6 ms·

The answer is phages. But last time I went into the rabbit hole the TLDR was that it is not patentable so there's no money in it. And everyone needs a different

The answer is phages. But last time I went into the rabbit hole the TLDR was that it is not patentable so there's no money in it. And everyone needs a different phages cocktail. I sleep at night knowing that push come to shove someone will step in and mass produce machines to create personal phage cocktails.

efields 4y ago
Is the implication here that antibiotics are more commercially viable, but phages are the real solution? I'm unfamiliar with phages, but a quick lookup revealed "virus that eats bacteria" and it's like, yeah… let's do that to combat bacterial infections. I'm guessing alignment between phage/bacteria is crucial.
- stackbutterflow 4y ago
  Someone can correct me if I'm wrong but what I got was that there's nothing to patent because phages are found in sewers and mud pools as is. Also every individual with a bacterial infection needs a custom cocktail so there's no one-size-fits-all pill that can be mass produced. Phages also have their own caveats but I don't remember what it is. The TLDR is that in the worst case scenario we still have phages and as far as I understand no bacteria can adapt to phages. But we need to figure out a way to make it commercially viable as you put it.
  - bee_rider 4y ago
    As someone who knows nothing about biology, this as well as the limited shelf-life issue mentioned in other comments makes me wonder if something like “A collection of less specialized phages and a process by which they can be quickly programmed to go after a bacteria” could be patented. I’m sure this is dumb because if it wasn’t somebody would have done it by now, though.
CollinEMac 4y ago
Could someone explain this to me like I'm 5?
- meindnoch 4y ago
  phages = bacteriophages = viruses that kill bacteria [1] There's an arms race between bacteria and humans: bacteria infect humans → humans develop antibiotics to kill bacteria → bacteria evolves resistance against antibiotics → humans develop new antibiotics to kill resistant bacteria → bacteria evolves resistance to new antibiotics → ... Developing more and more new antibiotics for resistant bacteria is slow and expensive. Bacteriophages (viruses that infect bacteria) on the other hand would naturally evolve with the bacteria, like how COVID evolved new strains in response to our vaccines. [1] https://en.wikipedia.org/wiki/Phage_therapy https://en.wikipedia.org/wiki/Phage_therapy
- Traubenfuchs 4y ago
  Not just higher life is plagued by viruses, bacteria as well. And bacteriophages are viruses that only target specific bacteria. They are among the most abundant "forms of life" in the whole world, as google details: > There are up to ten times more phages in the oceans than there are bacteria, reaching levels of 250 million bacteriophages per millilitre of seawater. If we were able to quickly find the right phage for bacteria that causes infection, that bacteria would have no chance. And we do know that for every bacteria there would be infinite phage variants they just can not defend themselves against by design. From what we know bacteria, all life in general will always stay vulnerable to viruses. The problem is that our science on finding, producing and using bacteriophages is extremely limited for technical and financial reasons.
  - hfsh 4y ago
    > by design Yeah, no. Quite the opposite in fact.
    - Traubenfuchs 4y ago
      All I wanted to say here was: Anything infectable by a virus can not become immune to viruses as a whole. There is always a new virus variant/mutation out there, or possible to come into existence, that kills the bacteria.
John23832 4y ago
Phages are not the silver bullet that people think they are. First they're difficult to make and store (antibiotics are mostly shelf stable... phages aren't). Second, they are not broad spectrum. Third, (at least in the US) phage therapy hasn't taken off because the initial forays into phages showed that they can cause reactions. Lastly, not all bacteria have phage counterparts. So if you even could use phages, you're looking at weeks of testing to determine what bacteria to target, before production. You could keep a library of phages for known bacteria, but that library would be highly specific.
- bratwurst3000 4y ago
  Isnt it that phages can be engeneered to a specific bacteria? Also the other way around. The can be programmed with the dna of the bacteria. So pcr the bacteria then make phages that atack them. My knowledge is bad . Could you elaborate where the engeneering problem is and the cost factors? Thanks
  - John23832 4y ago
    The problem is that they are highly specific. You would need the industrial machinery to manufacture a highly specific treatment. With anything in medicine/biology, specificity dramatically increases cost. There's also the pre-treatment testing that would be necessary to determine what to target. There's also the shipment of a bacterial specimen that would be used to create a phage (which is something we don't do currently... we'll ship a specimen to a testing center, best case). Those are two different bacterial specimens needed. Then you have to ship the phages back. Alive. Then store and administer then properly. People fail to take their antibiotics properly. They're going to royally screw up phages. What about bacteria that you can't culture (treponema pallidum, aka syphilis)? All of this is in contrast to antibiotics. Is it gram positive or gram negative? Treat. Did it work? Yes, good. No, treat again. Did it work? Yes, good. No, test for resistance. Move to a stronger antibiotic and repeat. You really don't even need to know what the exact bacteria is that you're targeting with antibiotics.
    - bratwurst3000 4y ago
omginternets 4y ago
>TLDR was that it is not patentable so there's no money in it. I think you are overlooking some of the major technical problems with phages. In no particular order: 1. The immune system develops antibodies for many phages. 2. Microbes develop resistance to phages. 3. Phage multiplication using host cell is a primary step for phage production, and this causes many (serious) adverse effects. 4. Only obligate lytic phages that lyse the bacterial cell directly instead of integrating its genome in bacterial DNA (temperate) are usable for phage therapy. Temperate phages play a major role in the exchange of genetic material between different bacterial strains and often contribute to the pathogenicity.
abeppu 4y ago
> I sleep at night knowing that push come to shove someone will step in and mass produce machines to create personal phage cocktails. Drug resistant bacteria are here. Hasn't push already come to shove? Phages are interesting, but given that there are substantial challenges on the road to making and administering them (and you can be in a race against the clock as someone's infection progresses), shouldn't we also be trying to use existing antibiotics far more strategically?
deleted 4y ago
[deleted]
ronsor 4y ago
Sounds like the solution is to kill patents so they can forget about money entirely.
- deleted 4y ago
  [deleted]
yawnxyz 4y ago
Yay another phage thread! Phages do work, and we've treated a small bunch of people at Phage Australia for our clinical trial. There's a few things about using phages for treatments I think everyone should be aware of: (1) phages work!! The physicians we work with (and ourselves) are surprised every time they work. It's just really labor and time-intensive. (2) if antibiotics are "bite sized snacks" then phages are like "getting a personalized chef - a course of phages should be highly personalized to the pathogens causing trouble, and sometimes the antibiotics. Too generic and it won't work. Too personalized and it's too expensive. Tricky balance. We're collecting data and trying to figure out what that balance is. Every patient is very different though and it's hard to draw conclusions and see patterns. (3) at Phage Australia we're not doing the cocktail approach — we're (trying to) assembling a library of phages that should be able to cover lots of common pathogens and local outbreaks. We work with antibiotic resistance reference labs and hopefully eventually get enough coverage, by building a library of phages that we can mix and match before we get an inquiry. The TGA is onboard with this. (The FDA is looking into this tentatively; look up Adaptive Phage Therapeutics). The kind of phage therapy we're looking at is closer to CAR T-cell therapy, FMT and other kinds of individual / personalized therapies. tl;dr: Phages work, but getting them and getting/paying for them is more like a service and less like a pill. It's also very expensive and hard to do today. We to work with regulators to push more personalized therapies. The age of generic pills in a bottle is slowly fading away. (Source: I'm the "computer person" aka research software engineer on the Phage Australia clinical trial)
- smallerfish 4y ago
  Are y'all using this for lyme disease? It seems like a billion dollar opportunity right there if somebody can make this reliable.
- dmix 4y ago
  I'm curious what drives customers to these services. Why would someone want to pay for a customized phage service? Someone who is taking lots of antibiotics or concerned about them?
  - deleted 4y ago
importantbrian 4y ago
Whenever someone says that the reason some health related thing isn't being used because it's not patentable and there's no money in it it's a pretty sure signal they don't know what they're talking about. Therapy methods, manufacturing methods, etc. are all patentable. As an example here is a patent that was granted around methods for selecting bacteriophages against specific bacteria [1]. If you search patent records for phage therapy there are tons of granted patents. The original patent for insulin was given away by it's discoverers because they wanted everyone to be able to have access to inexpensive insulin. That hasn't stopped pharma companies from coming up with patents around formulations, manufacturing methods, delivery methods, etc. and making tons of money off of insulin. Sibling comments have pointed out the real reasons it's not commonly used despite the promise. I just wanted to point out not being able to patent something is almost never a barrier for pharmaceutical companies if they think they can come up with a profitable therapeutic. [1] https://patents.google.com/patent/US10357522B2/en?q=phage+therepy&oq=phage+therepy&clustered=true https://patents.google.com/patent/US10357522B2/en?q=phage+th...
- stackbutterflow 4y ago
  Yes, I don't know what I'm talking about. As I said I went into a rabbit hole and provided a TLDR. But do these guys know what they're talking about? https://phage.directory/capsid/phage-patentability https://phage.directory/capsid/phage-patentability You may have heard through the grapevine that “phages can’t be patented”, and yet, several phage patents exist, and biotech and pharma are starting to invest in phage-based therapeutics. What’s the deal? [...] However, the patentability of phage therapies has been called into question. Several patents in the same category as phages have actually failed to hold up in court. This suggests that even if companies can find ways to successfully file phage patents, these patents may end up being worthless. So phages may need protection in other ways.
  - importantbrian 4y ago
    I think they might not. I will grant I'm not an expert in this area, but I did read the cited paper. It's a paper from a law student published in the universities law journal. Maybe he knows what he's talking about, but I would put my money on the patent attorneys filing and being granted all the phage therapy patents. It was also published in 2019 and a lot of phage related patents have been granted since then. Is the patent office just unaware of the precedence cited in the paper? Are there any examples of phage therapy patents being challenged in court and not holding up? Here is some info from a leading IP firm on the challenges around phage patents and how to address them when filing [1]. As they pretty clearly point out there are some challenges, but creating defensible patents in this area can be and is done. These companies can pretty much always find a way to create a defensible patent if they want to. [1] https://www.nixonpeabody.com/insights/alerts/2021/03/03/patent-update-bacteriophage-applications https://www.nixonpeabody.com/insights/alerts/2021/03/03/pate...

efields 4y ago

Is the implication here that antibiotics are more commercially viable, but phages are the real solution? I'm unfamiliar with phages, but a quick lookup revealed "virus that eats bacteria" and it's like, yeah… let's do that to combat bacterial infections. I'm guessing alignment between phage/bacteria is crucial.

stackbutterflow 4y ago
Someone can correct me if I'm wrong but what I got was that there's nothing to patent because phages are found in sewers and mud pools as is. Also every individual with a bacterial infection needs a custom cocktail so there's no one-size-fits-all pill that can be mass produced. Phages also have their own caveats but I don't remember what it is. The TLDR is that in the worst case scenario we still have phages and as far as I understand no bacteria can adapt to phages. But we need to figure out a way to make it commercially viable as you put it.
- bee_rider 4y ago
  As someone who knows nothing about biology, this as well as the limited shelf-life issue mentioned in other comments makes me wonder if something like “A collection of less specialized phages and a process by which they can be quickly programmed to go after a bacteria” could be patented. I’m sure this is dumb because if it wasn’t somebody would have done it by now, though.

CollinEMac 4y ago

Could someone explain this to me like I'm 5?

meindnoch 4y ago
phages = bacteriophages = viruses that kill bacteria [1] There's an arms race between bacteria and humans: bacteria infect humans → humans develop antibiotics to kill bacteria → bacteria evolves resistance against antibiotics → humans develop new antibiotics to kill resistant bacteria → bacteria evolves resistance to new antibiotics → ... Developing more and more new antibiotics for resistant bacteria is slow and expensive. Bacteriophages (viruses that infect bacteria) on the other hand would naturally evolve with the bacteria, like how COVID evolved new strains in response to our vaccines. [1] https://en.wikipedia.org/wiki/Phage_therapy https://en.wikipedia.org/wiki/Phage_therapy
Traubenfuchs 4y ago
Not just higher life is plagued by viruses, bacteria as well. And bacteriophages are viruses that only target specific bacteria. They are among the most abundant "forms of life" in the whole world, as google details: > There are up to ten times more phages in the oceans than there are bacteria, reaching levels of 250 million bacteriophages per millilitre of seawater. If we were able to quickly find the right phage for bacteria that causes infection, that bacteria would have no chance. And we do know that for every bacteria there would be infinite phage variants they just can not defend themselves against by design. From what we know bacteria, all life in general will always stay vulnerable to viruses. The problem is that our science on finding, producing and using bacteriophages is extremely limited for technical and financial reasons.
- hfsh 4y ago
  > by design Yeah, no. Quite the opposite in fact.
  - Traubenfuchs 4y ago
    All I wanted to say here was: Anything infectable by a virus can not become immune to viruses as a whole. There is always a new virus variant/mutation out there, or possible to come into existence, that kills the bacteria.

John23832 4y ago

Phages are not the silver bullet that people think they are. First they're difficult to make and store (antibiotics are mostly shelf stable... phages aren't). Second, they are not broad spectrum. Third, (at least in the US) phage therapy hasn't taken off because the initial forays into phages showed that they can cause reactions. Lastly, not all bacteria have phage counterparts. So if you even could use phages, you're looking at weeks of testing to determine what bacteria to target, before production. You could keep a library of phages for known bacteria, but that library would be highly specific.

bratwurst3000 4y ago
Isnt it that phages can be engeneered to a specific bacteria? Also the other way around. The can be programmed with the dna of the bacteria. So pcr the bacteria then make phages that atack them. My knowledge is bad . Could you elaborate where the engeneering problem is and the cost factors? Thanks
- John23832 4y ago
  The problem is that they are highly specific. You would need the industrial machinery to manufacture a highly specific treatment. With anything in medicine/biology, specificity dramatically increases cost. There's also the pre-treatment testing that would be necessary to determine what to target. There's also the shipment of a bacterial specimen that would be used to create a phage (which is something we don't do currently... we'll ship a specimen to a testing center, best case). Those are two different bacterial specimens needed. Then you have to ship the phages back. Alive. Then store and administer then properly. People fail to take their antibiotics properly. They're going to royally screw up phages. What about bacteria that you can't culture (treponema pallidum, aka syphilis)? All of this is in contrast to antibiotics. Is it gram positive or gram negative? Treat. Did it work? Yes, good. No, treat again. Did it work? Yes, good. No, test for resistance. Move to a stronger antibiotic and repeat. You really don't even need to know what the exact bacteria is that you're targeting with antibiotics.
  - bratwurst3000 4y ago

omginternets 4y ago

>TLDR was that it is not patentable so there's no money in it. I think you are overlooking some of the major technical problems with phages. In no particular order: 1. The immune system develops antibodies for many phages. 2. Microbes develop resistance to phages. 3. Phage multiplication using host cell is a primary step for phage production, and this causes many (serious) adverse effects. 4. Only obligate lytic phages that lyse the bacterial cell directly instead of integrating its genome in bacterial DNA (temperate) are usable for phage therapy. Temperate phages play a major role in the exchange of genetic material between different bacterial strains and often contribute to the pathogenicity.

abeppu 4y ago

> I sleep at night knowing that push come to shove someone will step in and mass produce machines to create personal phage cocktails. Drug resistant bacteria are here. Hasn't push already come to shove? Phages are interesting, but given that there are substantial challenges on the road to making and administering them (and you can be in a race against the clock as someone's infection progresses), shouldn't we also be trying to use existing antibiotics far more strategically?

deleted 4y ago

[deleted]

ronsor 4y ago

Sounds like the solution is to kill patents so they can forget about money entirely.

deleted 4y ago
[deleted]

yawnxyz 4y ago

Yay another phage thread! Phages do work, and we've treated a small bunch of people at Phage Australia for our clinical trial. There's a few things about using phages for treatments I think everyone should be aware of: (1) phages work!! The physicians we work with (and ourselves) are surprised every time they work. It's just really labor and time-intensive. (2) if antibiotics are "bite sized snacks" then phages are like "getting a personalized chef - a course of phages should be highly personalized to the pathogens causing trouble, and sometimes the antibiotics. Too generic and it won't work. Too personalized and it's too expensive. Tricky balance. We're collecting data and trying to figure out what that balance is. Every patient is very different though and it's hard to draw conclusions and see patterns. (3) at Phage Australia we're not doing the cocktail approach — we're (trying to) assembling a library of phages that should be able to cover lots of common pathogens and local outbreaks. We work with antibiotic resistance reference labs and hopefully eventually get enough coverage, by building a library of phages that we can mix and match before we get an inquiry. The TGA is onboard with this. (The FDA is looking into this tentatively; look up Adaptive Phage Therapeutics). The kind of phage therapy we're looking at is closer to CAR T-cell therapy, FMT and other kinds of individual / personalized therapies. tl;dr: Phages work, but getting them and getting/paying for them is more like a service and less like a pill. It's also very expensive and hard to do today. We to work with regulators to push more personalized therapies. The age of generic pills in a bottle is slowly fading away. (Source: I'm the "computer person" aka research software engineer on the Phage Australia clinical trial)

smallerfish 4y ago
Are y'all using this for lyme disease? It seems like a billion dollar opportunity right there if somebody can make this reliable.
dmix 4y ago
I'm curious what drives customers to these services. Why would someone want to pay for a customized phage service? Someone who is taking lots of antibiotics or concerned about them?
- deleted 4y ago

importantbrian 4y ago

Whenever someone says that the reason some health related thing isn't being used because it's not patentable and there's no money in it it's a pretty sure signal they don't know what they're talking about. Therapy methods, manufacturing methods, etc. are all patentable. As an example here is a patent that was granted around methods for selecting bacteriophages against specific bacteria [1]. If you search patent records for phage therapy there are tons of granted patents. The original patent for insulin was given away by it's discoverers because they wanted everyone to be able to have access to inexpensive insulin. That hasn't stopped pharma companies from coming up with patents around formulations, manufacturing methods, delivery methods, etc. and making tons of money off of insulin. Sibling comments have pointed out the real reasons it's not commonly used despite the promise. I just wanted to point out not being able to patent something is almost never a barrier for pharmaceutical companies if they think they can come up with a profitable therapeutic. [1] https://patents.google.com/patent/US10357522B2/en?q=phage+therepy&oq=phage+therepy&clustered=true https://patents.google.com/patent/US10357522B2/en?q=phage+th...

stackbutterflow 4y ago
Yes, I don't know what I'm talking about. As I said I went into a rabbit hole and provided a TLDR. But do these guys know what they're talking about? https://phage.directory/capsid/phage-patentability https://phage.directory/capsid/phage-patentability You may have heard through the grapevine that “phages can’t be patented”, and yet, several phage patents exist, and biotech and pharma are starting to invest in phage-based therapeutics. What’s the deal? [...] However, the patentability of phage therapies has been called into question. Several patents in the same category as phages have actually failed to hold up in court. This suggests that even if companies can find ways to successfully file phage patents, these patents may end up being worthless. So phages may need protection in other ways.
- importantbrian 4y ago
  I think they might not. I will grant I'm not an expert in this area, but I did read the cited paper. It's a paper from a law student published in the universities law journal. Maybe he knows what he's talking about, but I would put my money on the patent attorneys filing and being granted all the phage therapy patents. It was also published in 2019 and a lot of phage related patents have been granted since then. Is the patent office just unaware of the precedence cited in the paper? Are there any examples of phage therapy patents being challenged in court and not holding up? Here is some info from a leading IP firm on the challenges around phage patents and how to address them when filing [1]. As they pretty clearly point out there are some challenges, but creating defensible patents in this area can be and is done. These companies can pretty much always find a way to create a defensible patent if they want to. [1] https://www.nixonpeabody.com/insights/alerts/2021/03/03/patent-update-bacteriophage-applications https://www.nixonpeabody.com/insights/alerts/2021/03/03/pate...