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Post by robbmo on Aug 11, 2023 14:41:56 GMT -5
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Post by phdedieu12 on Aug 12, 2023 5:53:52 GMT -5
Published April 2021
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Post by Clement on Aug 12, 2023 6:27:07 GMT -5
"Patent History Publication number: 20230248722 Type: Application Filed: Apr 30, 2021 Publication Date: Aug 10, 2023
Applicant: MANNKIND CORPORATION (WESTLAKE VILLAGE, CA) Inventors: Thomas Hofmann (Doylestown, PA), Stefan Ufer (Raleigh, NC), John J. Freeman, JR. (New Fairfield, CT) Application Number: 17/996,706" |
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Post by hellodolly on Aug 12, 2023 13:34:01 GMT -5
This just got very interesting. The patent has a list of embodiments wherein Clofazimine can be used to treat viral infections, including SARS-CoV=2. I'm not suggestung this is their intent but, it looks as if this drug has other uses that can later be explored:
"In embodiments disclosed herein there is provided a method for the treatment of viral infections comprising the use of clofazimine inhalation suspension (CIS) or inhalable dry powders as a countermeasure to coronaviruses and in particular, SARS-CoV-2, which causes COVID-19 disease. The clofazimine in the composition will inhibit viral infection and is administered directly to the lungs in a clofazimine suspension, or in dry powder form. CIS is currently in preclinical development for the treatment of both nontuberculous mycobacterial pulmonary disease, and tuberculosis and is currently undergoing first-in-human GLP toxicology studies.
In an exemplary embodiment, a method for treating viral infection comprising administering a composition comprising an antibiotic compound having the formula:
and a pharmaceutically acceptable carrier and/or excipient. In an embodiment, pharmaceutically acceptable derivatives, or salts of the compound are also used in the formulation alone or in combinations thereof with the compound, in particular, in compositions for pulmonary inhalation in the treatment of viral lung disease. In one embodiment, the compound is clofazimine, chlofazimine, N,5-bis(4-chlorophenyl)-3-propan-2-yliminophenazin-2-amine, clofazimine, clofaziminum, 3-(p-chloranilino)-10-(p-chlorphenyl)-2,10-dihydro-2-(isopropylimino)-phenazine, or polymorphic forms or polymorphs of clofazimine; including, a triclinic (F I) polymorph, a monoclinic (F II) polymorph, an orthorhombic crystal polymorph (F III) and a high temperature polymorph (F IV). Clofazimine salts include, for example, the hydrochloride salt of clofazimine, clofazimine acetate, clofazimine citrate, clofazimine formate, clofazimine phosphate, clofazimine oxalate, clofazimine sulfate and the like. In embodiments herewith, clofazimine may refer to any form of clofazimine when used alone, or in combination with others in a composition, unless derivatives, salts or polymorphs are specifically recited.
In another example embodiment, the composition comprising the antibiotic compound above is combined with a pharmaceutically acceptable carrier or excipient, including, a diketopiperazine to form a dry powder for oral inhalation, wherein the diketopiperazine is provided in the form of particles. In this embodiment, the diketopiperazine forms crystalline composite particles having a mass median diameter of <10 μm.
In an embodiment, a clofazimine compound in the compositions have antiviral activity against SARS-CoV-2 and have the potential to inhibit viral replication and eliminate viral disease, or eliminate symptoms of viral disease. In in vitro studies, clofazimine is able to reduce or eliminate viral replication by 40% at concentrations of 2.5 μM (or ˜1.2 μg clofazimine/ml). Clofazimine is used to treat bacterial infection and is provided as oral capsules in the treatment of, for example, leprosy and bacterial infections of the lungs, disclosed WO 2020/040818, which disclosure is incorporated by reference as it pertains.
In exemplary embodiments, clofazimine composition, including, CIS and dry powder formulations are used in the treatment of viral infections in general, and those affecting the lungs in particular. Those are infections by coronavirus, influenza, respiratory syncytial virus, Zika, Dengue and the like. In this embodiment, a composition for treating viral infections comprising clofazimine for the therapeutic treatment against SARS-CoV-2 is provided. The composition comprises clofazimine, a derivative of clofazimine, or a salt thereof, or combinations thereof, and a pharmaceutically acceptable carrier and/or excipient thereof for administering to a patient testing positive or diagnosed with the virus. In one embodiment herewith, the clofazimine composition is administered alone, or in combination with other antiviral therapy, including, ribavirin, acyclovir, remdesivir, interferon-beta 1b, lopinavir-ritonavir and the like. In these combination embodiments, the clofazimine composition is administered alone by inhalation and the secondary and/or tertiary therapy can be administered as an inhalable suspension, solution or a dry powder, or by other routes of administration such as oral tablets, oral capsules, injection, intravenously, and the like. In some embodiments, the CIS and dry powder compositions comprising clofazimine are administered in combination with other drugs, including, hydroxychloroquine and invermectin by their prescribed route of administration and dosages.
In some embodiments, clofazimine inhalable compositions, including CIS and dry powders can be used for the treatment of other diseases, including, of leprosy and other bacterial infections, including, in the treatment of nontuberculous mycobacterial diseases. In treatment of bacterial infection using clofazimine capsules, the drug is relatively well tolerated, with the main side effects including yellow skin discoloration and gastrointestinal issues at least in half the patients.
Clofazimine inhalation suspension for inhaled administration through a nebulized form optimizes clofazimine treatment in nontuberculous mycobacteria lung disease (NTM-PD) and tuberculosis (TB). By directly delivering the drug to the airways, CIS is expected to achieve therapeutic lung levels and reduce the incidence of the main side effects (listed above) without impacting therapeutic efficacy. Preclinical studies have evaluated CIS for the treatment of NTM-PD and TB, and a series of toxicology studies have been performed, which have shown that CIS is safe and well tolerated at doses up to ˜3.0 mg/kg (reaching lung levels of ˜10 μg clofazimine/g). The available pharmacokinetic (PK) and pharmacodynamics (PD) studies with a clofazimine inhalation suspension indicate that therapeutic lung concentrations for treatment of COVID-19 disease can be reached through an inhaled loading dose over one or two days and be maintained for up to two weeks.
The benefits and advantages of inhaled clofazimine compositions are numerous and, include, targeted lung dosing (with a fraction of the oral dose), to avoid side effects of high systemic clofazimine levels; protection/prevention of lung infection with virus on lung surface and respiratory cell lining; ability to deliver inhaled therapy at home and away from infectious hospital setting; topical “lung loading” over few days/doses, and prolonged activity with long half-life of clofazimine in the lung.
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Post by uvula on Aug 12, 2023 15:16:54 GMT -5
This is the application. Was the patent recently granted?
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Post by prcgorman2 on Aug 12, 2023 17:19:58 GMT -5
Yes, last week. Look up above.
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Post by MnkdWASmyRtrmntPlan on Aug 12, 2023 17:50:16 GMT -5
Hello, Hello D. Wow, did you write that post?  That's a little over my head. I counted 15 occurances of the word embodiment. I had to look it up to see if there was some definition that I didn't know. Well, there isn't really, but still, that's a complicated post. Here's one that's a whole lot lighter and easier to understand - www.npr.org/2023/08/06/1192388382/whats-behind-the-increase-in-leprosy-cases-in-floridaI heard this podcast last week and it is a currently on-topic and relevant for Clofazimine, and very easily digestible. It's a 2 to 5 minute read, or 6 minute listen. For me, listening to NPR podcasts are much easier and relaxing than reading. I like to sit down, close my eyes, relax with a cup of coffee and listen in the morning when I'm waking up. There's both an NPR and an NPR-One app that both have the same daily news articles, but just different app designs. I actually have both installed on my phone and really enjoy them. It's kinda addicting, though. |
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Post by uvula on Aug 12, 2023 18:13:08 GMT -5
Yes, last week. Look up above. The title of this thread says the patent was issued. The link in the first post is for the patent application. Not sure why the thread starter didn't post a link showing that the patent was granted if it was actually granted. Publication date for the application does not mean it was granted. |
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Post by prcgorman2 on Aug 12, 2023 20:22:00 GMT -5
Yes, last week. Look up above. The title of this thread says the patent was issued. The link in the first post is for the patent application. Not sure why the thread starter didn't post a link showing that the patent was granted if it was actually granted. Publication date for the application does not mean it was granted. Yup, I spoke (wrote) too soon. Took a little bit of more research and I still don't understand the full details, but basically you're correct. From what I found (and now cannot re-find) it looks like there was a provisional patent (basically an inexpensive patent placeholder for up to 1 year that doesn't even get inspected) and then a patent application. There is apparently an 18-month window after which a patent application is published. I don't see that there is yet a patent based on the application. This is not surprising as the patent process can commonly can take 3 to 5 years between application and grant of a patent. There appear to be filings for international patents as well. I didn't try to research anything of those.
Basically, the situation is, "patent pending".
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Post by hellodolly on Aug 13, 2023 10:19:47 GMT -5
Hello, Hello D. Wow, did you write that post? That's a little over my head. I counted 15 occurances of the word embodiment. I had to look it up to see if there was some definition that I didn't know. Well, there isn't really, but still, that's a complicated post. Here's one that's a whole lot lighter and easier to understand - www.npr.org/2023/08/06/1192388382/whats-behind-the-increase-in-leprosy-cases-in-floridaI heard this podcast last week and it is a currently on-topic and relevant for Clofazimine, and very easily digestible. It's a 2 to 5 minute read, or 6 minute listen. For me, listening to NPR podcasts are much easier and relaxing than reading. I like to sit down, close my eyes, relax with a cup of coffee and listen in the morning when I'm waking up. There's both an NPR and an NPR-One app that both have the same daily news articles, but just different app designs. I actually have both installed on my phone and really enjoy them. It's kinda addicting, though. I copied that from the application that was just published. My take on "embodiment" is the use cases represents prior trials/approvals for the indications noted, i.e.' SARS-CoV-2, NTMN, Dengue Fever, etc. using clofazimine. Essentially, they are saying that the drug is already being used in a wide array of other diseases, likely to bypass more regulatory hoops as in when patents are being applied brand new molecules. As I believe, MNKD is likely still only going after NTM but, it's interesting that the same drug is used for other viral infections that impact the lungs and respiratory system. |
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Post by agedhippie on Aug 13, 2023 13:02:36 GMT -5
... Essentially, they are saying that the drug is already being used in a wide array of other diseases, likely to bypass more regulatory hoops as in when patents are being applied brand new molecules. As I believe, MNKD is likely still only going after NTM but, it's interesting that the same drug is used for other viral infections that impact the lungs and respiratory system. The patent process in these sorts of patents isn't about winning, it's about slowing down a competitor (eg. UTHR vs. LQDA) by getting your patent into the Orange book and forcing the new entrant to get your patent revoked. With that in mind you claim for absolutely everything because the aim isn't to win but rather to delay. In this case since the Chinese have already put and antibiotic on FDKP there is a lot of scope for prior art challenges. This is what I dislike about the patent system and companies who use patents like that. It creates a slanted playing field and favors larger companies (again UTHR vs. LQDA) although I entirely understand why companies do it. This also why I don't take big pharma conspiracies against Mannkind seriously, they would have simply gone for Mannkind in court using their patents whereas messing with the stock market is illegal and an unnecessary risk. |
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Post by MnkdWASmyRtrmntPlan on Aug 14, 2023 15:10:45 GMT -5
I copied that from the application that was just published. My take on "embodiment" is the use cases represents prior trials/approvals for the indications noted, i.e.' SARS-CoV-2, NTMN, Dengue Fever, etc. using clofazimine. Essentially, they are saying that the drug is already being used in a wide array of other diseases, likely to bypass more regulatory hoops as in when patents are being applied brand new molecules. As I believe, MNKD is likely still only going after NTM but, it's interesting that the same drug is used for other viral infections that impact the lungs and respiratory system. Thanks for your explanation, HD. That all makes sense. |
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That's a little over my head. I counted 15 occurances of the word embodiment. I had to look it up to see if there was some definition that I didn't know. Well, there isn't really, but still, that's a complicated post.