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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?

To: Bluegreen who wrote (6706)	7/17/1998 10:17:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Bluegreen, not about LBP but one of the acquired patents. I would appreciate any post that help make this patent more understandable. 5532216 : Neutralization of non-lipopolysaccharide compounds by bactericidal/permeability-increasing protein 13 CLAIMS We claim: 1. A method of inhibiting mannuronic acid polymer-mediated stimulation of host inflammatory cells in the presence of a cell-stimulating amount of a mannuronic acid polymer, said method comprising administering to the host bactericidal/permeability-increasing protein (BPI) in an amount effective to inhibit inflammatory cell stimulation. 2. The method of claim 1 wherein the mannuronic acid polymer comprises a gel having encapsulated therein living implant cells, and an effective amount of BPI to inhibit stimulation of said inflammatory cell by said gel, said effective amount being from about 1% to 100% by weight of the mannuronic acid polymer. 3. The method of claim 2 wherein the gel encapsulated cells are hormone-producing cells. 4. The method of claim 3 wherein the hormone-producing cells and the BPI are administered together in a single composition or separate compositions. 5. The method of claim 3 wherein the hormone-producing cells are pancreatic islet cells. 6. A method of inhibiting mannuronic acid polymer-mediated tumor necrosis factor (TNF), IL-1 or IL-6 production by human host mononuclear cells in the presence of a cell-stimulating amount of a mannuronic acid polymer, which comprises administering to a host bactericidal/permeability-increasing protein in an amount effective to inhibit TNF, IL-1 or IL-6 production. 7. The method of claim 6 wherein the mannuronic acid polymer comprises a gel having encapsulated therein living cells and an effective amount of a BPI to inhibit stimulation of said cells by said gel, said effective amount of BPI being from about 1% to 100% by weight of the mannuronic acid polymer. 8. A composition comprising a mannuronic acid polymer and an effective amount of a bactericidal/permeability-increasing protein (BPI) to inhibit inflammatory cell stimulation by said mannuronic acid polymer, and optionally a physiologically or pharmaceutically acceptable carrier. 9. The composition of claim 8 wherein said mannuronic acid polymer is a gel having encapsulated therein living cells. 10. The composition of claim 8, wherein said effective amount is from about 1% to 100% by weight of the mannuronic acid polymer. 11. A method for preparing an encapsulated living cell composition substantially-free of inflammatory cell stimulation activity, which comprises (a) encapsulating living cells in a mannuronic acid polymer gel and (b) admixing said gel with a bactericidal/permeability-increasing protein (BPI) optionally with a physiologically or pharmaceutically acceptable carrier. 12. A kit for administration of a mannuronic acid polymer substantially free of inflammatory cell stimulation activity comprising (a) a bactericidal/permeability-increasing protein (BPI) and (b) a mannuronic acid polymer, wherein said (a) and (b) can be administered together or separately. 13. The kit of claim 12 wherein said mannuronic acid polymer has encapsulated therein living cells.

To: Bluegreen who wrote (6706)	7/17/1998 11:22:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Bluegreen, here are the magnificent 7. 1. 5,770,694 Genetically engineered BPI variant proteins 2. 5,532,216 Neutralization of non-lipopolysaccharide compounds by bactericidal/permeability-increasing protein 3. 5,334,584 Recombinant, non-glycosylated bpi protein and uses thereof 4. 5,308,834 Treatment of endotoxin-associated shock and prevention thereof using a BPI protein 5. 5,234,912 Pharmaceutical compositions comprising recombinant BPI proteins and a lipid carrier and uses thereof 6. 5,171,739 Treatment of endotoxin-associated shock and preventation thereof using a BPI protein 7. 5,089,274 Use of bactericidal/permeability increasing protein or biologically active analogs thereof to treat endotoxin-related disorders

To: Bluegreen who wrote (6706)	7/18/1998 12:12:00 AM
From: Robert K.	Respond to of 17367

Lbp-lets start with 5731415 (my favorite)>>>>>>>>>>>>>>>>>>>>>>.. >I think its lbp/bpi/lbp> (and varients on this idea) Start cd14 regulates inflamation via IL-1,IL-6,IL-8, & TNF lbp turns it on.......and you get inflamation bpi blocks lbp from cd14.......and you DONT get inflamation Its more complex than above, but thats the simple answer (as I know it) Ok so far....... bpi is a cellular protein and has a short half lide life in plasma bpi21 is a extended half life version of the active part of bpi. OK so far..... Now lbp is a plasma protein (it naturally is in plasma) It has a LONG half life in plasma BUT it causes inflamation when attached to LPS via cd14 Now here comes lbp/bpi/lbp>>> no cd14 stimulation,no inflamation Now if you add lbp to bpi you get increased bacteria killing (up to 10,000 fold) (horowitz 1995) Above contain many concepts but let me point to just a few. 1. lbp derivative might potentiate without inflamation 2. lbp derivative might stop inflamation (helps bpi) (arthiritis,sepsis,cascade etc) (any inflamatory disorder mediated by lps type bacteria) 3. lbp derivative might greatly extend bpi half life(bpi/lbp/bpi) 4. lbp derivative blocks real lbp from cd14>no inflamation We are talking inflamation control (from bacteria) at the SOURCE We are talking better bpi killing of bacteria Hows that for starters. yes there is much more, but those are the basic concepts I am willing to explain for now. Remember this>this is cutting edge research, even the experts dont understand it. How do you expect the wall street types to get it. You see>>>>>>>They DONT GET IT. >YET. .5,770,561 Method for potentiating BPI protein product bactericidal activity by administration of LBP protein products 2.5,731,415 Lipopolysaccharide binding protein derivatives 3.5,484,705 Method for quantifying lipopolysaccharide binding protein 4.5,466,581 Method for quantifying BPI in body fluids 5.5,466,580 Method for quantifying BPI in body fluids >ALL IMO Preview Use Fixed Font....Terms of UseYou are responding to this message from Bluegreen on Jul 17 1998 4:24PM EST RobertK, you state you are going to talk more about LBP. I assume you are talking about the LBP derivative that Xoma has in its patent portfolio. Can this LBP be attached to rBPI21 or will it have to be given separately?

To: Bluegreen who wrote (6706)	7/18/1998 10:50:00 AM
From: aknahow	Respond to of 17367

Bluegreen, what follow is of interest only because of mention of ENP. Undated INCY research on BPI. Assume it's old but note ENP. A COMPARISON OF A RECOMBINANT ENDOTOXIN NEUTRALIZING PROTEIN VERSUS A RECOMBINANT BACTERICIDAL/PERMEABILITY INCREASING PROTEIN VARIANT FOR THE TREATMENT OF E. COLI SEPSIS IN THE RAT Anne M. Stack, Richard A. Saladino, Marian N. Marra, Thomas Novitsky, George R. Siber, Gary R. Fleisher,Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, and Associates of Cape Cod, Woods Hole, Massachusetts, and Incyte Pharmaceuticals, Inc., Palo Alto, California. Considerable effort has been directed toward neutralization of endotoxin for the treatment of gram-negative sepsis. Objective: An 11.8-kDa recombinant endotoxin neutralizing protein (ENP) from Limulus polyphemus and a 55-kDa recombinant bactericidal/permeability increasing protein variant {BPI(NCY 118)} were compared in a randomized, blinded, controlled study using a rat model of Escherichia coli sepsis. Methods: An inoculum of 5.6 - 6.9 10 E. coli O18ac K1 in a gelatin capsule was implanted in the peritoneum of 200 - =n - 250-g male Wistar rats. An hour after E. coli challenge, blood was sampled for bacterial quantitation, lead acetate (30 mg/ kg), which sensitizes rats to the effects of endotoxin, and either ENP (50 mg/kg), BPI variant (20 mg/kg), or saline were administered intravenously. All animals received ceftriaxone (100 mg/kg) and gentamicin (5 mg/kg) intramuscularly immediately after treatment. Results: 94% of the animals had detectable bacteremia after one hour. E. coli sepsis with high mortality despite antibiotic therapy, ENP and BPI variants improved survival. ENP was superior to BPI variant in its protection at the doses tested, which are not molar equivalents. Results suggest that both ENP and BPI variant may be useful in the treatment for human gram-negative

To: Bluegreen who wrote (6706)	7/18/1998 5:56:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Bluegreen, hope you are not a hooligan. Some of the hooligans on another thread think XOMA is wrong about BPI working. Wonder why INCY claims it works? See 20 of the 25 claims listed below. 5089274 : Use of bactericidal/permeability increasing protein or biologically active analogs thereof to treat endotoxin-related disorders 25 CLAIMS What is claimed is: 1. A method of inhibiting the pyrogenic activity of an endotoxin which comprises contacting the endotoxin with an amount of Bactericidal/Permeability Increasing Protein effective to inhibit the pyrogenic activity of the endotoxin. 2. A method of inhibiting lipopolysaccharide-mediated tumor necrosis factor production by human mononuclear cells which comprises contacting LPS with Bactericidal/Permeability Increasing Protein in an amount effective to inhibit lipopolysaccharide-mediated tumor necrosis factor production by the mononuclear cells. 3. A method of inhibiting endotoxin-mediated stimulation of neutrophils or mononuclear cells which comprises contacting endotoxin-associated lipopolysaccharide (LPS) with a purified, endotoxin-free human Bactericidal/Permeability Increasing Protein (BPI) under conditions such that the BPI binds to endotoxin-associated LPS and thereby inhibits endotoxin-mediated stimulation of neutrophils or mononuclear cells. 4. A method of treating a subject suffering from a disorder selected from the group consisting of endotoxin-related shock, endotoxin-related disseminated intravascular coagulation, endotoxin-related anemia, endotoxin-related thrombocytopenia, endotoxin-related adult respiratory distress syndrome, and endotoxin-related renal failure which comprises administering to the subject a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and thereby inhibits lipopolysaccharide stimulation of neutrophils and mononuclear cells so as to thereby treat the subject. 5. A method of claim 4, wherein the disorder is endotoxin-related, disseminated intravascular coagulation. 6. A method of claim 4, wherein the disorder is endotoxin-related anemia. 7. A method of claim 4, wherein the disorder is endotoxin-related leukopenia. 8. A method of claim 4, wherein the disorder is endotoxin-related thrombocytopenia. 9. A method of claim 4, wherein the disorder is endotoxin-related adult respiratory distress syndrome. 10. A method of claim 4, wherein the disorder is endotoxin-related renal failure. 11. A method of treating a subject suffering from endotoxin-related shock which comprises administering to the subject a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and inhibits endotoxin-related shock so as to thereby treat the subject. 12. A method of reducing the symptoms associated with a disorder which comprises administering to a subject in need thereof purified, endotoxin-free Bactericidal/Permeability Increasing Protein under conditions such that the Bactericidal/Permeability Increasing Protein binds to endotoxin-associated lipopolysaccharide and inhibits lipopolysaccharide stimulation of neutrophils and mononuclear cells so as to thereby reduce the symptoms associated with the disorder, the disorder being selected from the group consisting of endotoxin-related shock, endotoxin-related disseminated intravascular coagulation, endotoxin-related anemia, endotoxin-related leukopenia, endotoxin-related thrombocytopenia, endotoxin-related adult respiratory distress syndrome, and endotoxin-related renal failure. 13. A method of claim 12, wherein the disorder is endotoxin-related shock. 14. A method of claim 12, wherein the disorder is endotoxin-related, disseminated intravascular coagulation. 15. A method of claim 12, wherein the disorder is endotoxin-related anemia. 16. A method of claim 12, wherein the disorder is endotoxin-related leukopenia. 17. A method of claim 12, wherein the disorder is endotoxin-related thrombocytopenia. 18. A method of claim 12, wherein the disorder is endotoxin-related adult respiratory distress syndrome. 19. A method of claim 12, wherein the disorder is endotoxin-related renal failure. 20. A method of recovering a purified, endotoxin-free, human Bactericidal/Permeability Increasing Protein having enhanced activity to inhibit endotoxin-mediated stimulatio