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Post by anderson on Jul 25, 2023 9:10:39 GMT -5
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Post by peppy on Jul 25, 2023 9:17:40 GMT -5
Imatinib is a type of cancer growth blocker called a tyrosine kinase inhibitor (TKI). Tyrosine kinases are proteins that cells use to signal to each other to grow. They act as chemical messengers. There are a number of different tyrosine kinases and blocking them stops the cancer cells growing. Imatinib (Glivec) | Cancer information - Cancer Research UK www.cancerresearchuk.org/about-cancer/treatment/drugs/imatinib#:~:text=Imatinib%20is%20a%20type%20of,stops%20the%20cancer%20cells%20growing. www.accessdata.fda.gov/drugsatfda_docs/label/2008/021588s024lbl.pdf-------------------------INDICATIONS AND USAGE------------------------------ Gleevec is a kinase inhibitor indicated for the treatment of: • Newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Follow-up is limited to 5 years (1.1) • Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy (1.2) • Pediatric patients with Ph+ CML in chronic phase who are newly diagnosed or whose disease has recurred after stem cell transplant or who are resistant to interferon-alpha therapy. There are no controlled trials in pediatric patients demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival (1.3) • Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (1.4) • Adult patients with myelodysplastic/ myeloproliferative diseases (MDS/MPD) associated with PDGFR (platelet-derived growth factor receptor) gene re-arrangements (1.5) • Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c- Kit mutational status unknown (1.6) • Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown (1.7) • Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) (1.8) • Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). (1.9) |
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Post by peppy on Jul 25, 2023 9:35:52 GMT -5
mango stevilCompositions and Methods of Making the Same In another aspect a dry powder inhalable composition is provided, the composition comprising imatinib, a pharmaceutically acceptable salt, or a derivative thereof, and optionally one or more excipients. Regarding the composition in its solid dry form, the excipient also forms the solid matrix in which the imatinib, a salt, or derivative thereof is dispersed. In a preferred embodiment, the main excipient is (E)-3,6-bis[4-(N-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine, fumaryl diketopiperazine (FDKP), or a salt thereof. The excipient may be processed to obtain crystals of an appropriate size to form crystalline powders, crystalline composite powders, or dissolved to obtain amorphous powders. The composition may include excipients such as lactose, corn starch, or the like, glidants such as magnesium stearate, etc., emulsifying agents, suspending agents, stabilizers, and isotonic agents, etc. If desired, a sweetening agent and/or a flavoring agent may be added. Exemplary excipients include, without limitation, polyethylene glycol (PEG), hydrogenated castor oil (HCO), cremophors, carbohydrates, starches (e.g., corn starch), inorganic salts, antimicrobial agents, antioxidants, binders/fillers, surfactants, lubricants (e.g., calcium or magnesium stearate), glidants such as talc, disintegrants, diluents, buffers, acids, bases, film coats, combinations thereof, and the like. Other examples of soluble excipients that may be used in the composition are alitame, acesulfame potassium, aspartame, saccharin, sodium saccharin, sodium cyclamate, sucralose, threalose, xylitol, citric acid, tartaric acid, cyclodextrins, dextrins, hydroxyethylcellulose, gelatine, malic acid, maltitol, maltodextrin, maltose, polydextrose, tartaric acid, sodium or potassium bicarbonate, sodium or potassium chloride, sodium or potassium citrate, phospholipids, lactose, sucrose, glucose, fructose, mannitol, sorbitol, natural aminoacids, alanine, glycine, serine, cysteine, phenylalanine, tyrosine, tryptophan, histidine, methionine, threonine, valine, isoleucine, leucine, arginine, lysine, aspartic acid, glutamic acid, asparagine, glutamine, proline, their salts, and their possible simple chemical modifications such as in N-acetylcysteine, and carbocysteine. The preferred soluble excipients are alkaline metals salts such as sodium chloride or potassium chloride, and sugars, such as lactose. Specific carbohydrate excipients include, for example, monosaccharides, such as fructose, maltose, galactose, glucose, D-mannose, sorbose, and the like; disaccharides, such as lactose, sucrose, trehalose, cellobiose, and the like; polysaccharides, such as raffinose, melezitose, maltodextrins, dextrans, starches, and the like; and alditols, such as mannitol, xylitol, maltitol, lactitol, xylitol, sorbitol (glucitol), pyranosyl sorbitol, myoinositol, and the like. In some embodiments, the excipient comprises a surfactant. The surfactant of the composition can be chosen among different classes of surfactants of pharmaceutical use.
Surfactants suitable to be used are all those substances characterized by medium or low molecular weight that contain a hydrophobic moiety, generally readily soluble in an organic solvent but weakly soluble or insoluble in water, and a hydrophilic (or polar) moiety, weakly soluble or insoluble in an organic solvent but readily soluble in water. Surfactants are classified according to their polar moiety. Therefore surfactant with a negatively charged polar moiety are called anionic surfactants, while cationic surfactants have a positively charged polar moiety. Uncharged surfactant are generally called non-ionic, while surfactant charged both positively and negatively are called zwitterionic. Examples of anionic surfactants are salts of fatty acids (better known as soaps), sulfates, sulfate ethers and phosphate esters. Cationic surfactants are frequently based on polar groups containing amino groups. Most common non-ionic surfactants are based on polar groups containing oligo-(ethylene-oxide) groups. Zwitterionic surfactants are generally characterized by a polar group formed by a quaternary amine and a sulfuric or carboxylic group. Specific examples of this application are the following surfactants: benzalkonium chloride, cetrimide, docusate sodium, glyceryl monolaurate, sorbitan esters, sodium lauryl sulfate, polysorbates, phospholipids, biliary salts. Non-ionic surfactants, such as polysorbates and polyethylene and polyoxypropylene block copolymers, known as “Poloxamers,” may be used. Polysorbates are described in the CTFA International Cosmetic Ingredient Dictionary as mixtures of sorbitol and sorbitol anhydride fatty acid esters condensed with ethylene oxide. Particularly preferred are non-ionic surfactants of the series known as “Tween,” in particular the surfactant known as “Tween 80,” a polyoxyethylensorbitan. Additional exemplary excipients include surfactants such as other polysorbates, e.g., “Tween 20” and pluronics such as F68 and F88 (both of which are available from BASF, Mount Olive, N.J.), sorbitan esters, lipids (e.g., phospholipids such as lecithin and other phosphatidylcholines, and phosphatidylethanolamines), fatty acids and fatty esters, steroids such as cholesterol, and chelating agents, such as EDTA, zinc and other such suitable cations. The presence of a surfactant, and preferably of Tween 80, may be necessary to reduce electrostatic charges found in compositions without it, the flow of the powder and the maintenance of the solid state in a homogeneous way without initial crystallization. Phospholipids may be included in the above mentioned definition of surfactants or excipients.
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Post by hellodolly on Jul 25, 2023 9:58:25 GMT -5
Is imatinib the second molecule? That's my question, too. I'm looking for dates in the materials posted so far. If this was the case, will MNKD or UTHR need to file an 8-K and make an announcement? From a 2022 applicant registration listing both MNKD and UTHR. "The FDA has approved imatinib mesylate for the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors, relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), myelodysplastic/myeloproliferative diseases associated with platelet-derived growth factor receptor gene rearrangements, aggressive systemic mastocytosis without or an unknown D816V c-KIT mutation, hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (CHIC2 allele deletion) or FIP1L1-PDGFRα fusion kinase negative or unknown, unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans. |
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Post by hellodolly on Jul 25, 2023 10:16:30 GMT -5
As I linked to the site and went to the "Document" tab, scrolled down to the examiners "Non-Final Rejection" it looks as if their patent application is currently not valid as of May 17, 2023. Not sure if they have a case to appeal to the Patent Office?
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Post by neil36 on Jul 25, 2023 10:18:33 GMT -5
From the May 2022 conference call transcript:
Michael Castagna
Thank you everyone. So talking about the pipeline here; so we remain very excited about the pipeline. We talked about Afrezza and Tyvaso DPI and clofazimine. The next couple things we'll start to hear about over the coming quarters will imatinib going forward and the outcome of bleomycin model as well as DNA alpha and Thirona. These programs take a little more time in the beginning, and then once we get them through and get the CMC part working, these programs progress quite rapidly in the coming years.
Additionally, on the cannabinoid side, Receptor Life Sciences received FD – and IND for the FDA to progress their development. And we continue to keep in touch with Fosun around their small molecule inhibitor and how that's progressing in development. We'll continue to look for more collaborations on our technology platform as we continue move forward post the next FDA action date with Tyvaso. When we look at our milestones for 2022, we clearly lay out every year and you can see so far we're on track to meet and most of these milestones exceed them, we obviously did not hit the first one, which we think was very important on the Tyvaso DPI PDUFA date, that's been extended to May and we remain optimistic about that date and our ability to hopefully get Tyvaso to patients here in Q2.
So, one, I think important thing when we come to you on our next earning call will be two additional sources of revenue as related to out back in Q4 earning's call on Tyvaso manufacturing and Tyvaso royalties. The bars of revenue growth for MannKind continue to grow and we look very look – look out very forward about the exciting opportunities we have to exponential grow revenue over the coming years between Afrezza, collaboration services, business development as well as manufacturing and royalties.
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Post by peppy on Jul 25, 2023 10:21:02 GMT -5
Under back ground
"Imatinib functions as a specific inhibitor of a number of tyrosine kinase (TK) enzymes. It occupies the TK active site, leading to a decrease in activity. There are a large number of TK enzymes in the body, including the insulin receptor.
Imatinib is specific for the TK domain in abl (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor receptor). Aberrant expression and signaling of PDGF ligands and receptors is associated with several connective tissue disorders and lung diseases such as pulmonary arterial hypertension (PAH), lung cancer and idiopathic pulmonary fibrosis (IPF)."
Summary
In one embodiment, there is provided an inhaler, such as a dry powder inhaler, for delivering an inhalable pharmaceutical composition, such as a dry powder composition, comprising a therapeutically effective amount of imatinib, a pharmaceutically acceptable salt, or derivative thereof, and optionally one or more excipients. In some embodiments, the dry powder inhaler can be structurally configured to deliver the dry powder composition from a capsule or a cartridge which can be adapted or mounted in the inhaler.
In one embodiment, the dry powder inhaler can be breath-actuated or activated to initiate powder aerosolization within the inhaler during use and delivery of the dry powder pharmaceutical composition.
===============================================================================
(Keytruda has something like 30 indications. Just saying)
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Post by peppy on Jul 25, 2023 11:44:29 GMT -5
Similar to nintedanib? Already in the pipeline. No clue, however, Martine is in. Applicants United Therapeutics Corporation MannKind Corporation |
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Post by slapshot on Jul 25, 2023 12:51:41 GMT -5
As I linked to the site and went to the "Document" tab, scrolled down to the examiners "Non-Final Rejection" it looks as if their patent application is currently not valid as of May 17, 2023. Not sure if they have a case to appeal to the Patent Office? They get up to 6 months to respond to the non-final rejection. Its possible that they could amend the claims and/or argue as to why the rejection is not valid. The PTO would then reconsider and either allow the application or issue another rejection in which case they would get another 6 months to respond. |
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Post by peppy on Jul 25, 2023 13:20:24 GMT -5
Similar to nintedanib? Already in the pipeline. No clue, however, Martine is in. Applicants United Therapeutics Corporation MannKind Corporation I see your point as the suffix's match. Detailed description. Imatinib was first described in U.S. Pat. No. 5,521,184. US Patent Publication No. US20110190313A1 describes use of imatinib for treatment of pulmonary hypertension. US Patent Publication No. US20150044288A1 describes administration of imatinib by inhalation for treatment of pulmonary hypertension and other conditions. patentscope.wipo.int/search/en/detail.jsf?docId=US361308224&_cid=P20-LKID1O-54569-1 |
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Post by castlerockchris on Jul 25, 2023 14:14:27 GMT -5
Hopefully the fact that both MNKD and UTHR are listed in the application, if this moves forward and is successful, it will mean better than low double digit royalties for MNKD.
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Post by neil36 on Jul 25, 2023 15:46:15 GMT -5
A couple posters on StockTwits commenting that Mike confirmed that Imatinib is off the table. I can't find a transcript anywhere to confirm that. The only thing I could find was the May 2022 conference call where he said it in the works and we should be hearing more about it in the months ahead. If anyone has a quote where he said it is off the table, that would be helpful.
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Post by prcgorman2 on Jul 25, 2023 15:59:23 GMT -5
A couple posters on StockTwits commenting that Mike confirmed that Imatinib is off the table. I can't find a transcript anywhere to confirm that. The only thing I could find was the May 2022 conference call where he said it in the works and we should be hearing more about it in the months ahead. If anyone has a quote where he said it is off the table, that would be helpful. Any idea if the posters are reliable or just the usual, um, suspects, that prevent me from visiting stocktwits? |
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