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Isis Pharmaceuticals, Inc. Message Board

  • darkouttonight darkouttonight Jun 14, 2010 8:57 AM Flag

    One Fatal antisense drug Flaw.

    The main problem with antisense drug technology is that man and animals have naturally occurring enzymes within the serum, called nucleases, which degrade oligos or DNA. When introduced into the body, normal DNA is not the ideal antisense agent because it readily undergoes antisense digestion! Many attempts have been made to avoid this problem. By avoiding this problem, it has led to other serious problems. What antisense PhDs came up with was phosphorothioates which become associated with serum proteins. Serum proteins prevent rapid clearance by the kidneys. Distribution of material from the blood to the tissue occurs very rapidly, with plasma half-life on the order of less than one hour. Isis was able to extend this process but not nearly enough (no matter what they say). Even with Isis generation 2.5 increased specificity and stability it's not enough. Distribution is still broadly into all tissues, with the highest percentage of the dose to the LIVER, KIDNEY, and BONE MARROW! Now how did I know the result of the last Mipo data two years ahead of the Isis press release in early February 2010? COMMON SENSE!

    Don't look for these facts on the IV huckster board. That phoney board didn't like the truth. (I was too negative.) Contrary to all the BS on the IV wannabe board and this board, Dr. Crooke can't hold a candle to Paul Zamecnik who received the 1996 Lasker award for outstanding contribution to antisense science and medicine.

    I do have to give credit to the little guy for being a super-saleman bringing in the money to keep the hope going. Thus, he has a lifetime job for himself and other insiders and who else he wants to drag along. No, not you long-suffering geniuses!

    I suggest that you invest in a little-known vaccine company called Vical.

    Oh yes, one more item of interest... Barclays & several other financial advisors paid huge amounts of money over the years to be guided in the right direction for their clients. In the end, they paid for poor advise and ignored mine for free. Chuckle

    Did you say Poughkeepsie, NY? Chuckle with a chortle. 8:)

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    • This dark post on june 14-10 saved me.

      • 2 Replies to nycknowsbest
      • nycknowsnothing,

        You've been a know nothing Dark supporter since July of 2009 yet you say that "[t]his dark post on june 14-10 saved me."

        Could you please take your nose out of Dark's a** for one minute and explain how that particular post by Dark "saved" you?

        (And is that really the best you can do to try and put a gloss of legitimacy on what has been revealed to be utter Dark nonsense? Pathetic.)

      • What is Dark Jesus Christ now? We don't need saving.
        We need balanced truthful messages. Not half-truthful, slanted, bogus, idiotic crap about antisense technology not working!

        I ask once again, as I have never received an answer:
        WHAT are Dark's credentials?
        Other than being some know-it-all neophyte smalltime investor who THINKS he is competant to teach us all about antisense technology.

        I'm waiting for an answer!

    • Outinfront,

      That's a great argument that ISIS is a bad investment. But the claim Dark is making is that ISIS antisense is "fatally flawed." He grandly proclaimed he would make a "presentation" in June to prove it. Now Dark has the burden to back up his claim about the science of antisense. Since his "presentation" did nothing of the kind, he has opened himself to deserved criticism and ridicule. His obfuscations and evasions in this regard are clear.

      ISIS may be a terrible investment but Dark's constant repetition that the science is "fatally flawed" greatly undercuts his credibility.

      I 4 I

    • You suggest that world leaders in science and clinical treatment of suffering patients are wasting their time on ANS drug development. You go further and claim these leaders take millions in government and investor dollars and p**s away their God-given talents playing around with ANS drugs, so they can live the good life. Isn't that cynical? Isn't it plain silly?

      Take OGXI and 011 in prostate and lung cancer. In phase II, this ANS drug had same efficacy as Mipo, and there were no observable safety concerns, indeed, in cancer, the side effects Dark noted are irrelevant, since cancer is not a chronic treatment.

      ANS is not dead. It is alive. Reserve your judgments until the facts are known. Isn't that science?

      • 1 Reply to dr.kuvasz
      • Kuvasz,

        Please don't mislead people on this board by placing sooooo many words such as "suggest" in my mouth. When you state the antisense "side effects are irrelevant",It takes away from your credibility and makes you not only silly but dark cynical. I suggest that you study up on the subject by requesting information as to why at least ten huge pharmas have left collaborations with Isis. Notice, that I didn't mention many of the universities. I don't have the time to convince you against your will... good luck ! :>)

        I just glanced at a posters message with regard to Vical's ten year old data on A-7. Again, I don't have the time to answer every nit-wit genius. I'm only here to protect the newbies. BTW, I'd love to go into depth with Vical as there are some very interesting late-stage clinical trials wrapping up data capturing. Check on the SNY & AnGes if you have a chance. Have a great day everyone! :>)

    • from your june 14 report:

      " Even with Isis generation 2.5 increased specificity and stability it's not enough. Distribution is still broadly into all tissues, with the highest percentage of the dose to the LIVER, KIDNEY, and BONE MARROW! Now how did I know the result of the last Mipo data two years ahead of the Isis press release in early February 2010? COMMON SENSE

      Come on dark.. COMMON SENSE won't do in science. Where are these facts from????

    • Please read my post of June-14-2010 8:57 A.M.

      The useless IV board has done their huckster damage as usual. At least a few of you were saved. :>) Oh well. zzzzzzzzzzz

    • Darkster did focus on the future with this isis antisense post.

    • You are lying there NYy those "ladies" in the IR Dept. know a lot more than you'll ever know. You really didn't call them, or you're embarrassed in the fact they knew a lot more about ANS than you do. They all have PhD's or have worked at ISIS for more than 15 years. Why not go and find some Russian or Chinese company or something to harass? t

    • No wonder repetative questions to darkout.

      with out engagement.

    • Dark:

      I'm still waiting for you to answer some simple questions:

      1. On June 14, 2010, you changed your view on ISIS saying it was now an "Offical [sic] $8.75 to $9 HOLD." You said you would explain later why you made this change but still haven't done so. Why did you make the change from "Sell" to "Hold?"

      2. Also, on June 14, 2010, I asked you the following, "Given that you have raised ISIS to a hold at the $8.75-$9 level, and given that ISIS is currently trading above $9.50, what do you suggest investors do right here? Buy, sell or hold?" You still haven't responded to this simple question, why?

      3. On June 14, 2010, you posted what you claimed was one of Antisense's "fatal flaws." How many "fatal flaws" do you claim exist? Do you plan on posting what these "fatal flaws" are? If so, When?

      4. In your June 14, 2010 post, you referenced Paul Zamecnik saying "Dr. Crooke can't hold a candle to Paul Zamecnik." Did Paul Zamecnik contradict the view of Crooke with regard to antisense in some fundamental way that supports your critique of ISIS? If so, what did he say and where did he say it?

      Finally, I will note that if your true motivation in posting on this ISIS board is to protect newbies from being suckered by the ISIS pr machine, you would answer simple questions posed to you that directly relate to the substance of your posts. Obviously, there is a lot of controversy regarding ISIS. You have been a long time ISIS bear but many readers of this board assert that you are simply a disgruntled former employee who pathologically attacks ISIS antisense technology without a real understanding of the technology involved. Your continuing failure to answer simple, relevant and fair questions will go a long way in providing newbies with a reasonable basis to evaluate your dire warnings. Every day you refuse to answer these simple questions (forthrightly and honestly), the verdict about you becomes clearer and clearer.

      I 4 I

    • Way to go darkout!

      • 1 Reply to theworldisonfire8
      • Theworldisonfire8:

        I fully expect that Dark will provide some real meat and substance in support of his anti-Isis position. But don't you think it is just a little over the top to give the man a medal for that first post? I would imagine that even Dark agrees he does not deserve effusive praise for that post. I'll be real disappointed if that post wasn't merely an appetizer and the main course has yet to be served.

        (Dark, please don't disappoint. I would like nothing better for you to be able to convince me that ISIS is a bad investment. If you do that you may well save me from losing a lot of money. And that is why I intend to keep an open mind to what you have to say. Till then I remain a bull on ISIS.)

        I 4 I

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