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Post by peppy on Nov 27, 2023 15:41:59 GMT -5
Peppy . I thought Afrezza avoided first pass hepatic metabolism to its advantage 🤔? "These include loss of early insulin response, hepatic and peripheral (muscle and fat) insulin resistance, excessive glucagon secretion, and accelerated gastric emptying. All of these dysfunctions lead to abnormalities in glucose and lipid homeostasis Loss of the early insulin response is a defect found in patients with type 1 and type 2 diabetes Loss of the early insulin response is a defect found in patients with type 1 and type 2 diabetesInsulin Response to Glucose Challenge The insulin response to a continuous infusion of intravenous glucose has 2 distinct phases (Figure 9). Insulin levels rise sharply within 3 to 5 minutes, peak in approximately 10 minutes, and then decline; this is known as the first-phase insulin response. This is followed by a more gradual and progressive increase in insulin levels that lasts as long as glucose is infused (i.e., the second-phase insulin response).51 The normal early insulin response rapidly suppresses, or “switches off,” hepatic glucose output, which prevents excessive postprandial glucose excursions" web.archive.org/web/20160325133540/http://www.mannkindcorp.com/Collateral/Documents/English-US/Postprandial%20Hyperglycemia.pdflook at figure 9 on page 8. My quickly easy version. Afrezza insulin, alveoli, pulmonary capillaries, through the pulmonary vein, the left atrium and ventricle to the liver; through the blood stream and the signal to stop the gluconeogenesis and the post meal glucose does not shoot up as high.  . ==================================================== |
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Post by mango on Nov 27, 2023 16:15:58 GMT -5
Aged is an expert on diabetes and treatment options. The Omnipod 5. www.omnipod.com/what-is-omnipod/omnipod-5Aged pointed out to me years ago, it is a miniature auto syringe that can be digitally programed. Computerized now with a Continuous glucose monitor as the feed back system. mpg54 , the real upside in Afrezza is the delivery system, into the left atrium, left ventricle and systemic blood stream allows for 35 min peak time and 90 min out of the system for a 4 unit cartridge. *if blood glucose level is over 100 at 60 mins a second dose of afrezza may be necessary. the omnipod because the delivery is subcutaneous, Peak is two hours and it takes 5 hours to get out of the system as the delivery is through the capillaries to the blood stream a slow go. . One more thing about Afrezza. Afrezza dosing allows for, "permits insulin to find its way into the portal circulation readily and to undergo the first-pass metabolism in the liver subsequently." stevil , when he was still in medical school was the first to tell me about first pass. First pass stops the liver from releasing glucose. 1. subcutaneous insulin does not have a first pass. 2. first pass is probably the reason Afrezza is able to keep the initial blood glucose levels in check with meals, or said differently, why the post meal blood glucose levels are lower with afrezza than subq. . Afrezza avoids the hepatic first pass metabolism. Well, anything delivered via Technosphere inhalers does as it mimics intra-arterial administration. However, it’s believed that it is not necessarily the avoidance of the first-pass that makes Afrezza so effective, but rather the extremely rapid absorption. Oral meds undergo the hepatic first-pass metabolism. Which is why the oral insulin could never compete with Afrezza. |
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Post by peppy on Nov 27, 2023 16:27:03 GMT -5
Mango,
there is 1st phase
there is also first pass.
Can you expound on the difference?
please.
Was using them interchangeably? yikes.
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Post by lennymnkd on Nov 27, 2023 17:25:02 GMT -5
And Al would discuss less API FOR THAT REASON.
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Post by mango on Nov 27, 2023 18:15:45 GMT -5
Mango, there is 1st phase there is also first pass. Can you expound on the difference? please. Was using them interchangeably? yikes. First phase insulin secretion is an imprecise, rapid burst of insulin in response to a rise in blood glucose from a meal. Beta cell memory. We already know diabetes is just the dysregulation of blood glucose. Nothing more, nothing less. Afrezza fixes the underlying issue of the loss of first phase insulin response, which is directly responsible for the dysregulation of blood glucose, which causes diabetes. Afrezza fixes that. |
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Post by prcgorman2 on Nov 28, 2023 8:49:55 GMT -5
Mango, there is 1st phase there is also first pass. Can you expound on the difference? please. Was using them interchangeably? yikes. First phase insulin secretion is an imprecise, rapid burst of insulin in response to a rise in blood glucose from a meal. Beta cell memory. We already know diabetes is just the dysregulation of blood glucose. Nothing more, nothing less. Afrezza fixes the underlying issue of the loss of first phase insulin response, which is directly responsible for the dysregulation of blood glucose, which causes diabetes. Afrezza fixes that. I’ll argue that Afrezza resembles the “first phase insulin secretion” and in so doing signals the liver to reduce (or stop?) creating glucose from fat. Am I wrong? |
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Post by agedhippie on Nov 28, 2023 9:07:26 GMT -5
I’ll argue that Afrezza resembles the “first phase insulin secretion” and in so doing signals the liver to reduce (or stop?) creating glucose from fat. Am I wrong? You are correct, except that the liver has it's own store of glucose which it maintains and draws on rather than creating it from fat. You see this reserve talked about most often in the context of a glucose dump when your liver responds to glucagon or adrenaline. |
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Post by cppoly on Nov 29, 2023 17:30:43 GMT -5
Aged, I'm having trouble with the December 4th oral argument UTHR vs LQDA link you sent a while ago. When I go to it, it's just a blank page sort of
Can you post the specific link to listen to the argument?
Do you know what time it will be?
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Post by agedhippie on Nov 29, 2023 17:52:48 GMT -5
Aged, I'm having trouble with the December 4th oral argument UTHR vs LQDA link you sent a while ago. When I go to it, it's just a blank page sort of Can you post the specific link to listen to the argument? Do you know what time it will be? I am not sure which link that was, but I think this is what you are after - cafc.uscourts.gov/home/oral-argument/listen-to-oral-arguments/They stream it live and post a recording at the end of the day as well. There is an archive of past recordings you can search as well. |
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Post by longliner on Dec 1, 2023 15:45:08 GMT -5
On November 30, 2023, United Therapeutics filed an amended complaint in the District Court adding allegations that the Company infringes the ’327 Patent as a result of its amendment to add the PH-ILD indication to the label for YUTREPIA.
on June 29, 2023, United Therapeutics Corporation (“United Therapeutics”) received a notice of allowance with respect to its patent application number 17/233,061, the claims of which generally cover the treatment of patients having pulmonary hypertension associated with interstitial lung disease (“PH-ILD”) through the inhaled administration of treprostinil. On November 28, 2023, a new patent, U.S. Patent No. 11,826,327 (the “’327 Patent”) was issued from that patent application.
From form 8-k
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Post by peppy on Dec 1, 2023 15:49:18 GMT -5
On November 30, 2023, United Therapeutics filed an amended complaint in the District Court adding allegations that the Company infringes the ’327 Patent as a result of its amendment to add the PH-ILD indication to the label for YUTREPIA. From form 8-k oh, UTHR popped yesterday. |
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Post by agedhippie on Dec 1, 2023 16:13:36 GMT -5
On November 30, 2023, United Therapeutics filed an amended complaint in the District Court adding allegations that the Company infringes the ’327 Patent as a result of its amendment to add the PH-ILD indication to the label for YUTREPIA. on June 29, 2023, United Therapeutics Corporation (“United Therapeutics”) received a notice of allowance with respect to its patent application number 17/233,061, the claims of which generally cover the treatment of patients having pulmonary hypertension associated with interstitial lung disease (“PH-ILD”) through the inhaled administration of treprostinil. On November 28, 2023, a new patent, U.S. Patent No. 11,826,327 (the “’327 Patent”) was issued from that patent application. From form 8-k The LQDA response: www.streetinsider.com/SEC+Filings/Form+8-K+Liquidia+Corp+For%3A+Nov+30/22479032.htmlThis is the relevant bit: Because neither the ’793 Patent nor the ’327 Patent was issued prior to the filing of the original NDA for YUTREPIA, we believe United Therapeutics is not entitled to a statutory 30-month stay with respect to either of these patents.UTHR have the same problem as with their standalone lawsuit for '327, it wasn't in the Orange book when LQDA made their filing for PH-ILD. That means it isn't covered by the Hatch Waxman Act since that requires the patent to be in the Orange book when the filing is made (the Act set up the Orange book specifically to clarify what was and wasn't covered.) On the face of it I don't think UTHR has a case, but then I am not a lawyer and I long ago gave up being surprised by what the courts will do. |
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Post by longliner on Dec 1, 2023 17:41:04 GMT -5
Since the expiration of protection for ILD has not expired (march 31, 2024). Uthr is well within their rights to seek injunction. U.S. Code § 156 - Extension of patent term I have to add that the original NDA for Yutrepia was for PH class 1 and did not include PH-ILD. LQDA subsequently submitted a supplemental NDA to include PH-ILD which is in review with the FDA currently and has not been issued. UTHR actually had no standing until the supplemental NDA was filled and the patent was approved. Looks like it can drag out for 30 months but it may all be mute if UTHR is successful on the case on Monday. Enjoy the weekend! (All the above is thanks to Itza) I will add that some time ago Martine stated that she didn't believe Yutrepia would reach the market before 2027 (if ever). I would love to know what went into her calculation. Who knows? In addition to a 30 month stay, maybe a citizen's petition is in Liquidia's future.  |
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Post by robbmo on Dec 1, 2023 19:04:50 GMT -5
On November 30, 2023, United Therapeutics filed an amended complaint in the District Court adding allegations that the Company infringes the ’327 Patent as a result of its amendment to add the PH-ILD indication to the label for YUTREPIA. on June 29, 2023, United Therapeutics Corporation (“United Therapeutics”) received a notice of allowance with respect to its patent application number 17/233,061, the claims of which generally cover the treatment of patients having pulmonary hypertension associated with interstitial lung disease (“PH-ILD”) through the inhaled administration of treprostinil. On November 28, 2023, a new patent, U.S. Patent No. 11,826,327 (the “’327 Patent”) was issued from that patent application. From form 8-k The LQDA response: www.streetinsider.com/SEC+Filings/Form+8-K+Liquidia+Corp+For%3A+Nov+30/22479032.htmlThis is the relevant bit: Because neither the ’793 Patent nor the ’327 Patent was issued prior to the filing of the original NDA for YUTREPIA, we believe United Therapeutics is not entitled to a statutory 30-month stay with respect to either of these patents.UTHR have the same problem as with their standalone lawsuit for '327, it wasn't in the Orange book when LQDA made their filing for PH-ILD. That means it isn't covered by the Hatch Waxman Act since that requires the patent to be in the Orange book when the filing is made (the Act set up the Orange book specifically to clarify what was and wasn't covered.) On the face of it I don't think UTHR has a case, but then I am not a lawyer and I long ago gave up being surprised by what the courts will do. I think the grey area here is, LQDA had been notified that the patent claims for '327 had been approved for the patent grant, and they stated they were evaluating the claims before they filed for PH-ILD. In reading the orange book guidelines, LQDA will have to amend its application to include a patent certification statement addressing the '327 patent, though I do not know what that means as far as a 30 month stay goes. I agree that the rules state UTHR is not entitled to a mandatory 30 month stay at that point. However, I believe UTHR could make a good argument based on the intent of the law, versus the technicality of the wording. LQDA knew about the patent approval and claims well before they filed for PH-ILD, and the law is intended to protect patent holders from infringement on known, valid, patents. |
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Post by agedhippie on Dec 1, 2023 19:30:00 GMT -5
Since the expiration of protection for ILD has not expired (march 31, 2024). Uthr is well within their rights to seek injunction. U.S. Code § 156 - Extension of patent term I have to add that the original NDA for Yutrepia was for PH class 1 and did not include PH-ILD. LQDA subsequently submitted a supplemental NDA to include PH-ILD which is in review with the FDA currently and has not been issued. UTHR actually had no standing until the supplemental NDA was filled and the patent was approved. Looks like it can drag out for 30 months but it may all be mute if UTHR is successful on the case on Monday. Enjoy the weekend! (All the above is thanks to Itza) I will add that some time ago Martine stated that she didn't believe Yutrepia would reach the market before 2027 (if ever). I would love to know what went into her calculation. Who knows? In addition to a 30 month stay, maybe a citizen's petition is in Liquidia's future. The FDA will not approve Yutrepia for PH-ILD until the exclusivity expires in March so a lawsuit is unnecessary. I am fairly certain this is just about spreading FUD and I confidently await the citizen's petition, or a lawsuit for animal cruelty - whichever comes first  The important thing as I understand it was that the NDA was filed before the patent was in the Orange book, it doesn't need to be approved but LQDA needs to be able to say that at the time of filing there was no patent in the Orange book which they did. The stay is issued only if the patent is filed before the NDA. |
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