Going through the Follica Patent, highlighting the important stuff

Stem cell; cell based hair therapy
1

Here is what jumps out at me…

How to “handle the skin” post wounding according to the patent:

"Optionally, the skin, following the epidermal disruption, is not contacted for a period of time with any substance (e.g., ointment, a bandage, or a device) that is normally administered to an abrasion or wound to prevent infection.

Here the skin is not contacted with any substance until, for example, the ■ •■ - epidermal disruption -has healed (e.g., any time between 2 days and 3 weeks). Alternatively, the skin can be contacted with a cast or bandage (e.g., resulting in increased blood flow to the disrupted skin or decreased transdermal water loss or decreased mass transfer of gases into the skin and from the skin (e.g. oxygen, carbon dioxide, water vapor), decreased heat transfer from the skin (e.g. resulting in an increased temperature of the skin surface) or increased pressure on the skin."

What is the simpleist embodiment of the patent?

“In a particular embodiment of the methods, kits, and compositions of the invention, the EGFR inhibitor is administered, formulated, or is part of a kit with an anti-androgen (e.g., finasteride ) and a channel opener (e.g., minoxidil).”

What is the most important ingredient in the patent?

“of a small molecule EGFR inhibitor formulated for topical administration, wherein the EGFR inhibitor is a non-naturally occurring nitrogen-including heterocycle of less than about 2,000 daltons, or a metabolite thereof”

What will probably be included in the “Kit”?

The invention further features a kit including a composition formulated for topical administration including (i) a small molecule EGFR inhibitor selected from leflunomide, gefitinib, erlotinib, lapatinib, canertinib, vandetanib, CL-387785, PKI166, pelitinib, HKI-272, and HKI-357; and (ii) an additional biologically active agent selected from an antihistamine, an anti-inflammatory, a retinoid, an anti-androgen, an immunosuppressant, a channel opener, an antibiotic, and an antimicrobial. In one embodiment, the small molecule EGFR inhibitor is gefitinib or erlotinib and the additional biologically active agent is a channel opener selected from minoxidil, diazoxide, and phenytoin

What is the treatment schedule?

The invention features a method for generating a hair follicle or stimulating a hair growth on the skin of a subject by (i) disrupting the skin of the subject (for example, resulting in the induction of reepithelialization of the skin of the subject) and (ii) contacting the cells of the skin with a small molecule EGFR inhibitor, or a metabolite thereof, in an amount sufficient to generate hair follicles or stimulate hair growth on the skin. In certain embodiments, step (a) is performed less than two weeks, 10 days, 8 days, 5 days, or even 3 days prior to step (b). In other embodiments, step (a) is performed simultaneous with, or more than one day, two days, 3 days or one week after step

How long will you be using medication?
…for applying the composition to the skin of a subject once or twice daily, for applying the composition to the skin of a subject for at least 2, 3, 4, 5, 6, 7, 8, 9, or even 10 consecutive days

or
■ after completion of the reepithelialization process (e.g., 3-12 days, or 9- 11 days after having disrupted the skin),

Keep this in mind:

The invention features a kit including (i) a composition of the invention; and (ii) instructions for administration of the composition to the skin of a subject, wherein the skin has undergone reepithelialization less than two weeks prior to the first administration of the composition

How big and deep are the “wounds” going to be from the dermabrasion?

The depth of skin disruption can include in increasing amounts: partial removal of the stratum corneum, complete removal of the stratum corneum, partial removal of the epidermis, complete removal of the epidermis, partial disruption of the dermis and complete removal of the dermis. Skin disruption can also include disruption of the mid to lower epidermis and/or dermis without any disturbance to the stratum- corneum and/or outer epidermis. Different levels of skin disruption • can be accomplished by chemical, energetic, mechanical, sound, ultrasound, and/or electromagnetic based methods

The area of reepithelialization can be, for example, between 0-2 millimeteres (mm) in width (e.g., 1 mm, 2 mm, 3 mπij or greater), 0-2 centimeters (cm) in width (e.g., 1 cm, 1.5 cm, and 2.0 cm) or greater. Optionally, the area of reepithelialization can be interfollicular. In some aspects of the invention, it is desirable to administer the compounds of the invention at a particular phase of reepithelialization. Stages at which compounds of the invention may preferably be administered and/or activated include periods:

How many ways can a state of re-epilithialization be induced:

The state of reepithelialization can be induced. Methods of inducing this state include the disruption of the subject’s skin at the location where the compounds of the invention are going to be administered. Disruption can be achieved through abrasion (e.g., the rubbing or wearing away of skin), or through any method that results in disturbing the intactness of the epidermis or epidermal layer including burning (e.g., by inducing a sunburn) or perforating the epidermis or epidermal -layer: The disruption can either result in partial or complete removal of the epidermal layer at the intended location.

The disruption of the epithelial layer can be accomplished, for example, through mechanical, chemical, electromagnetic, electrical, or magnetic means. Mechanical means can be achieved through the use of, for example, sandpaper, a felt wheel, ultrasound, supersonically accelerated mixture of saline and oxygen, tape-stripping, or peels.

Chemical means of disruption of the epidermis can be achieved, for example, using phenol, trichloracetic acid, or ascorbic acid.

Electromagnetic means of disruption of the epidermis can be achieved, for example, by the use of a laser capable of inducing trans-epithelial injury (e.g., a Fraxel laser, a CO2 laser, or an excimer laser). Disruption can also be achieved through, for example, the use of visible, infrared, ultraviolet, radio, or X-ray irradiation.

Electrical or magnetic means of disruption of the epidermis can be achieved, for example, through the application of an electrical current or through electroporation. Electric or magnetic means can also include the induction of an electric or a magnetic field. For example, an electrical current

can be induced in the skin by application of an alternating magnetic field. A radiofrequency power source can be coupled to a conducting element, and the currents that are induced will heat the skin, resulting in an alteration or disruption of the skin. In this embodiment, no external energy transfer is needed in order to cause a disruptio

What are the various possible substances that could be used from day 3-10 post wounding for intstance?

anti-androgen (e.g., finasteride, flutamide, diazoxide, l lalpha-hydroxyprogesterone, ketoconazole, RU58841, dutasteride, fluridil, and QLT-7704), an immunosuppressant (e.g., cyclosporine, tacrolimus, rapamycin, everolimus, and pimecrolimus), a channel opener (e.g., minoxidil, diazoxide, and phenytoin), an antibiotic, and an antimicrobial (e.g., benzyl benzoate, benzalkonium chloride, benzoic acid, benzyl alcohol, butylparaben, ethylparaben, methylparaben, propylparaben, camphorated metacresol, camphorated phenol, hexylresorcinol, methylbenzethonium chloride, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, glycerin, imidurea, phenol, phenoxyethanol, phenylethylalcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, sodium benzoate, sodium proprionate, sorbic acid, and thiomersal

Make it as simple as possible:

The invention features a kit including (i) a composition of the invention; and (ii) instructions for administration of the composition to the skin of a subject, wherein the skin has undergone reepithelialization less than two weeks prior to the first administration of the composition

2

A few more things…

This is what it looks like to me folks:

They might depilate the existing hair, and then wait three days.

They wound (abrade) and wait at least three more days and possibly about five or six

They start with the topical or with the internals. Just about everything in this patent could be taken internally----and that might be a better way to do it. Think about a tablet of finasteride and how it gets to the hair. There would be no way to screw it up. Minoxidil is available in tablet form. You’d only be taking it for about ten days at the very most.

What you’ll be given will be most likely: Finasteride or dutasteride, An EGF-receptor blocker (that probably can start being applied as little as two days post wounding), minoxidil, an anti-histamine, and anti-microbial, and possibly an immunosuppressant. All of these things can be taken internally, once or twice a day at the most.

I hope it works, because frankly I think it will be a snap if it does. I really feel pretty confident about this working in the donor area…but the wounds have to be 2 mm in circumference. It would be interesting to see a guy take some Arava 3 days post transplant for about 7-10 days and see if he regrew hair Gho-like back there in several months time. Could you imagine what this could do for FUE-surgeries when entire follicular units are removed?

Like Ive said…I really hope this works because if Follica or ACELL dont work, its going to be a good five years for virtually certain–and hence we might as well forget about it (I sure as hell will). I hope they get their first little trial started soon. Im anxious, the Example 7 in the patent on human skin, the little stories we occasionally hear of guys regrowing hair on wounded scalps…it feels like the “last hope” as I dont look for anything else to be able to “make” new hair other than HM which seems “out there in the future” at this point.

One last note: That patent is written defensively and intentionally vaugue. They didn’t want it to be too understandable in my opinion. Its super-repeditive and induces sleep to even an insomniac (like me).

3

lol, interesting… I think as chance to success they are respectively: Acell 70% and Follica 30% (for now, obviously, the chance may will change sooner as we can understand)

Follica promise really good things but for now, we knows nothing about that (I mean without trials ongoing on human), perhaps Acell is more close to success cause the wounds are the same thing in human and pets, and their products works damn good on pets, so I really cant imagine why acell shouldn’t works on human

but follica (for now) is different so we cant say nothing more some speculation or imagination

4

There are so many goddam variables in this deal. It concerns me. I hope some of that is just to keep it vague and for experimental purposes.

A multi-chemical cocktail that’s supposed to regrow hair, and it includes the use of both Fin/Dut AND Minox at the same time . . . it sure seems like a recipe to confuse the results.

I think I would have really expected them to do the opposite in fact. I would have expected them to purposely specify that Fin & Dut & Minox & Nizoral all be 100% AWOL from anyone they’re testing their new stuff on. Using all that stuff at once sure seems like a great way to confuse what they’re really having luck with.

And a number of guys like me are NOT very eager to go on Fin/Dut for two weeks unless it’s truly vital to new hair’s formation & survival.

In my case, I can’t tolerate that stuff very well at higher dosages. I take 0.25mg of Fin per day and that’s it. I only tried taking a 0.5mg Finasteride dose one time, and it gave me ball-crushing pain that took days to go away. I don’t even wanna try to imagine what fun it will be if I have to take another full-strength dose of Dutasteride every single morning for two weeks straight. Not gonna be pretty.

If we’re gonna use Fin/Dut for this Follica method, then IMO they had better know for sure that it’s necessary.

5

Has anybody thought about the possibility that the reason Follica are taking so long to get to trial is because they are waiting for Accel to be licensed for use in humans so they can patent it and try it out for hair growth before anyone else lol. They could simplify their process right down, abrade the scalp, apply a pig bladder scaffold for a few days and your set!

Acell doesn’t have much chance of curing MPB in my opinion because nobody is planning on testing it for MPB anytime soon.

6

» I hope it works, because frankly I think it will be a snap if it does. I
» really feel pretty confident about this working in the donor
» area…but the wounds have to be 2 mm in circumference.

Benji, I read somewhere that the wounds would have to be a certain size but I had no idea it was 2mm!!! that is such a small area.

Does that mean say a Norwood class 6 patient would only be able to get a 2mm wound, wait for it to heal and grow hair then repeat, effectively one 2mm wound at a time to cover an NW6 area over a long period of time???
Or could they do multiple 2mm wounds in one sittings do you think???

7

» There are so many goddam variables in this deal. It concerns me. I hope
» some of that is just to keep it vague and for experimental purposes.

I’ve said this before as well, they are adding all possible drugs to the patent to make sure no one else changes the formulation/technique slightly and patents it - a lot of companies do stuff like that.

I’m also sure that we probably need only 1-2 drugs to get maximum hair growth. One thing Costralis himself has been mentioning is the WNT gene, this is the key to new hair growth. The idea being that you damage the scalp and then enable body’s renegeration process to fix it, theoratically giving us our hair back. The only reason I can think of using finasteride before treatment would be to decrease DHT levels in the body like they are in new borns thus providing a favorable environment for hair growth.

8

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9

Man, I really think a lot of you guys are worrying way too much about this wounding process.

They can dermabrade a large area of your head at once.

Maybe they won’t reverse all of a full NW#7’s MPB in one sitting, but we’re not gonna be doing this 30 times just to make one pass over our heads.

10

you guys are talking as if you were sure that it works

11

Science already knows that wounding and then regrowing fresh hair on a MPB’d scalp can work.

It’s just a question of whether Follica has figured out a way to do it or not.

12

The depth of skin disruption can include in increasing amounts:

This is vague. I wonder how deep they are going to go? Full-on dermabrasion is probably too invasive, and simple microdermabrasion is probably not going to wound enough.

As far as chemical peels, phenol (a very deep peel) is also going to be too invasive, while glycolic acid would likely be too mild, IMO (btw, I use high concentration glycolic acid on my face - 70% - and I can’t see that causing enough damage). TCA (a medium peel) is fairly invasive, but it’s a possibility, particularly if used at lower doses. Jessner’s solution may be an attractive option – it’s a chemical peel more powerful than glycolic acid, but weaker than TCA, and it basically induces sunburn-type damage: your skin gets red after treatment, and a couple days later it starts peeling in sheets, which lasts about a week or so – it basically destroys the epidermal layer, which is then regenerated.

13

» Just about everything in this patent could be taken internally

That’s actually what I would prefer.

» It would be interesting to see a guy take some Arava 3 days post
» transplant for about 7-10 days and see if he regrew hair

Yep. Only downwide to oral Arava is that it has a very long half-life in the body. You’d likely still be getting its effects for weeks after you stop taking it (if you take this drug long-term, it can take up to a couple of years for your body to get rid of it all…there are some other meds you can take too speed up its clearance, but even with that, it takes your body 1-2 weeks to get rid of it). I mention this because I am not sure, for hair creation purposes, if EGF receptor antagonism needs to be transient, or whether it can be more long-term.

14

» Yep. Only downwide to oral Arava is that it has a very long half-life

Also, alopecia is a fairly common side-effect of leflunomide, but hopefully short-term use could avoid that, even if it sticks around in the body for a while.

15

» As far as chemical peels

These are also widely available, MUCH cheaper (and less painful!) than dermabrasion, and if you wanted to perform the peel yourself, it’s cheaper than microdermabrasion.

16

I don’t think we would have any incentive to want to mess with long-term EGF receptor meds. The body clearly didn’t originally need it just to keep good hairs after they were first formed in the womb.

The DHT damage from balding shouldn’t be related to the EGF receptor’s processes.

17

TAGOHL,

10 days is the longest the patent says anyone would be on the medications. I think I could handle ten days of an arthritis drug, even if upset stomach is a side effect. I’d prefer to take everything internally for this reason:

"“Optionally, the skin, following the epidermal disruption, is not contacted for a period of time with any substance (e.g., ointment, a bandage, or a device) that is normally administered to an abrasion or wound to prevent infection”, “Here the skin is not contacted with any substance until, for example, the ■ •■ - epidermal disruption -has healed (e.g., any time between 2 days and 3 weeks).”

I really wouldn’t want to risk the propylene glycol or alcohol in the minox, or detergents in shampoo phucking the whole thing up for this crucial three week period. Stem cells building hair follicles in wounded skin can be interrupted by these synthetic chemicals that would act as anti-infectives. The whole point of the body builidng philosebaceous units is so the new hairs can act as skin-regenerative-signalling centers (Pickhart talks about this on his site—how the follicle is the regeneration center in skin). If the body sensed an anti-infective on the scene, who knows how the cellular signalling might be interrupted? None of this probably works without blocking epidermal growth factor, making sure the body cant just go to work making skin. I think getting that blocked is probably the most important part of this patent.

BTW_----------------the stratum cornelium in the skin needs to be at least partially removed. I hate to say it…but one could have four or five beers, take a couple of asprin…and do the wounding part of this with sandpaper or sandpaper affixed to a drill bit or something. The skin is to be pink and shiny, but not bloody…not even a millimeter has to be removed. SUNBURN is mentioned in the patent, and indeed I have read of one person whose opinion I really respect (a medical student named Docj077, who is probably in his residency by now) mentioning strange new hair growth after getting a severe blistering sunburn on his head (hair cut very short). In other words…there wont be any blood in this procedure-there is no need.

Getfitnib is probably the drug they’d use, as you have said…its got a hypertrichotic track record. EGF can be inhibited indirectly by tyrosine kinease inhibitors…but I think they are all prescription. The 2mm width of wound being necessary for the process to happen makes me really think that some FUE transplant patients could get regrowth if they were willing not to wash the back of their head for 3 weeks, use an EGF-receptor blocker, and were on finasteride. Just being on arginine during this time would up Nitric oxide if one could not obtain internal loniten. I think this thing is very doable at home if one can ferret through the patent carefully and get their hands on the necessary ingredients. The simpleist manifestation they mention is merely minox, EGF-blocker, finasteride. Hell, anybody could do that.

18

I hate to say it…but one could have four
» or five beers, take a couple of asprin…and do the wounding part
» of this with sandpaper or sandpaper affixed to a drill bit or something.
» The skin is to be pink and shiny, but not bloody…not even a
» millimeter has to be removed. SUNBURN is
» mentioned in the patent, and indeed I have read of one person whose opinion
» I really respect (a medical student named Docj077, who is probably in his
» residency by now) mentioning strange new hair growth after getting a severe
» blistering sunburn on his head (hair cut very short). In other
» words…there wont be any blood in this procedure-there is
» no need.

Power tools would be an unnessecary risk for just a little test patch. You can do a small area of a couple square cm’s with sandpaper by hand. Start with a meduim-grit and then switch to a finer grit when you’re about halfway down.

We’ve all had scrapes as kids that were a lot worse than this would be. It just takes half a minute of purposely doing it rather than the split-second of pain every time you accidentally fell off your skateboard.

19

but the wounds have to be 2 mm in circumference.

the patent says: between 0-2 millimeteres (mm) in width (e.g., 1 mm, 2 mm, 3 mπij or greater), 0-2 centimeters (cm) in width (e.g., 1 cm, 1.5 cm, and 2.0 cm) or greater

so actually it looks like the size does not matter :slight_smile: between 0-2 mm could also be 0.5 mm. please correct me if I’m wrong

do you know how long I would have to wait to make the cells go in the state where they can be stimulated again because you said I cannot repeat it as often as I want without having a break. that would be interesting for all the people who are needling

20

sandpapering does not hurt at all. you don’t need any alcohol to stand the non-existing the pain :slight_smile: I have done it and it does not hurt. there was even one little hole where blood came out as if i was needling so it was quite deep maybe too deep but it didn’t hurt.

btw. you could even get one pill (250mg) of Gefitnib for $12.50 and make a topical. oh and the wound has to be at least or around 0.5 cm in diameter to form new hair. that is what Chuong is saying in his nature article.