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Post by daduke38 on Aug 14, 2014 16:55:18 GMT -5
Isn't it true that MNKD has the patent on the combination of Lantus with "A". So in theory, wouldn't the marketing of Lantus with "A" extend the patent of Lantus if used with "A"? If that is the case, wouldn't MNKD have a right to be compensated to a degree for Lantus after the patent runs out? And could Lantus be administered eventally by technosphere or would it cause it to be too fast acting?
Am I reaching here?
And, I will say it one more time. Yes, Al did seem off to me, maybe just my perception. I remember my Dad and Grandfather starting to slip at that age, so maybe I was over sensitive to it. He could have been tired, stressed, or I might have mis-read it. No matter how this works out from a financial angle for me, I will always think of his achievements and legacy as one of the "Greats" of our era. If I gave a different perception, I apologize. And I certainly did not mean to imply the deal could of been better based on Al's perceived health.
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Post by dreamboatcruise on Aug 14, 2014 18:11:01 GMT -5
Isn't it true that MNKD has the patent on the combination of Lantus with "A". So in theory, wouldn't the marketing of Lantus with "A" extend the patent of Lantus if used with "A"? If that is the case, wouldn't MNKD have a right to be compensated to a degree for Lantus after the patent runs out? And could Lantus be administered eventally by technosphere or would it cause it to be too fast acting? Am I reaching here? And, I will say it one more time. Yes, Al did seem off to me, maybe just my perception. I remember my Dad and Grandfather starting to slip at that age, so maybe I was over sensitive to it. He could have been tired, stressed, or I might have mis-read it. No matter how this works out from a financial angle for me, I will always think of his achievements and legacy as one of the "Greats" of our era. If I gave a different perception, I apologize. And I certainly did not mean to imply the deal could of been better based on Al's perceived health. A quick look at what is covered by the patent, it would appear to cover best practice dosing for a "ultra rapid acting" insulin with Lantus... but the Lantus is still a separate daily dose. I'm sure that this would be what Sanofi is going to promote, so I would find it hard to believe that there would be extra payments associated with it that weren't disclosed. I would be willing to bet that when the full agreement is disclosed three months from now you'll see that MNKD is providing Sanofi the rights to use the covered intellectual property as part of the already disclosed financial arrangement. As for inhaled Lantus, I don't remember hearing any speculation about that. Apparently the long acting nature of it is due to a pH change when it gets injected... "when a physiologic pH (approximately 7.4) is achieved the increase in pH causes the insulin to come out of solution resulting in the formation of higher order aggregates of insulin hexamers" These then take time to disassociate into usable insulin monomers. The lungs do provide the same non-acidic pH, but whether this process would remain the same when Technospheres are inhaled is an interesting question. |
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Post by zieg on Aug 14, 2014 18:27:21 GMT -5
Isn't it true that MNKD has the patent on the combination of Lantus with "A". So in theory, wouldn't the marketing of Lantus with "A" extend the patent of Lantus if used with "A"? If that is the case, wouldn't MNKD have a right to be compensated to a degree for Lantus after the patent runs out? And could Lantus be administered eventally by technosphere or would it cause it to be too fast acting? Am I reaching here? And, I will say it one more time. Yes, Al did seem off to me, maybe just my perception. I remember my Dad and Grandfather starting to slip at that age, so maybe I was over sensitive to it. He could have been tired, stressed, or I might have mis-read it. No matter how this works out from a financial angle for me, I will always think of his achievements and legacy as one of the "Greats" of our era. If I gave a different perception, I apologize. And I certainly did not mean to imply the deal could of been better based on Al's perceived health. I think that if we are asking for a "piece" of the Lantus Afrezza combo, they could do the same vice versa. Kind of a chicken and an egg situation. With regards to Al, I can only imagine how tired he must have been to be on a conf call at 5:30 am West Coast time. How much sleep do you think he go the night before? I saw the press release Sun Eve at 1:14am and started emailing all MNKD friends that I knew would want to listen in the next morning. I was exhausted With Al, his 10 year culmination was coming to fruition. Maybe he was hung over from the jubilance of the previous night. We all know and love him for his passion and commitment. He's kind of like the wacky/cool Uncle that says stuff at the dinner table that the kids don't understand and the parents view as inappropriate. Good Luck All Longs!! |
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Post by daduke38 on Aug 14, 2014 20:21:20 GMT -5
Isn't it true that MNKD has the patent on the combination of Lantus with "A". So in theory, wouldn't the marketing of Lantus with "A" extend the patent of Lantus if used with "A"? If that is the case, wouldn't MNKD have a right to be compensated to a degree for Lantus after the patent runs out? And could Lantus be administered eventally by technosphere or would it cause it to be too fast acting? Am I reaching here? And, I will say it one more time. Yes, Al did seem off to me, maybe just my perception. I remember my Dad and Grandfather starting to slip at that age, so maybe I was over sensitive to it. He could have been tired, stressed, or I might have mis-read it. No matter how this works out from a financial angle for me, I will always think of his achievements and legacy as one of the "Greats" of our era. If I gave a different perception, I apologize. And I certainly did not mean to imply the deal could of been better based on Al's perceived health. A quick look at what is covered by the patent, it would appear to cover best practice dosing for a "ultra rapid acting" insulin with Lantus... but the Lantus is still a separate daily dose. I'm sure that this would be what Sanofi is going to promote, so I would find it hard to believe that there would be extra payments associated with it that weren't disclosed. I would be willing to bet that when the full agreement is disclosed three months from now you'll see that MNKD is providing Sanofi the rights to use the covered intellectual property as part of the already disclosed financial arrangement. As for inhaled Lantus, I don't remember hearing any speculation about that. Apparently the long acting nature of it is due to a pH change when it gets injected... "when a physiologic pH (approximately 7.4) is achieved the increase in pH causes the insulin to come out of solution resulting in the formation of higher order aggregates of insulin hexamers" These then take time to disassociate into usable insulin monomers. The lungs do provide the same non-acidic pH, but whether this prI had never heard it could be inhaled, either. The science is beyond me and I was just wondering. I guess my question is could it be used for long acting medicines? For example, I have heard the technosphere could be used for migraine meds for quicker action. That wouldn't be a quick in and out of body type medication. See where I am going?ocess would remain the same when Technospheres are inhaled is an interesting question. I had never heard it could be inhaled, either. The science is beyond me and I was just wondering. I guess my question is could it be used for long acting medicines? For example, I have heard the technosphere could be used for migraine meds for quicker action. That wouldn't be a quick in and out of body type medication. See where I am going? |
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Post by dreamboatcruise on Aug 14, 2014 20:45:15 GMT -5
Different things make different medications long acting. In some cases a drug simply has a very long half life and the effect of the drug is not dependent on precise blood concentrations, so high levels are achieved when it is first taken but the desired effect continues as the concentrations drop over time. In some cases the molecule with the desired activity is a metabolite of the drug... i.e. another chemical reaction in your body must transform the drug into the compound with the desired activity. In those cases it it might not matter how quickly the initial drug is absorbed, but rather how quickly this conversion then takes place in the body. Lantus isn't really metabolized, but rather a group of bound insulin comes apart over time making the usable sized insulin "monomers" available slowly. So I'm unsure about Lantus, but I'm sure there would be many drugs that are long acting that could be delivered by Technosphere.
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Post by Chris-C on Aug 14, 2014 22:53:35 GMT -5
Different things make different medications long acting. In some cases a drug simply has a very long half life and the effect of the drug is not dependent on precise blood concentrations, so high levels are achieved when it is first taken but the desired effect continues as the concentrations drop over time. In some cases the molecule with the desired activity is a metabolite of the drug... i.e. another chemical reaction in your body must transform the drug into the compound with the desired activity. In those cases it it might not matter how quickly the initial drug is absorbed, but rather how quickly this conversion then takes place in the body. Lantus isn't really metabolized, but rather a group of bound insulin comes apart over time making the usable sized insulin "monomers" available slowly. So I'm unsure about Lantus, but I'm sure there would be many drugs that are long acting that could be delivered by Technosphere. Nice thread. I've been wondering about the Technosphere process and how it might be licensed for use with different drugs. My wife is a biochemist, and she sometimes discusses how different solutions can be freeze dried yet retain their molecular properties. Not being a chemist, I have no idea how the process is done, and I suspect that it is highly proprietary. I'm guessing the particular genius of Technosphere is achieving a powder size that makes it easily inhaled and readily absorbed through the membrane walls of lung tissue. No doubt an excipient of some sort is used to stabilize the product before the lyophilization.The question is what is the process that enables the powder to be small enough to be inhaled? If any drug can be created in powder form, can any drug be used in the Technosophere process and thus have the potential for inhaled administration? If so, the Technosphere process could be quite significant as a revenue source if licensed. It might also be a means of extending expiring patents, which would make it very valuable indeed. I'm hoping the board has a biochemist or two with better knowledge of the process and technology than I, because it is possible that what Mr. Mann revealed on the call is precisely the right for SNY to use the process with one or more of their drugs in exchange, of course, for a portion of any revenue that results or even shared ownership of the new formulation. Comments from people who know what they are talking about would be most welcome  As always, GLTAL Chris-C |
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Post by liane on Aug 15, 2014 5:01:04 GMT -5
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Post by liane on Aug 15, 2014 5:23:05 GMT -5
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Post by Chris-C on Aug 15, 2014 10:24:01 GMT -5
Liane Thanks for posting these links on the process and patent. It appears to be quite innovative in that the process uses spray drying rather than freeze drying and MNKD had to perfect an entirely new way of creating the solution, carefully adding insulin to the DKP, and then spray drying it to achieve a concentrated powder with a particle size that flows readily when filled into a cartridge and dispensed through an inhaler device. This isn't your average pharmaceutical company, and it sounds like the process has enough flexibility to be applied to a number of agents other than insulin. Additional observations/comments welcome. Regards to all Chris-C |
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Post by mnholdem on Aug 15, 2014 13:41:04 GMT -5
Isn't it true that MNKD has the patent on the combination of Lantus with "A". So in theory, wouldn't the marketing of Lantus with "A" extend the patent of Lantus if used with "A"? If that is the case, wouldn't MNKD have a right to be compensated to a degree for Lantus after the patent runs out? And could Lantus be administered eventally by technosphere or would it cause it to be too fast acting? ... As for inhaled Lantus, I don't remember hearing any speculation about that. Apparently the long acting nature of it is due to a pH change when it gets injected... "when a physiologic pH (approximately 7.4) is achieved the increase in pH causes the insulin to come out of solution resulting in the formation of higher order aggregates of insulin hexamers" These then take time to disassociate into usable insulin monomers. The lungs do provide the same non-acidic pH, but whether this process would remain the same when Technospheres are inhaled is an interesting question. An excerpt from "The Fate of Mannkind" clarifies this (this article was written before the name was changed to Afrezza):There are two secrets to why Afresa behaves the way it does. The first is the insulin's delivery platform—the Technosphere particle. Described as "tiny sponges" by MannKind Chief Scientific Officer Peter Richardson, Technosphere particles are formed of multiple small crystals of fumaryl diketopiperazine (FDKP), which under certain conditions become just the right size for inhalation (approximately three to five microns in diameter). FDKP also has another property that makes it very useful for pulmonary drug delivery: Put it in an acid solution, and particles spontaneously assemble. Put the particles in a base environment—such as the human lung, with a pH of 7.3 or 7.4—and they dissolve. The particles have multiple surfaces; in photos, some Technosphere particles look a bit like a rose in bloom, flaring out in dozens of "petals." Powdered human recombinant insulin adheres to the particle's surfaces electrostatically, which means that the particle and drug do not interact chemically. Deep in the lung, the Technosphere dissolves and the insulin is absorbed in the bloodstream with remarkable speed. "Under the right conditions, FDKP forms a complex crystalline lattice which then forms the particles," says Richardson. "Someone thought: 'What happens if we put drugs or peptides on them?' They found that peptides do tremendously well in adhering to them. And because they're pH-sensitive, you have an opportunity for a direct delivery." At this point, secret number two kicks in. Conventional insulin tends to form hexamers—structures consisting of six monomers—the basic unit of insulin. Hexameric insulin cannot bind to insulin receptors, and has to be broken down before it's usable. Some insulin analogs, such as Lilly's Humalog and Novo Nordisk's Novolog, are modified to prevent the formation of hexamers. This makes them faster acting than traditional insulins, but because they are administered subcutaneously, they still take between 30 and 60 minutes to peak. The manufacturing process for Afresa results in monomeric insulin. Pulmonary delivery and instant availability makes Afresa faster than conventional fast-acting insulins. And that turns out to have many advantages for patients. In clinical trials, Afresa provides superior postprandial glycemic control, as well as improved fasting glucose control. It can easily be synchronized to meals, cutting chances of hypoglycemia and—very desirably—reducing the risk of weight gain. |
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Post by dreamboatcruise on Aug 15, 2014 19:45:08 GMT -5
... As for inhaled Lantus, I don't remember hearing any speculation about that. Apparently the long acting nature of it is due to a pH change when it gets injected... "when a physiologic pH (approximately 7.4) is achieved the increase in pH causes the insulin to come out of solution resulting in the formation of higher order aggregates of insulin hexamers" These then take time to disassociate into usable insulin monomers. The lungs do provide the same non-acidic pH, but whether this process would remain the same when Technospheres are inhaled is an interesting question. An excerpt from "The Fate of Mannkind" clarifies this (this article was written before the name was changed to Afrezza):... Though what I quoted above regarding pH and "higher order aggregates of insulin hexamers" is pertaining to Lantus not Afrezza. I believe this is something beyond just formation of the hexamers and may delay absorption of Lantus and subsequent disassociation into monomers beyond the normal time for hexamers to disassociate. Though I would not bet money on my limited understanding of this stuff. |
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