RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:MTD and the FDAThere is no patent on isotopes or atoms. In the case of Lutathera, they have no patent on the peptide, the linker and the isotope. I think their patent is on the way to manufacture the PDC. I think they have a patent on use, but I am not sure it is valid since Lu177-Dotatate is used in Europe since at least 15 years. Many cancer centers in Europe were offering it a bit like a generic drug within some research or access programs, even though it was not formally approved by the EMA. Even here in Canada, it was accessible through some sort of clinical program approved by Health Canada just to make it accessible to patients needing it. Here is a link to an article in french (Google translate) about a patient badly wanting it in 2012. I think Health Canada made it accessible shortly after that.
https://www.journaldemontreal.com/2012/10/17/mourir-dans-lattente
But in the case of TH19P01, Thera have the patent on it. So using it with the linker DOTA and any isotope would make it a new chemical entity and they could have a strong a long patents on any of the combinations with Lutetium 177, Gallium 68 or Actinium 225.
Wino115 wrote: Dies that mean the competitor will have the peptide+Actinium patent for all cancers? Or would you still be able to conjugate it with something using different target than they use?
jfm1330 wrote: Yes but we are still a few years away to see an ADC or a PDC using it being approved. It's on trial with many ADC, and that's in line with the fact that ADC needs more potent cytotoxic agents since they have a low loading rate, and also low tumor penetration and cell internalization. But if it works for ADC, it should be a killer in a good PDC system (peptide + target). On the PDC front, they are working on it with Dotatate, the peptide + linker of Lutathera, they only real PDC that is approved. They simply replace Lutetium 177 by Actinium 225. But since the kind of radiation is different and the toxicity much higher, they need to redo the whole development process.
juniper88 wrote: Jfm1330, I like your actinium-225 idea. It can probably overcome any resistance mechanisms as long as it goes in the cancer cell.
jfm1330 wrote: Resistance to docetaxel can come from multiple modifications in gene expression. The MDR efflux pump involving p-glycoprotein seems to be the main one, and the one Thera claim Th1902 allows to bypass, but there are other mechanism of resistance at the tubulin level, which is the target of docetaxel. Also, some inefficacy can be related to dose limitation, or, in other words, the impossiblity to achieve an intracellular concentration of docetaxel that is high enough. A wider therapeutic window linked with the concentrating effect of TH1902 should help to achieve much greater docetaxel concentrations of TH1902. So that and bypassing the MDR efflux pump should allow efficacy on many resistant cancer types, but there will be some cancers where docetaxel will just be ineffective, no matter how high the intracellular concentration.
AMoschitto wrote: On this point, with patients who may have developed resistance to taxol based on their previous treatment history... would bypassing the MDR pump still be effective in the way they talked about in the June presentation? I went to look back at that slide but they have
taken it out of the current presentation.
Curious if people here have thoughts about that as a potential disadvantage of this population (of course acknowledging more sortilin expression in late-stage cancers as making these patients ideal for TH1902 as well).