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Post by agedhippie on Jul 7, 2023 9:21:33 GMT -5
Mnkd cannot manufacture clofazimine. Mnkd cannot produce clofazimine. Doesn't matter what word(s) you want to use. Not a complaint. Just a fact that some people here were aparently not aware of. Point remains, it will be produced like Afrezza and Tyvaso in Danbury instead of Germany, and I see that as a good thing I think you are missing the point. Mannkind could package the API (Clofazimine), but they could not manufacture the API even if they wanted to. There is dependency on a 3rd party to supply the API unless Mannkind wants to branch out into manufacturing the API as well which would be beyond stupid (it's a very cheap drug with lousy margins and would take forever to recoup the plant build out costs.) As hellodolly pointed out to me this is delivered via a nebulizer - Mannkind would need to build manufacturing for a tactical objective when their strategic direction is Technosphere. Far better to work on the feasibility of migrating it to Technosphere as described in the 10K. That will take time though and you could probably use the development of Tyvaso DPI, another nebulizer to TS migration as a guideline for the timescales involved. At the point the TS migration happens (if it happens) then the nebulizer manufacturing plant becomes redundant. In short; moving manufacturing to Danbury before the transition to TS would be a bad thing.
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Post by agedhippie on Jul 6, 2023 19:57:38 GMT -5
Prior art. It makes a patent defense borderline impossible. I’m not a patent attorney (or any kind of attorney) but my understanding is prior art is what can prevent filing a patent application (because the patent will most likely be denied). I assume a previously unspecified formulation of GLP-1 in inhalable form could be patentable. As you’ve pointed out, however, patent attorneys like to be very broad in their claims so being very specific might result in a patentable filing but not be of much offensive or defensive value. All that said, I doubt IPR or lack thereof is the major inhibiting factor. My guess is time, cost, and labor prevent it from being a priority. I'm not a patent attorney either but I have been on the patentee side a few times You would need something that was fundamentally different from the old patent since that would now be the prior art. The issue the patent had, and why it was abandoned from what I can make out, was because of prior art - there was already something so close that the patent office challenged it (the office action) and Mannkind decide it was better just dump it.
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Post by agedhippie on Jul 6, 2023 17:22:36 GMT -5
Aged - since you have been through the patent process many times can you please explain why Peter would assign this patent? In 2015 Peter was working for Alcon. In 2008 or there abouts MNKD stopped work on TS GLP1. He left MNKD in 2012. The publication date is 3/19/2015, nearly three years later. IDK, maybe its me but if worked on something 7 years ago and nothing was done with it and I still thought it was a great idea I am not sure I would go back to my previous employer who had no interest. Then Mago posts in 12/2022 MNKD files a very similar patent. Lets assume the publication date is 18 months after the PTO received it. It almost seems like Peter started putting the application together right after he left MNKD. Does that seem correct? He will assign the patent because that's what his contract of employment says he will do. It's a pretty standard clause if you work in an area where discovering new things or processes is a possibility. By all means cut out your old employer, but don't be surprised when you end up in court and they win, it's a simple breach of contract. I don't think you understand the patent process so lets take this one as an example. Richardson will not have filed this, he is just one of four inventors on that filing, it will have been done by Mannkind during an intellectual property sweep. These are periodic sweeps through the company's assets looking for patentable material. Everything then gets thrown at the patent attorney who decides if it's patentable in their view - this is an extremely low bar for reasons that become clear. The date the work is done is irrelevant to the filing which is often, as in this case, years later. There is a common misconception that patents are there to stop people from stealing your invention. These days patents are primarily used as weapons in court, both offensively and defensively. Defensively they are used to counter-sue for breaching one of your patents if someone tries to sue you. Offensively you get patent trolls and companies like UTHR using them offensively.
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Post by agedhippie on Jul 6, 2023 16:10:14 GMT -5
Abandoned or not, nothing to stop another investigation and more patent filings. Prior art. It makes a patent defense borderline impossible.
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Post by agedhippie on Jul 6, 2023 16:01:29 GMT -5
Conversion into clofazimine DPI is already done at Danbury. I don't think the API supplier can be swapped, but not cut out. Clofazimine is a very cheap API, and MNKD isn't looking for large volumes so there is no way this gets bought in-house (timelines, costs, licensing, ROI, staffing all block this.) The far simpler solution is to second source the API from another manufacturer as well. Always wondered about this being converted to DPI when this will be used with a nebulizer in PHII/III not their inhaler. It's not diabetes so I don't pay as much attention as I should. This will be delivered via a nebulizer? What happened to TS?
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Post by agedhippie on Jul 6, 2023 6:06:05 GMT -5
Publication date: 2015-03-19 When did Peter Richardson leave MNKD? Does Peter hold this patent outside of MNKD? This patent mentions obesity 21 times. It seems Peter and team thought it "would" help with obesity rather than "may". It seems like they were going down the path of taking a puff before a meal or snack. "The method of treating hyperglycemia, diabetes, and/or obesity can be designed so that the patient can receive at least one dose of a GLP-1 formulation in proximity to a meal or snack" Read more: www.patentsencyclopedia.com/app/20150080298Of course the patent mentions obesity. The patent attorney would be negligent if it didn't. The way patents work is that you have at least one solid thing to hang the patent on, in this case it's controlling glucose (134 mentions), and then you tack on every vaguely possible situation and permutation because it's free so why not. I have patents in my name that the attorneys added things they thought were possible applications added even though I disagreed - needless to say their version won! It's extremely unlikely that Richardson has not assigned this patent to Mannkind. Certainly all my patents are assigned and most contracts specify that they own any patents produced.
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Post by agedhippie on Jul 6, 2023 5:50:35 GMT -5
Sounds like bad news, good news. Now we can bring the production to Danbury and control the process, and cut out the supplier.... Conversion into clofazimine DPI is already done at Danbury. I don't think the API supplier can be swapped, but not cut out. Clofazimine is a very cheap API, and MNKD isn't looking for large volumes so there is no way this gets bought in-house (timelines, costs, licensing, ROI, staffing all block this.) The far simpler solution is to second source the API from another manufacturer as well.
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Post by agedhippie on Jul 4, 2023 14:26:36 GMT -5
...because with one significant market event all the best-laid plans will go to hell in a hand basket. Many is the time I have escorted that hand basket.... " Markets can remain irrational a lot longer than you and I can remain solvent"
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Post by agedhippie on Jul 4, 2023 14:19:17 GMT -5
Sorry, yes you are right. The delay is to a phase 2/3 trial, not a phase 1 trial. The share price impact stands though as I don't see that getting factored in until after the trial results (usually the phase 2, but in this case if there is a single trial then after that)
Clofazimine is used in this role outside the US so I expect it to work. The question will be efficiency and side effects when delivered via DPI.
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Post by agedhippie on Jul 4, 2023 13:40:03 GMT -5
Found it:Direct delivery of clofazimine to the lungs may provide a treatment option for nontuberculous mycobacterial (NTM) lung disease that potentially overcomes systemic toxicity and lessens side effects. ... Aged - there is that pesky word again "may" which Peter used with TS GLP1 - "Direct delivery of clofazimine to the lungs may provide" In both cases for the same reason - no phase 2 trial data to quantify the impact and dosing. The difference is that clofazimine is currently used outside the US to treat nontuberculous mycobacterial (NTM) lung disease, whereas GLP-1 isn't used at all. The "may" in the case of inhaled clofazimine is because they are speculating that it will avoid the rather nasty side effects of the drug, whereas the "may" in the GLP-1 comment was because they have no idea if it is viable because of the fast clearance (the block to the use of GLP-1 before analogs), never mind if there are side effects. From a share price POV I don't see the delay having a material effect on the share price because it's only a phase 1 trial and generally those are seen as speculative (basically try-outs) so they don't get factored into the share price. That comes after the phase 2 results.
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Post by agedhippie on Jul 2, 2023 9:18:33 GMT -5
The problem remains; that test was done with GLP-1 and not GLP-1 analogs which is needed to overcome the clearance rate of GLP-1. Suppose you take a puff of GLP-1 before you eat that ice cream, what do you do three minutes later when the GLP-1 has worn off and you start to feel you can eat again? Do you take another puff, and then what do you do three minutes later when that has worn off? This is exactly why GLP-1 analogs were designed, you need an extended half-life to avoid having to continuously dose. Based on Peter Richardson's comments I don't think he agrees with you based on what he was seeing. ... Reread what he said. Richardson says absolutely nothing about how to overcome the rapid clearance. His speculation is purely whether it could work, "In addition, if we are able to demonstrate the same weight reduction or satiety effects seen with long-acting analogues of native GLP, MKC253 may have therapeutic potential in obesity." How to achieve those effects is not touched on at all so it's hard to say he disagrees with me.
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Post by agedhippie on Jul 1, 2023 8:15:34 GMT -5
As an aside the 1mg Ozempic pen's list price is $573 in the US, and the UK NHS pays $24 per pen (they are free to diabetics)
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Post by agedhippie on Jul 1, 2023 5:15:49 GMT -5
... If TS GLP1 worked how much could be sold annually, assuming its a $50B market. If Peter was right and you don't get the nausea with TS this seems like a potential blockbuster to me even if you need a puff before each meal/snack/cup of ice cream. The problem remains; that test was done with GLP-1 and not GLP-1 analogs which is needed to overcome the clearance rate of GLP-1. Suppose you take a puff of GLP-1 before you eat that ice cream, what do you do three minutes later when the GLP-1 has worn off and you start to feel you can eat again? Do you take another puff, and then what do you do three minutes later when that has worn off? This is exactly why GLP-1 analogs were designed, you need an extended half-life to avoid having to continuously dose.
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Post by agedhippie on Jul 1, 2023 5:08:08 GMT -5
Agree, but most people are able to maintain a weight and not just bounce back and forth in a wide range. The hope would be that they could lose the weight to get to a healthier weight, and then maintain at that healthier weight. I largely agree with most of your other observations too. The people who are taking GLP-1 for weight loss in almost all cases regain weight when they stop. There is a long debate as to how this gets funded because there isn't a lot of point in reducing peoples weight for a couple of years, taking them off GLP-1 and having them promptly regain the weight. The likelihood is that GLP-1 treatment has to be indefinite, in which case how can this be afforded given the number of patients and the cost of the drugs.
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Post by agedhippie on Jun 26, 2023 10:12:02 GMT -5
Aged - these T1s have been so out of control for so long it would be some what dangerous to get them under 140 in a study like this. However, if you are following some of the social media a lot of them are now targeting 100 as their baseline and are seeing no hypo concerns. ... I have no idea where you get this stuff from, but it's flatly wrong. For a start the 770G pumps that they were using are hardwired to target 120, and the Tandem IQ pumps usually target 100. There has been a PPG target for years, it's to be below 180 two hours after the meal. That aligns nicely with TIR. If Irl Hirsch is going to argue with it should be lower then he is going to have to argue that the TIR limit should be lower. There has been no evidence to date that he is going to do that, but if you know of any I would be interested.
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