Open Norway: Plasma cell aimed treatment with daratumumab in ME/CFS - Haukeland University Hospital
- Thread starter Kalliope
- Start date
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- cd38 daratumumab norway
Kitty
Senior Member (Voting Rights)
I think orphan drug status is about rare diseases, and might give the manufacturer rights to an exclusive licence, that kind of thing. It's an incentive to keep producing it and monitoring it, even if it's not very profitable because the patient pool is so small.
But ME/CFS probably wouldn't qualify as a rare disease, so that type of condition might not apply.
Yann04
Senior Member (Voting Rights)
Probably? It depends. It means anyone is allowed to manufacture it so that often means -> competition -> reduction in price. But not necessarily.
Utsikt
Senior Member (Voting Rights)
I might be completely wrong about this due to my lack of legal expertise, but I believe that the patent that expires March 2026 in Europe is for the drug itself. Some of the patents that expire later are for use cases of the drug.
Fluge and Mella have the patent application for Dara and many more -mabs for the treatment of ME/CFS:
Fluge and Mella have the patent application for Dara and many more -mabs for the treatment of ME/CFS:
Claims:
1. A method for the treatment of myalgic encephalomyelitis (ME)/chronic fa tigue syndrome (CFS) comprising administering to a patient in need thereof a therapeutically effective amount of an inhibitory or cytotoxic agent against plasma cells to reduce antibody production.
2. The method according to claim 1 wherein the inhibitory agent or cytotoxic agent against plasma cells to reduce antibody production is not an agent being an antibody directed against CD20, like Rituximab.
3. The method for the treatment of ME/CFS according to claim 1 or 2 where in said inhibitory agent against plasma cells is an inhibitor of the pro- teasome, like the immunoproteasome.
4. The method for the treatment of ME/CFS according to claim 3 wherein the inhibitor of the proteasome is selected from the group of Bortezomib, Car- filzomib, Ixazomib, Oprozomib, Delanzomib, Marizomib.
5. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein the cytotoxic agent against plasma cells is an anti body, like a monoclonal antibody, having cytotoxic activity against plasma cells.
6. The method for the treatment of ME/CFS according to claim 5 wherein said antibodies, like monoclonal antibodies including humanized monoclo nal antibodies, are antibodies directed against CD38 and/or CD319.
7. The method for the treatment of ME/CFS according to claim 6 wherein the CD38 monoclonal antibody is Daratumumab, Isatuximab, MOR202, TAK- 079 or wherein the monoclonal antibody directed against CD319 (SLAMF7) is Elotuzumab.
8. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said agents are adapted for systemic administra tion.
9. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said compounds are adapted for administration to a subject in single therapeutically effective daily doses thereof or multiple of therapeutically effective daily doses.
10. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said compounds are administered in a pharmaceu tically effective dosage systemically.
11. The method according to any one of the preceeding claims wherein the plasma cells are CD20 negative plasma cells not including plasmablasts, in particular, terminally differentiated plasma cells not expressing CD20.
12. The method for the treatment of ME/CFS according to any one of the pre ceding claims where the inhibitory or cytotoxic agents against plasma cells are employed in combination with a B-cell depleting agent, or an inhibitor of B-cell activation.
13. The method for the treatment of ME/CFS according to claim 12 wherein the B-cell depleting agent is a B-cell depleting anti-CD20 antibody or CD20 binding antibody fragment thereof, preferably, a monoclonal anti body or a CD20 binding antibody fragment thereof, like a humanized anti body or antibody fragment thereof, or wherein the B-cell depleting agent is a cytotoxic drug like cyclophosphamide, or wherein the inhibitor of B-cell activation is a Bruton Tyrosine Kinase (BTK) inhibitor, or wherein the in hibitor of B-cell activation is an anti B-cell activating factor (anti-BAFF) an tibody.
14. The method for the treatment of ME/CFS according to any one of claims 12 or 13 wherein the B-cell depleting agent is adapted for administration of one or two infusions twice within two weeks.
15. The method for the treatment of ME/CFS according to any one of claims 12 to 14 wherein the inhibition or cytotoxic agents against plasma cells and the B-cell depleting agent are administered simultaneously, separate ly or sequentially to a subject suffering from chronic fatigue syndrome.
16. The method for the treatment of ME/CFS according to any one of claims 12 to 15 wherein the inhibitory or cytostatic agent against plasma cells is administered subcutaneously, intravenously or orally, and the CD20 B-cell depleting agent or inhibitor of B-cell activation is administered subcutane ously, intravenously or orally.
17. The method for the treatment of ME/CFS according to any one of claims 12 to 16 wherein the B-cell depleting anti-CD20 antibody is selected from Rituximab, Ocrelizumab, Obinutuzumab, Veltuzumab, Ofatumumab, or wherein the inhibitor of B-cell activation is selected from Bruton Tyrosine Kinase (BTK) inhibitors such as Ibrutininb, Evobrutinib, or AVL-292, GDC- 0834, ONO-WG-307, Dasatinib, or wherein the inhibitor of B-cell activation is selected from anti B-cell activating factor (anti-BAFF) antibodies such as Belimumab or Tabalumab, or wherein the inhibitor of B-cell activation is selected from cytotoxic drugs like Cyclophosphamide.
18. The method according to any one of claims 12 to 17 wherein the inhibitory or cytotoxic agent against plasma cells is administered first in a first treatment regimen and, after a period of time without treatment will the in hibitory or cytotoxic agent against plasma cells, the B-cell depleting agent, in particular, an anti-CD20 antibody or CD20 binding antibody fragment is administered for a further period of time.
19. The method according to claim 18 wherein the first therapy regimen with administering the inhibitory or cytotoxic agent against plasma cells com prises at least two courses of treatment with the inhibitory or cytotoxic agent against plasma cells and, thereafter, with a period of time with no treatment regimen, administering at least two courses of anti-CD20 anti body or CD20 binding antibody fragment thereof.
20. An inhibitory or cytotoxic agent against plasma cells as defined in any one of claims 1 to 8 for use in the treatment of chronic fatigue syndrome.
21. A composition containing a combination of i) an inhibitory or cytotoxic agent against plasma cells and ii) a B-cell depleting agent, in particular, a B-cell depleting anti-CD20 antibody, or an inhibitor of B-cell activation such as a Bruton Tyrosine Kinase (BTK) inhibitor, or an inhibitor of B-cell activation such as an anti-BAFF antibody, or an inhibitor of B-cell prolifer ation such as a cytotoxic drug like Cyclophosphamide.
22. The composition according to claim 21 for use in the treatment of ME / CFS.
23. The composition for use according to claim 22 wherein the inhibitory or cytotoxic agent against plasma cells is administered in a first step and the B-cell depleting agent is administered thereafter in a second step.
24. The composition for use according to any one of claims 22 to 23 wherein the inhibitory or cytotoxic agent against plasma cells is an inhibitor of the proteasome, in particular, Bbortezomib, and the B-cell depleting agent is a B-cell depleting anti-CD20 antibody, in particular, Rituximab, Ocrelizumab, Obinutuzumab, Veltuzumab, Ofatumumab.
1. A method for the treatment of myalgic encephalomyelitis (ME)/chronic fa tigue syndrome (CFS) comprising administering to a patient in need thereof a therapeutically effective amount of an inhibitory or cytotoxic agent against plasma cells to reduce antibody production.
2. The method according to claim 1 wherein the inhibitory agent or cytotoxic agent against plasma cells to reduce antibody production is not an agent being an antibody directed against CD20, like Rituximab.
3. The method for the treatment of ME/CFS according to claim 1 or 2 where in said inhibitory agent against plasma cells is an inhibitor of the pro- teasome, like the immunoproteasome.
4. The method for the treatment of ME/CFS according to claim 3 wherein the inhibitor of the proteasome is selected from the group of Bortezomib, Car- filzomib, Ixazomib, Oprozomib, Delanzomib, Marizomib.
5. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein the cytotoxic agent against plasma cells is an anti body, like a monoclonal antibody, having cytotoxic activity against plasma cells.
6. The method for the treatment of ME/CFS according to claim 5 wherein said antibodies, like monoclonal antibodies including humanized monoclo nal antibodies, are antibodies directed against CD38 and/or CD319.
7. The method for the treatment of ME/CFS according to claim 6 wherein the CD38 monoclonal antibody is Daratumumab, Isatuximab, MOR202, TAK- 079 or wherein the monoclonal antibody directed against CD319 (SLAMF7) is Elotuzumab.
8. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said agents are adapted for systemic administra tion.
9. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said compounds are adapted for administration to a subject in single therapeutically effective daily doses thereof or multiple of therapeutically effective daily doses.
10. The method for the treatment of ME/CFS according to any one of the pre ceding claims wherein said compounds are administered in a pharmaceu tically effective dosage systemically.
11. The method according to any one of the preceeding claims wherein the plasma cells are CD20 negative plasma cells not including plasmablasts, in particular, terminally differentiated plasma cells not expressing CD20.
12. The method for the treatment of ME/CFS according to any one of the pre ceding claims where the inhibitory or cytotoxic agents against plasma cells are employed in combination with a B-cell depleting agent, or an inhibitor of B-cell activation.
13. The method for the treatment of ME/CFS according to claim 12 wherein the B-cell depleting agent is a B-cell depleting anti-CD20 antibody or CD20 binding antibody fragment thereof, preferably, a monoclonal anti body or a CD20 binding antibody fragment thereof, like a humanized anti body or antibody fragment thereof, or wherein the B-cell depleting agent is a cytotoxic drug like cyclophosphamide, or wherein the inhibitor of B-cell activation is a Bruton Tyrosine Kinase (BTK) inhibitor, or wherein the in hibitor of B-cell activation is an anti B-cell activating factor (anti-BAFF) an tibody.
14. The method for the treatment of ME/CFS according to any one of claims 12 or 13 wherein the B-cell depleting agent is adapted for administration of one or two infusions twice within two weeks.
15. The method for the treatment of ME/CFS according to any one of claims 12 to 14 wherein the inhibition or cytotoxic agents against plasma cells and the B-cell depleting agent are administered simultaneously, separate ly or sequentially to a subject suffering from chronic fatigue syndrome.
16. The method for the treatment of ME/CFS according to any one of claims 12 to 15 wherein the inhibitory or cytostatic agent against plasma cells is administered subcutaneously, intravenously or orally, and the CD20 B-cell depleting agent or inhibitor of B-cell activation is administered subcutane ously, intravenously or orally.
17. The method for the treatment of ME/CFS according to any one of claims 12 to 16 wherein the B-cell depleting anti-CD20 antibody is selected from Rituximab, Ocrelizumab, Obinutuzumab, Veltuzumab, Ofatumumab, or wherein the inhibitor of B-cell activation is selected from Bruton Tyrosine Kinase (BTK) inhibitors such as Ibrutininb, Evobrutinib, or AVL-292, GDC- 0834, ONO-WG-307, Dasatinib, or wherein the inhibitor of B-cell activation is selected from anti B-cell activating factor (anti-BAFF) antibodies such as Belimumab or Tabalumab, or wherein the inhibitor of B-cell activation is selected from cytotoxic drugs like Cyclophosphamide.
18. The method according to any one of claims 12 to 17 wherein the inhibitory or cytotoxic agent against plasma cells is administered first in a first treatment regimen and, after a period of time without treatment will the in hibitory or cytotoxic agent against plasma cells, the B-cell depleting agent, in particular, an anti-CD20 antibody or CD20 binding antibody fragment is administered for a further period of time.
19. The method according to claim 18 wherein the first therapy regimen with administering the inhibitory or cytotoxic agent against plasma cells com prises at least two courses of treatment with the inhibitory or cytotoxic agent against plasma cells and, thereafter, with a period of time with no treatment regimen, administering at least two courses of anti-CD20 anti body or CD20 binding antibody fragment thereof.
20. An inhibitory or cytotoxic agent against plasma cells as defined in any one of claims 1 to 8 for use in the treatment of chronic fatigue syndrome.
21. A composition containing a combination of i) an inhibitory or cytotoxic agent against plasma cells and ii) a B-cell depleting agent, in particular, a B-cell depleting anti-CD20 antibody, or an inhibitor of B-cell activation such as a Bruton Tyrosine Kinase (BTK) inhibitor, or an inhibitor of B-cell activation such as an anti-BAFF antibody, or an inhibitor of B-cell prolifer ation such as a cytotoxic drug like Cyclophosphamide.
22. The composition according to claim 21 for use in the treatment of ME / CFS.
23. The composition for use according to claim 22 wherein the inhibitory or cytotoxic agent against plasma cells is administered in a first step and the B-cell depleting agent is administered thereafter in a second step.
24. The composition for use according to any one of claims 22 to 23 wherein the inhibitory or cytotoxic agent against plasma cells is an inhibitor of the proteasome, in particular, Bbortezomib, and the B-cell depleting agent is a B-cell depleting anti-CD20 antibody, in particular, Rituximab, Ocrelizumab, Obinutuzumab, Veltuzumab, Ofatumumab.
WO2021038097A1 - Method for the treatment of chronic fatigue syndrome using an inhibitory or cytotoxic agent against plasma cells - Google Patents
The present invention relates in a first aspect to a method for the treatment of chronic fatigue syndrome (CFS) comprising administering to a patient in need thereof a therapeutically effective amount of inhibitory or cytotoxic agent against plasma cells. In a further aspect, the present...
patents.google.com
Yann04
Senior Member (Voting Rights)
Why would Fluge and Mella make that patent? Just to profit from it if it works out?
Sasha
Senior Member (Voting Rights)
I don't really understand the implications of all this... does it mean the current trial might suddenly get cheaper? Or be brought to a halt if the current manufacturer decides it's no longer worth producing?
Kitty
Senior Member (Voting Rights)
If a drug is out of patent, anybody with the right pharma licence can make it. Then market forces come into play; competition forces the price down. With common drugs like ibuprofen, the price can halve overnight and then continue to come down if there's a lot of demand for it.
But I'm not sure about it making the trial a lot cheaper. A very big chunk of the budget is likely to be salaries, and that won't change.
Kitty
Senior Member (Voting Rights)
There might be some technical reasons for it that are hard to second guess.
But if there is money to be made from patenting a treatment, there's a perfectly good argument for the academic centre that's supported this work, probably at its own cost, to receive some recompense. And the clinicians involved, who've taken significant professional risks.
I don't think it means they're hoping to make squillions and retire to their mansions on private Caribbean islands.
OrganicChilli
Senior Member (Voting Rights)
My understanding is that the patent for daratumumab, the active ingredient, runs out next year, but the patent for Darzalex, which is the drug given intravenously or subcutaneously, lasts until the 2030s. A trial for a biosimilar of the subcutaneous form is still under way but and will conclude roughly at the same time as the F/M study. So while F/M are using Darzalex, the price won't come down.
Utsikt
Senior Member (Voting Rights)
The only reason to patent something is to earn money from it. What that money will be used for is a different question. An idealist might hope it would be used to fund more research.
Do you remember the source?
Utsikt
Senior Member (Voting Rights)
Thank you!
It says «if granted».
There might be more to this, but I found this press release saying that a patent for subcutaneous Dara was revoked in EU late 2024.
OrganicChilli
Senior Member (Voting Rights)
What's a proteasome and why would we want to inhibit it? Chatgpt says it has nothing to do with CD38. So are you suggesting an alternative pathway?
hotblack
Senior Member (Voting Rights)
That isn’t always the case. There are other reasons. You could even patent something and give it away, to ensure nobody else patents it and charges or even withholds it. Not saying that is the case here. Just that we don’t know the reasons. It would be good to of course.
Utsikt
Senior Member (Voting Rights)
You can’t patent something that someone else has invented before you, so that argument doesn’t hold.
Fluge and Mella can always chose to not enforce the patent, the patent only gives them the right to enforce it, not a duty to enforce it.
They could give or sell it to someone else that intends to enforce it, but that would just change who makes the money off of it.
You could technically argue that an existing patent makes it impossible for someone else to get a patent for the same thing in case the patent authority wasn’t aware of their intervention, but that’s probably an unlikely situation.
Yann04
Senior Member (Voting Rights)
Yeah in that case an Open Patent, or Patentleft (https://en.wikipedia.org/wiki/Patentleft?wprov=sfti1) would have made more sense.
Utsikt
Senior Member (Voting Rights)
Ooh, that’s a cool concept.
So I stand corrected: there might be a way to use patents to ensure other patents based on the original patents are not being used to generate money.
Although I’m not sure how that works if your original patent is build upon another for-profit patent. But we’re getting off track from the side-track of the Dara patent relating to this trial specifically..
jnmaciuch
Senior Member (Voting Rights)
proteasome is the cell’s garbage disposal. PIs are particularly good at killing cancerous plasma cells since the process of making immunoglobulins is intensive, and if a cell can’t turn over those proteins fast enough they will build up and cause the cell to die (at least that’s the current thinking of why they work).
I think the idea here is that using a proteasome inhibitor would confirm whether any potential beneficial effect from Dara comes from targetting CD38 on plasma cells specifically or from blocking CD38’s other enzymatic functions.
Kitty
Senior Member (Voting Rights)
The reason could be something as boring as a condition of grant, or that their institution requires researchers to do it as a matter of course.