Leuven and Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium); Roy Black (Amgen Inc.; Seattle); Carl P. Blobel (Weill Medical College of Cornell University, New York); and Peter J. Dempsey (University of Washington, Seattle).
This work was supported in part by the National Institutes of Health, a Cancer Center Support CORE grant, ALSAC and the German Research Foundation.
http://www.stjude.org/search/0,2616,582_3161_22470,00.html
American Stock Exchange to Host First Annual Healthcare Conference in Boston on February 8, 2007
Monday January 22, 9:00 am ET
Leading Healthcare Companies Scheduled to Present
NEW YORK, Jan. 22 /PRNewswire/ -- The American Stock Exchange® (Amex®) today announced that it will host its First Annual Healthcare Investor Conference in Boston on Thursday, February 8, 2007. Companies scheduled to present include leading Amex-listed healthcare companies. The conference will be held at The Fairmont Copley Plaza, located at 138 St. James Avenue.
"The American Stock Exchange is committed to enhancing the visibility of its listed companies. Our industry-focused conferences are just another example of this commitment and provide our issuers a platform to address a highly targeted group of investors. We are pleased to add healthcare to our annual conference calendar and believe this will deliver significant value to our listed companies operating in this space," said John McGonegal, Amex Senior Vice President of Equities.
Presenting companies include:
SCOLR Pharma, Inc. (AMEX: DDD - News)
ADVENTRX Pharmaceuticals, Inc. (AMEX: ANX - News)
Caraco Pharmaceutical Laboratories Ltd. (AMEX: CPD - News)
RegeneRx Biopharmaceuticals, Inc. (AMEX: RGN - News)
Dyadic International, Inc. (AMEX: DIL - News)
Inverness Medical Innovations, Inc. (AMEX: IMA - News)
Psychemedics Corporation (AMEX: PMD - News)
Isolagen, Inc. (AMEX: ILE - News)
Five Star Quality Care, Inc. (AMEX: FVE - News)
Idera Pharmaceuticals, Inc. (AMEX: IDP - News)
MINRAD International, Inc. (AMEX: BUF - News)
I-trax, Inc. (AMEX: DMX - News)
Javelin Pharmaceuticals, Inc. (AMEX: JAV - News)
Immtech Pharmaceuticals, Inc. (AMEX: IMM - News)
MTS Medication Technologies, Inc. (AMEX: MPP - News)
http://biz.yahoo.com/prnews/070122/nym138.html?.v=66
( I think you can get webcast links at the individual company websites. The AMEX link , http://tinyurl.com/3cbnp6 , doesn't show a schedule yet. )
Here are some results from DDW '06 :
http://www.natap.org/2006/DDW/DDW_19.htm
We're all anxiously awaiting the announcement of the game plan for nonresponders. The pending ribavirin interaction study probably has something to do with the delay.
Interview with Josh Boger of VRTX
http://www.itconversations.com/shows/detail1710.html
EDIT : Still listening. It's basically 'Antiviral Drug Discovery for (real) Dummies'
Osiris (OSIR) is another company to keep an eye on in the GVHD area. They're in P3 with Prochymal ( adult stem cells ) for steroid-refractory GVHD and have Orphan status in the US and EU.
OSIR was one of the best performing IPOs last year.
New ASCO disclosure rules for docs
Seattle Times article :
http://tinyurl.com/232ta2
Report from ASCO GI
Pancreatic cancer vaccine may help some patients
( Not sure if the Hopkins data are new but the Avastin results are not . )
Sat Jan 20, 2007 6:37pm ET
WASHINGTON, Jan 20 (Reuters) - A tailor-made cancer vaccine may help patients with pancreatic cancer, who have few other options to treat the deadly disease, researchers reported on Saturday.
Most of the patients who got the vaccine survived at least two years, Dr. Daniel Laheru of Johns Hopkins University in Baltimore and colleagues told a meeting of gastrointestinal cancer specialists.
In the phase II study of 60 patients, 88 percent were alive a year later and 76 percent lived two years.
In comparison, 63 percent of patients treated with surgery alone survive a year and 42 percent live two years.
"Our initial review suggests that the vaccine could provide additional benefit over chemoradiotherapy, but prospective randomized trials are needed to confirm this observation," Laheru said in a statement.
Chemoradiation therapy involves chemotherapy and radiation together, and is done after surgery.
Pancreatic cancer is one of the deadliest cancers. In the United States alone, it will be newly diagnosed in 37,170 patients and will kill 33,370, according to the American Cancer Society.
Laheru's team concocted a therapeutic vaccine -- one that fights a disease by boosting the immune system rather than preventing the disease.
He presented his findings to the 2007 Gastrointestinal Cancers Symposium in Orlando, Florida, co-sponsored by the American Gastroenterological Association, the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.
The team took cells from the patients' tumors, killed them using radiation, and then genetically engineered them so they would produce a compound called GM-CSF. GM-CSF attracts immune cells to the vaccine site, where they find and learn to recognize pancreas cancer proteins.
Then the immune cells patrol the rest of the patient's body and, in theory, destroy pancreas tumor cells.
A second team reported bad news -- adding Avastin, a drug that starves tumors of their blood supply, to the standard chemotherapy for pancreatic cancer did not help patients live any longer.
Dr. Hedy Kindler of the University of Chicago and colleagues tested Avastin, known generically as bevacizumab. It was developed by San Francisco-based Genentech (DNA.N: Quote, Profile , Research) and is sold by Roche (ROG.VX: Quote, Profile , Research).
Their phase III trial of 600 advanced pancreatic cancer patients added Avastin to the standard treatment, Eli Lilly and Co's (LLY.N: Quote, Profile , Research) Gemzar.
But those given Avastin did not live any longer than those given Gemzar alone -- both groups lived about six months, Kindler's team told the meeting.
"These results were quite disappointing," Kindler said in a statement. "This trial definitively shows that bevacizumab does not improve survival in patients with advanced pancreatic cancer."
http://tinyurl.com/2hvavl
>>> However, DOR said it cannot consider the offer at this time as the company had signed a letter of intent which grants Sigma-Tau Pharmaceuticals Inc., a unit of Italy-based Sigma-Tau Group, exclusive right to negotiate for its lead product. <<<
It sounds like this means rhey can only sell the rights to Sigma-Tau. Is this correct , or does it mean right of first refusal ?
Whatever , it seems this will set a considerably higher floor on DORB pps for a while , at least. Wish I had some myself.
Yahoo : If at first you don't succeed ...
Try , try again !
http://tinyurl.com/ynny4s
January 19, 2007 09:00 AM Eastern Time
Yahoo! Launches Personal Finance Website
New Site Expands Yahoo! Finance From Wall Street to Main Street -- Giving Consumers the Tools They Need to Manage Their Personal Finances
SANTA MONICA, Calif.--(BUSINESS WIRE)--Yahoo! (NASDAQ:YHOO) today launched a new personal finance website, which brings together the Internet’s most useful tools and information to help consumers manage their personal finances. Yahoo! Personal Finance (http://finance.yahoo.com/personal-finance) offers consumers a suite of new financial centers, covering every major area of personal finance, ranging from “Banking & Budgeting” to “Retirement.” The site continues the company’s media strategy of bringing together the best tools and information around a particular topic from the industry’s leading providers, while also expanding advertising inventory in one of the largest advertising categories.
“The goal of Yahoo! Finance has always been to help our users make informed financial decisions, and now we’re able to do that across every aspect of their financial lives,” said Peggy White, general manager, Yahoo! Finance. “Not all of our users manage an investment portfolio, but we all manage a checkbook. This presents a huge opportunity for Yahoo! Finance to expand beyond our core investing-focused offerings.”
Yahoo! Finance has already established itself as the Internet’s number one destination for investing tools and information, and aims to expand its audience size and engagement with the addition of a new personal finance home.
The new Yahoo! Personal Finance features include:
Nine resource centers covering every major area of personal finance, ranging from “Banking and Budgeting” where users will receive helpful information on their daily finances, to a “Taxes” resource center that provides the tools and information consumers need for tax planning. Additional resource centers include: Career & Work, College & Education, Family & Home, Insurance, Loans, Real Estate, and Retirement.
Twenty-five premier content providers, including CNNMoney.com, Consumer Reports, Kiplinger, The Motley Fool, Smart Money, and The Wall Street Journal.
Forty-eight original “How To” guides on a wide range of important financial topics, such as “Plan for the Cost of College” and “Budgeting for a Baby.”
Sixty-six new financial calculators within different financial areas to help consumers estimate everything from “What would my loan payments be?” to “How much will I need to save for retirement?”.
Integration of Yahoo! Answers, featuring editorially-selected user generated questions and answers about a variety of financial topics.
Advice columns from Yahoo! Finance’s 13 financial experts who provide advice exclusive to Yahoo!, including a new career advice column, “The Brazen Careerist,” written by author Penelope Trunk.
A new personal finance glossary from Lightbulb Press, a leading financial literacy publisher.
New Advertising Opportunities
Yahoo! Personal Finance extends Yahoo!’s platform for advertisers who want to reach consumers as they are considering or researching important life decisions. Yahoo! Finance is already a leading destination for marketers across different advertising categories, and expanding into personal finance will help create new opportunities and increase the engagement of the site’s current audience.
The site’s charter advertisers for the launch of Yahoo! Personal Finance include E*TRADE FINANCIAL, LendingTree.com, Intuit TurboTax, Progressive Direct, and Quicken Loans.
About Yahoo! Finance
Yahoo! Finance helps consumers manage their financial lives by providing a comprehensive set of financial services, tools, and information. For investors, Yahoo! Finance offers breaking U.S. and international market news; market data for stocks, bonds, funds, and options; streaming real-time quotes and charts; brokerage research reports, investment analysis and management tools; and community resources that include the most trafficked financial message boards on the Internet. Beyond investing, Yahoo! Finance offers consumers the information they need to make informed decisions across every aspect of their financial lives, covering the key areas.
About Yahoo!
Yahoo! Inc. is a leading global Internet brand and one of the most trafficked Internet destinations worldwide. Yahoo!’s mission is to connect people to their passions, their communities, and the world’s knowledge. Yahoo! is headquartered in Sunnyvale, California.
Fair enough , and on that I'd agree.However ,I think the individual investor has little chance against an increasingly rigged market and , once that becomes apparent to enough people , the appropriate measure to reduce risk may be to put their money under the mattress. It's happened before.
My apologies for the Kudlow comment , though you might not mind if you're a fan of his. It was made before I even brushed my teeth , much less had my coffee fix.
Speaking of Kudlow , he may be claiming that Bernanke has "re-lost his monetary manhood" after today's testimony. Bernanke said that deficits DO matter , and also that tax rates on the rich are on the side of the Laffer Curve such that further cuts , and probably past cuts , would result in reduced receipts to the gov't , not more as Larry loves to proclaim. I'll be interested to hear what he says today. Rather , read what he says , since I'll watch on mute. I get less nauseous that way.
>>> Regulators are outmatched and underfunded. When you put that together with the knowledge that any real reform has to be done on a simultaneous global basis so as to not put the US financial markets at a regulatory (competitive) disadvantage, the best defense is to learn the signs of manipulation and avoid them when you can. <<<
That's the same argument made for not doing anything about global warming and it's a recipe for disaster in both instances.
You sound like Larry Kudlow.
Here's one for HBV pipelines :
http://www.hivandhepatitis.com/hep_b/treatment_chart2.html
Medscape coverage of Liver Meeting
A little dated but it has some comments by docs about Tyzeka and other drugs that might be new to some :
http://www.medscape.com/viewprogram/6151
I found this comment -in bold- by Pockros on the Roche polymerase inhibitor interesting :
""The decreases in HCV RNA from baseline observed with R1626 are greater than those previously described for HCV polymerase inhibitors, and similar to those seen with protease inhibitors," the study investigators report in their meeting abstract.
The investigators intend to begin treatment with R1626 and peg-interferon alfa-2a, with or without ribavirin.
"One question we're trying to answer in our phase 2 study is, do you need ribavirin in the combination therapy or do you not?" Dr. Pockros said. "Up until now ribavirin has been a key ingredient. If our theory holds, then ribavirin would only be required to prevent relapse once therapy is stopped."
They also hope to shorten the current 48-week course of treatment by rapidly reducing viral load at the beginning of treatment, he added."
It sounds like he's thinking about using riba alone after the initial therapy , presumably to function as an immunomodulator. This idea is similar to those being discussed currently for HBV , where the theory is that immunomodulators should be used AFTER the direct antiviral(s) has reduced viral load to near zero, rather than using them concurrently.
HCV Pipeline links
Here's a couple :
http://www.hcvdrugs.com/
http://www.hcvadvocate.org/hepatitis/hepC/HCVDrugs.html
http://www.hepcstraightup.com/Whats_Next.htm
Roche megadose non-responder study
( I think Roche wants to capture as much of the non-responder market as possible before competitors butt in , and side-effects be damned ! )
TITAN Study: A Study of PEGASYS® (Peginterferon Alfa-2a (40KD)) Plus Copegus (Ribavirin) in Non-Responder Patients With Chronic Hepatitis C (CHC) Genotype 1
This study is not yet open for patient recruitment.
Sponsored by: Hoffmann-La Roche
Information provided by: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00412334
Purpose
This study will evaluate the efficacy and safety of 4 regimens of PEGASYS® plus Copegus, in patients with chronic hepatitis C (CHC) genotype 1 who have failed to respond to previous treatment with standard doses of PEGASYS® plus ribavirin. Patients will be randomized to one of 4 groups, to receive
a)PEGASYS® 360µg/week plus Copegus 1000-1200mg/day, b)PEGASYS® 180µg twice weekly plus Copegus 1000-1200mg/day, c)PEGASYS® 360µg/week plus Copegus 1200-1600mg/day, or d)PEGASYS® 180µg twice weekly plus Copegus 1200-1600mg/day. ( OUCH! )
Following 48 weeks treatment, there will be a 24 week period of treatment-free follow-up. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Good work on the RMF , go seek. Thanks !
Let's hope today's move is the start of a lasting trend. I'm anxiously awaiting the riba interaction data as I agree with dewophile that positive results could result in a favorable reevaluation of NM283 vs. VX950, with a nice effect on pps. I'd like to see a label that includes usage without riba as well , of course , but I think there is probably concern at the moment that good SVR rates are more likely if riba is in the mix somewhere. The lack of any disclosures about SVR in patients treated thus far is somewhat troubling , I must admit , but there may be good reasons for that. I just wish I knew what they were.
$9.50 tomorrow would be sweet.
>> On the other hand
cessation of heavy alcohol use has been found to increase brain
mass by 2% in 100 days, so there is hope for some of us. <<
So in a year I can do three cycles of heavy drinking followed by cessation , which should give me a 6% plus increase in brain mass after one year. Compounded , in 10 or 12 years I'll have double the brain mass. Now , in my case there's probably plenty of room up there to accomodate this increase , but others would need a bigger skull , no ?
Anyway , I'm gonna give it a go.
Re : DNDN
I see today's news as more positive than is reflected by the small pps increase , which IMO is a result of 'capping' efforts , based on the volume. I just can't believe many longs are unloading today because of a 15 cent pop , and I also can't see any good reason for new shorts to be jumping on board. The only explanation for the price action today that makes sense to me is further efforts by committed shorts trying to protect existing positions.
This article from Signals is a few years old , but it makes me think Priority Review is a meaningful event ( much moreso than Fast Track , though they're obviously related ) :
http://tinyurl.com/l1y9
"We grant Fast Track designation based on a reasonable potential that the product can meet an unmet medical need, and that can be based on animal data in some cases,” said the FDA’s Jenkins (director of the office of new drugs at the FDA’s Center for Drug Evaluation and Research (CDER). ) “Often, that potential never materializes.”
Further, Fast Track designation does not guarantee or even imply that a product will be reviewed faster than a traditional approval, although it is generally assumed that Fast Track products will be granted Priority Review once a BLA or NDA is filed. “Fast Track is a designation we give early on, based on potential,” explained Jenkins. “Priority Review is something we do only when the application comes in and a preliminary look at the data suggests the drug has actually demonstrated a therapeutic potential. Not all Fast Track drugs will get a Priority Review because they may not live up to their potential.”
>>> There has been much interest and growing scientific literature examining how lifestyle factors such as physical activity, education and social engagement may help build "cognitive reserve" in later years of life. <<<
I do crosswords , Sudoku , etc. and hope that it will help slow down the mental decline that I can already detect in myself , and I'd consider trying to learn a second language if I was really convinced that it would work. I have my doubts , though , about all of these studies since I'm not sure they've ruled out the possibility that the cognitive reserve is pre-existing in those people who are more likely to engage in such exercises ( " Those that can , do. " ). Thus , the activities that are believed to confer the protective effect are no more that surrogate markers for the lucky population with the built-in cognitive reserve.
This sort of cause-effect vs. association confusion is common in the popular science press and I rarely see articles that address this issue in a way that gives me any confidence in the conclusions. It's frustrating , since none of us has the time to chase down the original research every time to try to sort it out.
Anti-cancer chicken eggs produced
( The link under the goat pic is to an older article about GTCB.)
http://news.bbc.co.uk/2/hi/science/nature/6261427.stm
UK scientists have developed genetically modified chickens capable of laying eggs containing proteins needed to make cancer-fighting drugs.
The breakthrough has been announced by the same research centre that created the cloned sheep, Dolly.
The Roslin Institute, near Edinburgh, says it has produced five generations of birds that can produce useful levels of life-saving proteins in egg whites.
The work could lead to a range of drugs that are cheaper and easier to make.
Professor Harry Griffin, director of the institute, told the BBC: "One of the characteristics of lots of medical treatments these days is that they're very expensive.
"The idea of producing the proteins involved in treatments of flocks of laying hens means they can produce in bulk, they can produce cheaply and indeed the raw material for this production system is quite literally chicken feed."
Roslin has bred some 500 modified birds. Their existence is the result of more than 15 years' work by the lead scientist on the project, Dr Helen Sang.
But it could be another five years before patient trials get the go-ahead and 10 years until a medicine is fully developed, the Roslin Institute cautioned.
Anti-viral approach
Therapeutic proteins such as insulin have long been produced in bacteria; but there are some complex proteins that can only be made in the more sophisticated cells of larger organisms.
Scientists have successfully made a range of these molecules in the milk of genetically modified sheep, goats, cows and rabbits.
The work at Roslin shows it is now possible to use chickens as "biofactories", too.
A number of GM animals are now being used as drug factories
Some of the birds have been engineered to lay eggs that contain miR24, a type of antibody with potential for treating malignant melanoma, or skin cancer. Others produce human interferon b-1a, which can be used to stop viruses replicating in cells.
The proteins are secreted into the whites of the eggs. It is a fairly straightforward process then to extract and purify them.
Dr Sang said the team was highly encouraged by the level of the birds' productivity, but further improvements were required.
"We're probably getting a high enough productivity if you want to make a very active protein like interferon, but not enough yet if you want to make an antibody because people need large doses of these over long periods; so one of our next challenges is to try to increase the yield in egg white," she told BBC News.
Wider role
Chickens had some advantages over other animals for "pharming" because their lifecycles were shorter, said Dr Sang.
"Once you've made the transgenic birds, then it's very easy; once you've got the gene in, then you can breed up hundreds of birds from one cockerel - because they can be bred with hundreds of hens and you can collect an egg a day and have hundreds of chicks in no time," she explained.
The Roslin research is part of the Avian Transgenic Project, a joint venture with biotechnology firms Viragen and Oxford BioMedica.
Details of the latest work are to be published this week in the US journal Proceedings of the National Academy of Sciences (PNAS).
The Roslin team also expects its engineered chickens to provide new insights into aspects of reproductive biology.
It says the ability to modify birds' embryos will allow researchers to study fundamental processes that control the very early development of vertebrates.
It is just over 10 years since the Finn Dorset lamb called Dolly was born at the institute.
She was the first mammal to be cloned from an adult cell - making her a genetic replica of a six-year-old ewe. She was put down in 2003 after contracting a common lung disease.
Story from BBC NEWS:
Published: 2007/01/14 18:49:45 GMT
Court Permanently Halts Abbott's Sale of HCV Genotyping Products for Infringing Innogenetics' Patent
Jan 11 2007, 11:52 AM EST
GEN News Highlights
Innogenetics reported that a U.S. court entered a permanent injunction against Abbott Laboratories, prohibiting the company from selling or using products, including components, that infringe on Innogenetics' patented Hepatitis C Virus genotyping technology. The injunction also prevents Abbott from exporting components of the infringing products to foreign countries.
In September 2006 a jury unanimously found that Abbott had willfully infringed Innogenetics' U.S. patent 5,846,704 and awarded the company $7 million in damages.
The U.S. District Court for the Western District of Wisconsin made the ruling at the close of an evidentiary hearing to determine the potential public impact of a permanent injunction against Abbott. Last week, the court found that Innogenetics suffered irreparable harm from Abbott's infringement.
http://tinyurl.com/tbaek
Nice article on TLRs
Some interesting historical tidbits - mentions DVAX and COLY. ( click on the link to " Selected TLR Ligands in Clinical Trials " for a table of DVAX / COLY trials ) :
Deciphering Immunology's Dirty Secret
Can innate immune adjuvants save vaccinology?
By Kate Travis
http://www.the-scientist.com/2007/1/1/46/1/
>>> JP sounds like he has a terrible cold, coughing and sneezing. Might have been better for someone else to make the presentation? <<<
I agree. I can hear the wise guys in the crowd now : " What JP needs is a good antiviral. "
From one of the slides , it looks like entecavir captured around 15-20% of the total nuke scrips by the end of the first year of sales. I'd be happy if Tyzeka shows a similar trajectory , but I haven't tried to figure out what the first-year sales figure would be for that scenario. Probably over $20 mill. , but maybe not that much more considering we're talking mostly U.S. sales until ex-U.S. ramps up.
To get to $20 mill. first-year sales we may be selling at a $50 or $60 mill. annual rate or more by the end of that first year (U.S.).
Gl-5005 prelim results :
I don't remember if we commented on these results when they were presented at AASLD , but here's the PR anyway. Maybe Schiff is looking at it as a patient-friendly tx. with possible benefit on liver health ( evidenced by lower ALTs ) without having much expectation of achieving SVR. Or , he may know of patients that have continued to show viral load reduction beyond what is reported below and thinks that at least a few of them may achieve SVR eventually.
LOUISVILLE, CO – October 30, 2006 – GlobeImmune, Inc. today announced positive interim results from Study GI-5005-01, a randomized, placebo-controlled, multi-center, dose-escalation, Phase 1b study of GI-5005 in patients chronically infected with hepatitis C virus (HCV). The data were presented today at the annual meeting of the American Association for the Study of Liver Diseases (AASLD). GI-5005 generated cellular immune responses in 12/29 patients (41%), elicited a statistically significant improvement in alanine amino transferase (ALT) levels from baseline and caused near 1 log10 viral load reductions in three patients, two of whom had positive immune responses after only a three month course of GI-5005 monotherapy. No meaningful safety concerns were seen in the study to date.
“The interim results of this study appear to demonstrate a robust immunologic response in patients with chronic HCV,” said Timothy C. Rodell, M.D., GlobeImmune’s President and CEO. “To our knowledge, no other HCV therapy in development or on the market has shown the ability to convert the weak cellular immune response typically seen in chronically infected patients to a strong cellular response. The immune responses observed in chronically infected patients treated with GI-5005 resemble those of patients in the early stages of exposure to hepatitis C virus during which a proportion of patients can spontaneously cure themselves. This suggests that GI-5005 has the potential to transform the immune activity of chronically infected patients into a more effective response and drive favorable clinical outcomes in the setting of chronic hepatitis C disease.”
The purpose of the ongoing study is to evaluate the safety and preliminary efficacy of five weekly subcutaneous doses followed by two monthly subcutaneous doses of GI-5005 in ascending dose groups in patients chronically infected with hepatitis C virus. Patients that were treatment naïve, partial responders, or relapsers to an interferon-based regimen with or without ribavirin, were eligible for the study. Interim results on the first 40 subjects enrolled were presented in a poster at AASLD entitled: “Interim Results from a Randomized, Double-blind, Placebo-controlled Phase 1b Study in Subjects with Chronic HCV after Treatment with GI-5005, a Yeast-Based HCV Immunotherapy Targeting NS3 and Core Proteins.”
The preliminary results of the study to date have demonstrated:
1) GI-5005 is well tolerated with no serious adverse events (SAEs), dose limiting toxicities (DLTs), and no discontinuations due to adverse events (AEs) to date.
2) GI-5005 converted subjects with a weak cellular immune response typical of chronic HCV patients to a strong cellular immune response with broad HCV epitope coverage, consistent with the immune response seen in patients during the acute stage of infection.
3) The immune responses were observed in association with favorable changes in viral load and ALT:
a. A statistically significant difference in maximum change in ALT (a surrogate of hepatic injury) from baseline in all GI-5005 treated subjects compared to placebo treated subjects (p=0.03).
b. Three treated patients had viral load reductions approaching 1 log10 (0.75 log10 – 0.90 log10); no placebo patients had HCV RNA reductions > 0.65 log10.
http://tinyurl.com/y236rd
Re : Globeimmune trial
Like dewophile I would think the Prove 3 trial would offer a better chance of a successful outcome , though I don't know much about GI-5005 and Schiff presumably does.
One thing to look at to help you decide -- the enrollment rates of the trials , as a means to weigh the perceptions of the medical / patient community about the tx. in question. VRTX will enroll hundreds of patients for Prove 3 in a matter of months , while it looks like the Globeimmune trial has been enrolling since '05 to get 48 patients. Enrollment criteria and other factors can influence this , of course , so it's not foolproof.
Re: SCLN
>>> I think this is a product/company worth keeping an eye on. <<<
dewophile,
Good advice. Keep one eye on the company and the other on your money. I briefly took my eye off SCLN once and all my money disappeared !
I wish I could say I was just kidding. Still , I'm pulling for SCLN to succeed in the melanoma indication , though I only have a token position in them now.
The recent survival results would look more robust to me if I didn't know the sordid history of SCLN "results". I'd wait to see more details before placing a big bet on this data release. The thing that concerns me about this particular dataset is that it's so sensitive to the validity of the single control arm results , and the fact that the best treatment regimen ( Z plus DTIC , no interferon ) had no comparable control arm. Also , the pending high-dose results are from a regimen including interferon , when it seems likely that better results would be expected if ifn had been omitted.
The thing to hope for , IMO , is that some pretreatment variable or biomarker is predictive of treatment response , which would reduce the size of the P3 trial(s) and raise the odds for a successful outcome.
>> CORT up 40% Why? Results from Corlux trial? <<
I can't find anything.
Leaks ?
ARIA update
(I just came across this. Anyone betting that ARIA will prevail against Lilly and that their broad patent claims will be upheld is taking a huge risk , IMO.)
Court Stays Amgen Suit Against Ariad Pending Appeal
12/21/2006
Dow Jones News Services
(Copyright © 2006 Dow Jones & Company, Inc.)
By Peg Brickley
Of DOW JONES NEWSWIRES
A federal magistrate judge on Thursday called a halt to the action in Amgen Inc.'s (AMGN) lawsuit against Ariad Pharmaceuticals Inc. (ARIA) until a federal appeals court rules on whether the case can go forward.
The one-page ruling from U.S. Magistrate Judge Mary Pat Thynge is a small victory for Ariad, which said Amgen's legal challenge to the validity of one of its patents is draining its scarce financial resources.
The ruling means no more papers can be traded in a Delaware federal trial court until a patent appeals panel in Washington weighs the question of whether Amgen, which has a market capitalization of about $82 billion, has reason to fear Ariad, which has a market capitalization of about $296 million.
Thousand Oaks, Calif.-based Amgen sued Ariad in April in federal court in Delaware, seeking to invalidate a patent that Ariad might be able to use against Amgen's Enbrel and Kineret arthritis treatments.
Such suits are permissible when a company with a product on the market has reason to believe it could be accused of patent infringement and wants to make sure it's in the clear.
A federal judge in Delaware sided with Amgen and refused to dismiss the lawsuit. U.S. District Judge Kent Jordan gave Ariad permission to appeal his ruling immediately to the U.S. Court of Appeals for the Federal Circuit.
A win by Ariad in the appeals court could end the case completely. A win for Amgen means pretrial action will resume in Delaware.
"Amgen filed suit simply because it seeks a judicial resolution on the issue, i.e., that Amgen does not owe royalties under the '516 patent for Enbrel and Kineret. Amgen is working appropriately within the legal system to resolve this issue," Amgen spokesman David Polk said in a statement before Thursday's decision to stay the case.
Ariad has not sued Amgen for patent infringement and said in court papers it just wants to be left alone to work on its promising cancer treatment.
Patient enrollments are slated to begin in the first quarter of 2007 for late-stage clinical trials of Ariad's AP23573, a sarcoma treatment that also may be effective against prostate and endometrial cancer.
In court papers, Ariad said it had $39 million in cash, is burning about $15 million each quarter, and has no time or money for a legal fight with Amgen.
"This case is a prime example in which Ariad's financial well-being and the public interest may be dictated by whether or not this litigation proceeds," Ariad's attorneys wrote.
Court papers Amgen filed in reply said the little Cambridge, Mass., biotechnology company has spent heavily to wield its patents against big drug maker Eli Lilly & Co. (LLY). Therefore, Ariad's financial situation should not prevent Amgen from getting its day in court to safeguard its Enbrel and Kineret rights.
In May, a federal court jury in Boston told Eli Lilly to pay Ariad and several academic institutions $65.2 million in a patent infringement action involving Lilly's osteoporosis drug Evista and septic-shock drug Xigris.
Lilly appealed.
Separately, a federal patent agency decision cast a shadow on Ariad's chances of collecting on the judgment. In September, the U.S. Patent and Trademark Office tentatively rejected about 160 claims in the patent Ariad used against Lilly, leaving only a portion of the patent standing.
Ariad has challenged the Patent Office's decision, which threatens to upset its claim to own wide-ranging rights to cell-signaling pathways.
-By Peg Brickley, Dow Jones Newswires; 302-521-2266; peg.brickley@dowjones.com
http://tinyurl.com/u64ws
Re:COLY,ANDS,etc.--Article on TLRs in Science
( On one hand , this article suggests that some current TLR research might be misdirected. On the other hand , it would seem to strengthen the case of the TLR companies against the claims of Ariad , who says they own rights to all drugs that target the NF-kappaB pathway.)
Science 22 December 2006:
Vol. 314. no. 5807, pp. 1936 - 1938
Adjuvant-Enhanced Antibody Responses in the Absence of Toll-Like Receptor Signaling
Amanda L. Gavin,1 Kasper Hoebe,1 Bao Duong,1,2 Takayuki Ota,1 Christopher Martin,1,2 Bruce Beutler,1 David Nemazee1*
Innate immune signals mediated by Toll-like receptors (TLRs) have been thought to contribute considerably to the antibody-enhancing effects of vaccine adjuvants. However, we report here that mice deficient in the critical signaling components for TLR mount robust antibody responses to T cell–dependent antigen given in four typical adjuvants: alum, Freund's complete adjuvant, Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate adjuvant. We conclude that TLR signaling does not account for the action of classical adjuvants and does not fully explain the action of a strong adjuvant containing a TLR ligand. This may have important implications in the use and development of vaccine adjuvants.
1 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037 USA.
2 The Scripps Research Institute, Kellogg School of Science and Technology, Doctoral Program in Chemical and Biological Sciences, La Jolla, CA 92037, USA
http://tinyurl.com/ykuoj6
>>> I’ll be on semi-vacation status next week ...<<<
That's good. I hope you enjoy some well-deserved semi-relaxation.
Or semi-enjoy , at least.
Happy Holidays , all !!
http://tinyurl.com/yys8ff
>>> I’ve gone running outdoors in a T-shirt and shorts four times in the past week and a half, and this evening will make five. <<<
Leave the shorts at home tonite and then we can all watch you on the evening news.
>>> The one negative side effect of Proellex and Androxal is investment-related alopecia, and I need time and expensive hair-care products to recuperate. <<<
Just remember to get a baseline PSA before you start on the Propecia.
>> The FDA allows HIV investigational compounds to be tested with each other for treatment resistant patients, why not for HCV? <<
My thoughts exactly. Let's get on with it , for crying out loud !
Dew recently suggested that companies may be reluctant to run these combo studies for fear of tainting the reputation of their drug with some other drug's nasty AEs , so this might also contribute to the problem. Still , as you said , the HIV model is there and the need is there for HCV nonresponders in particular , so I don't understand what's the holdup.
>> my recollection re "creative" strategies however was to try and get higher doses of NM-283 on board and work around the GI issues. <<
When this topic was first discussed here Dew and I had different interpretations about what IDIX was referring to when they mentioned the "creative strategies" thing. My impression was that they were looking for ways to target nonresponders using NM283 , but not necessarily restricted to ways to deal with the dosing / GI issues. I'm not sure we ever resolved this and it's probably not important that we do , since all we're doing is having some fun tossing out hypothetical solutions to a problem that's poorly defined , which only adds to the fun.
I just hope they come up with something that actually sounds creative , otherwise we'll all be disappointed. For example , a combo treatment of NM283 plus Tums would not be creative enough ,IMO.
Thalidomide ( or, possibly , Revlimid ) , is one of those things that is much more likely to be explored overseas than here , for obvious reasons , but the results on those six nonresponders is compelling and it makes me wonder what's going on there. The immune modulating effects of thalidomide might work in many antiviral / antitumor immunotherapy settings. The downside is that during treatment all patients must wear a chastity belt.
I hadn't thought of a ritonavir boost type approach but that's a good idea as a way to reduce GI exposure. We just need to figure out what agent to use.
re : "Creative ideas" on the NM283 (higher dosage) refractory end?
The most intriguing thing I've seen lately is the use of thalidomide in combo with SOC in nonresponders. It seems that the thalidomide is acting mainly as an immunomodulator rather than a direct antiviral , so it might be able to replace riba and / or ifn when combined with a potent direct antiviral. Don't ask me how IDIX would set up a trial to explore this , though.
...
Report of 6 Cases of Complete HCV Remission in Prior Non-Responders Treated with Pegylated Interferon Plus Ribavirin Plus Thalidomide
( Note : This report also lists some of the other experimental treatments that have been tried in nonresponders )
http://www.hivandhepatitis.com/hep_c/news/2006/120806_a.html
...
Thalidomide: An old drug may represent a novel weapon against hepatitis C
http://www.asm.org/Media/index.asp?bid=39253
Who is : Guy Macdonald – Executive Vice President, Operations
@ Idenix
InterMune Initiates Phase 1a Clinical Trial Evaluating Hepatitis C Protease Inhibitor ITMN-191 in Collaboration with Roche
Tuesday December 19, 12:40 pm ET
BRISBANE, Calif., Dec. 19 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN - News) announced today that the company and its partner Roche have received approval of the European Clinical Trial Authorization (CTA) for ITMN-191, the NS3/4A protease inhibitor, and have initiated a Phase 1a clinical trial evaluating ITMN-191 for the treatment of chronic hepatitis C virus (HCV) infection. The Phase 1a trial will assess safety, tolerability, pharmacokinetics and food affect in a double-blind, placebo-controlled single ascending dose study. The study is being conducted at one clinical trial site in Europe and will enroll approximately 74 healthy volunteers. InterMune expects to dose the first patient with ITMN-191 sometime in early January 2007.
"Our preclinical research indicates ITMN-191 has the potential to be an important addition to therapy for HCV patients because of its favorable cross resistance and potency profiles, as well as pharmacokinetic results that support the exploration of twice-daily oral dosing in future clinical trials," said Lawrence M. Blatt, Ph.D., Chief Scientific Officer of InterMune. "The initiation of the Phase 1a human trial for ITMN-191 moves our HCV protease inhibitor program one step closer to the proof-of-concept Phase 1b clinical study in patients infected with HCV. We look forward to providing updates as we advance the program with our partner Roche."
http://tinyurl.com/y2xsbq