Sunday, March 25, 2012

Vibrating Magnetic Tattoos from Nokia

Nokia has filed a patent application aimed at protecting the concept of vibrating magnetic markings, a news story that has been plastered throughout the media for the past week. Although I'm not surprised at the widespread news coverage for this technology, it is quite interesting that patent applications and patents have very little appeal to the general public until something outrageous like this patent application comes along.

And this concept is outrageous, isn't it? Tattooing magnetic ink, permanently, somewhere on your body, so that you'll never again miss a text message or a call. I can just picture the commercials now. You're at a dance club. The music is deafening. You're in the middle of your signature dance move affectionately referred to as "convulsing" by your closest friends when your tattoo starts to vibrate. Without having your vibrating tattoo, you would've missed that life-or-death text message from your best friend Suzy who's at home right now watching TV - she texts you to say how she absolutely cannot stand that annoying pharmaceutical commercial that constantly repeats the phrase: "like an inhaled corticosteroid." Ugh, I know Suzy's pain.

Nokia filed a provisional patent application for this technology back in September 2010, which means Nokia has been considering this technology at least as early as mid-2010. On September 13, 2011, Nokia filed a nonprovisional application claiming priority to the provisional, and the application was published as U.S. Patent Application Publication 2012/0062371 on March 15, 2012 with the title "Haptic Communication." The application is currently awaiting examination at the USPTO.

At its most basic, the invention comprises a marking on human skin that contains a compound susceptible to a magnetic field, typically a ferromagnetic powder. Upon being exposed to a magnetic field, the magnetic marking moves in some manner (e.g., vibrates) and the person perceives the movement of the marking, thereby communicating some sort of information to the person. The application indicates that the "information" can be a variety of things, such as a "low battery indication, received message, received call, calendar alert, change of profile, e.g. based on timing, change of time zone, or any other."

The magnetic marking can be in a number of forms, including a visible or invisible image, tattoo, marker, sign, label, symbol, or badge. The marking can be applied to the skin in a number of ways, such as stamping, spraying, tattooing, drawing, or attaching an adhesive tape or a decal containing the magnetic marking. In other words, the marking can be permanent or temporary, which makes it ideal for those of us getting frequent MRIs or having an aversion to tattoos (whether they be visible or invisible).

The application was obviously not written by a chemist. Despite the fact that the magnetic ink is arguably one of the most important aspects of this invention, the composition of the magnetic ink is discussed only briefly. For example, the ink is disclosed to be "enriched by ferromagnetic or paramagnetic compounds for example but not limited to iron (Fe), iron oxide (Fe203), magnetite, liquid suspensions of the rare-earth materials for example neodymium (Nd)." The application also discloses that the magnetic ink may be demagnetized by heating before it is attached to a person. Although no reasons are given, presumably demagnetization is suggested because otherwise the ferromagnetic ink would stick to the tattoo needle and make the tattooing process difficult. Of course, heating the ink until demagnetization occurs entails heating above the Curie temperature of the magnet, at which point the alignment of the magnetic domains is destroyed. After application of the demagnetized ink, the marking can be remagnetized by stroking a permanent magnet several times over the marking.

Instead of discussing the magnetic ink, the majority of the application instead discusses other aspects of the invention, such as the form or location of the marking, the device used to create the required magnetic field, or the relationship between the marking and the device. In other words, it appears the Nokia application was probably written by the same patent attorneys at Nokia that probably work on Nokia's more electronic inventions, but are rather unfamiliar with chemistry.

In one of the more interesting embodiments, the application discloses that this technology can be used "for silent communication between an electronic device and a user. Another technical effect of one or more of the example embodiments is to provide a new communication language based on wireless haptics, for example but not limited to set of pulses, frequencies, way of stimuli."

Just imagine if we all learned Morse code - we could get a series of short and long vibrations on our magnetic tattoos, and we'd understand the content of a text message without having to even look at our phones.

Overall, I'd be willing to give this technology a try if it ever makes it to market. Of course, I think I'd first try out a temporary magnetic mark before considering the more permanent tattoo.

The Nokia application contains three independent claims. The claim most representative of the inventive concept is listed below.


The concept of a magnetic tattoo ink is already known, as demonstrated by U.S. Pat Appln Publication 2005/0061198 titled "Magnetic Ink Tissue Markings." It appears, however, that this publication does not disclose the use of the magnetic tattoo as a means to receive some sort of information from an electronic device. Instead, the '198 publication appears to disclose the use of magnetic fields to change or entirely remove a tattoo made with the magnetic ink, also a pretty cool concept.

Sunday, March 18, 2012

Psycho-Spirituality Enhanced Gum

I came across a patent application publication today titled "Chewing Gum Formula For Enhancing Psycho-Spirituality." Yes. That's what it's called. The application is U.S. Patent Application Publication 2011/0038915.

The abstract, in part, is as follows: "The present invention relates to a chewing gum formulation which serves as a means for awakening human consciousness and mindfulness to the sensorial subtleties, which in turn strengthens sovereignty such that overall psycho-spirituality is enhanced."

Wow. I am stunned. I'm not even sure what all of that means. But it means something...to someone...probably.

Apparently the inventor in the application, Eduardo Jose Gonzalez from San Diego CA, found that he could put the botanical plant Salvia divinorum in chewing gum, and he could achieve psycho-spiritual effects. What exactly is psycho-spirituality you might ask? Lucky for us, the application defines it as "the study and practice of the mind's association with metaphysical, moral, and intrapersonal beliefs. It includes the totality of psychic processes, both as conceived by the general rationalistic outward viewpoint of the typical western scientific community, such as Freudian based, Behaviorism, Neuropharmacology, etc., and the more inward oriented spiritual viewpoint more typical of the religions of the east, such as Hinduism, Buddhism, etc."

Again, I am stunned. Without resorting to Google, I can't quite make out what this definition means in its entirety, but I really don't care all that much, since it sounds like a bunch of hooey to me.

What does interest me is the active ingredient in this patent application. As mentioned above, the chewing gum contains the botanical plant Salvia divinorum, and the active ingredient in this plant is salvinorin alpha (i.e., salvinorin A). The structure is depicted below:

Now this is a very interesting natural product. The compound is classified as a trans-neoclerodane diterpenoid, and is the first known compound to act on the kappa opioid receptor that is not an alkaloid (i.e., this compound does not contain any nitrogen atoms, whereas most kappa opioid agonists are alkaloids).

According to the patent application, the low doses of this compound enhances the five senses, "and in moderate to high doses perception becomes extra-sensory." As of August 2009, eleven states in the U.S. have enacted legislation to control Salvia divinorum as a Schedule I drug, though the inventor in this application believes the alleged benefits "far outweigh any of the alleged reasons for enacting such restrictive legislation." The application acknowledges that high doses of the compound tend to "dramatically impair one's motor skills like alcohol but potentially with the added danger of perceptual distortion," i.e., hallucination. However, the chewing gum is allegedly formulated to contain a low to moderate dose, so as to mitigate the acknowledged dangers.

The application states that salvinorin A is "not unanimously considered hallucinogenic," but rather the "proper, nuanced descriptors for salvinorin A" are "oneirogenic" and "phantasticant" since the compound induces "hypnagogia." I'll let you look those words up yourself, but they do sound phantastic don't they?

The inventor believes that, while the compound is among the most potent naturally occurring psychoactive substances, it allegedly is non-toxic and non-habit-forming based upon a survey of the literature conducted by the inventor. 

According to the application, salvinorin A is difficult to administer through ingestion, since the active compound is broken down into an inactive form in the gastrointestinal tract. The application seeks to provide a new delivery method via chewing gum, in which the compound is instead delivered mainly through the mucous membranes of the mouth, i,e., buccally.

When using the chewing gum, the application teaches that "[t]he recommended environment is a quiet, controlled environment indoors, among tranquil music and/or in a non-urban outdoor setting." "Other recommendations are to create a safe space and to plan one's time accordingly since the effect can last two to three hours in moderate and high doses." At last, the application warns that "[w]hen chewing the gum, the individual is recommended to expel the gum from the oral cavity if the experience becomes undesirable," i.e., spit it out if you find yourself seeing pink elephants.

The application contains two independent claims, both method claims, as depicted below.


In order to decrease the absorption of the compound, the user is instructed to employ the "chew and park" technique, in which the user chews once every 3 to 6 seconds, in contrast to the normal consistent chewing technique. However, if the user desires to enhance the absorption of the compound, the user is instructed to, among other things, brush his/her teeth before chewing the gum. Nope, I'm not making this stuff up.

Saturday, March 10, 2012

The CeraVe Patent

Before I started working in the patent field, I used to be impressed by products that claimed to employ some sort of "patented" technology. It made me think that there was something extra special about the product, almost as if the product was more credible or superior to other products because it was patented.

Now that I'm acquainted with the patent field, however, I'm aware that just about anything can be patented, provided that the "thing" is useful, novel, nonobvious, and complies with various other statutory requirements. There is no requirement, however, to prove that the invention actually works as asserted, nor that the product is "better" in any way than other products intended to be used for the same purpose. A patent just means that the Examiner at the US Patent Office took no issue with the asserted utility of the invention, and the Examiner couldn't find any prior art (i.e., references) that disclosed or suggested the claimed invention. Pretty much end of story.

Enter CeraVe®. You must've seen the TV commercials by now for the CeraVe® skin products that claim to be based on a "unique, patented Multivesicular Emulsion (MVE®) delivery technology." When I first saw this, my first impression was "oooh, that sounds cool, it must really work and stuff." Then my brain kicked in and said "hmmm, that marketing campaign must snare lots of customers." I googled CeraVe® and they have a section of their website that gets all scientific about what their products contain, how they work, and mentions their patented MVE® delivery system a few times.

Now, I'm not saying CeraVe® products don't work - in fact they may work exactly as marketed and described on their website - I'm just pointing out that whenever you see a product marketed as "patented," you should be a little skeptical and remind yourself that "patented" does not necessarily mean that the product actually works or is superior to others on the market. CeraVe® just happens to be the most recent chemical case of a product having this type of marketing campaign, and therefore I'm using this situation as an example. (Disclaimer: I have not evaluated the CeraVe® product in any way and cannot speak to the effectiveness of the product).

Quite surprisingly, despite the fact that CeraVe® repeatedly mentions their patented MVE® delivery system on their website and in their commercial, I could not find on their website any reference to the actual patent protecting their invention, even when trying a Google site search. I can only speculate as to the reasons. Luckily, however, there is only one patent I could find assigned to Healthpoint, Ltd. (the owner of the trademark MVE® noted on CeraVe®'s website) that contains the word "multivesicular," and that is U.S. Patent 6,709,663 titled "Multivesicular Emulsion Drug Delivery Systems."

Ok, enough warning you about products marketed as "patented." Let's get into the science of the CeraVe® multivesicular emulsion delivery system! So, what's the gist of the patent? Well, it notes there is a problem with the release rate of most conventional products that are based on regular, single-walled vesicles (i.e., those that are not multi-walled vesicles). Specifically, conventional products, once applied to the skin, allegedly have a "spike" in the release of the active agents contained in the vesicles, which can cause overdosing and skin irritation at the point of application.  In contrast, the MVE® delivery system allegedly has sustained release over a longer period of time, such that overdosing and skin irritation are reduced or eliminated. The patent also notes that the inventive composition affects the biophysical properties of the skin, such as increased blood flow, reduction of transepidermal water loss, and increase of skin hydration.
Multilamellar Vesicle
(source: encapsula.com)

What exactly is a "multivesicular emulsion" anyways? The patent defines it as an emulsion comprising vesicles having a series of concentric spheres or shells of oil and water phases, and states that under a microscope, the vesicles looks very similar to the cross section of an onion. Given this definition, it seems that "multivesicular emulsion" is really just this patent's fancy name for multilamellar emulsions (MLEs) or multilamellar vesicles (MLVs), which are the more generally accepted terms in the field.

The multivesicular emulsion is prepared by mixing an active agent with either water or oil, whichever phase it is most compatible with, and then a quaternary ammonium salt emulsifier is added at a preferred level of 0.5-5 wt.%.  The mixture is then high sheer mixed and the active agent becomes trapped within the concentric walls of the multi-layered vesicles. The resulting emulsion is said to be an oil-in-water emulsion, which makes sense given that the emulsifier is positively charged and thus likely water soluble (or at least more compatible with water than oil).


The active agent can include a variety of compounds, such as those effective against acne, hair growth, canker sores, dry skin, wound treatment, among many others. The emulsifier is a quaternary amine salt derived from colza (rapeseed) oil.  The patent states that the preferred emulsifier is behentrimonium methosulfate (see structure at right), though it lists other salts of behentrimonium to be suitable as well, such as the choride, sulfuate, and ethosulfate salts. The preferred source of behentrimonium methosulfate is the commercial product Incroquat® Behenyl TMS, which comes formulated as a mixture of behentrimonium methosulfate (25%) and cetearyl alcohol (75%), another known emulsifier, which results in cetearyl alcohol turning up in most, if not all, of the formulations listed in the patent.


It appears that the multi-walled structure of the multivesicular emulsion is the cause of the sustained release characteristics of the CeraVe® products. In an example in the patent, the release rate of an anti-fungal drug (econazole nitrate) from the inventive multi-layered vesicles was compared with the release rate of the same anti-fungal drug from the commercial product Spectazole from Johnson & Johnson, which likely is an emulsion of single-walled vesicles. The release rates are compared in the graph to the left. The patent states that "[t]he results of the diffusion test revealed that there was sustained release over a period of time for the multivesicular emulsion of the present invention, but there was a spike release of short duration for the Spectazole." I don't know if I'd characterize the Spectazole trace as a "spike," since the Spectazole trace doesn't start peeling away from the sheet cream trace until about 225 minutes (15 min squared = 3.75 hrs), but clearly the inventive sheer cream does appear to have a lower release rate and thus more sustained release over time.


The patent lists a variety of specific compositions for various products, including a gentle cleanser, sunscreen lotion, ceramide cream, self tanning cream, diaper rash cream, etc.  See the patent at columns 6-7 for all the specific formulations.  I'll focus on the ceramic cream formulation shown on the right, since this seems to be the most relevant to the CeraVe® product featured in the TV commercial.

The Incroquat Behenyl TMS comprises the emulsifier behentrimonium methosulfate that was mentioned above. Cetyl and stearyl alcohols are surfactants, emulsifiers, and/or emulsion stabilizing compounds. Cetiol LC, butylene glycol, and Crodamol OHS are emollients. Germall must be a biocide to prevent bacterial growth. Rovisome ACE is an antioxidant and UV protectant. Ceramide 2 is a skin conditioner. The remaining ingredients, like sesame oil, macadamia nut oil, avocadin, and peach kernal extract are the fancy "natural" ingredients that may have some real world function in the composition, though may also provide merely a psychological effect for the consumer.


Notably, you'll find two ingredients missing from this list in the patent - niacinamide and hyaluronic acid - two of the ingredients featured in the sciency section of CeraVe®'s website. Actually, I can't find either of these ingredients explicitly mentioned anywhere in the patent. Chances are (though I'm just speculating here) that the inventors of MVE® did not envision, at the time of the invention, employing niacinamide and hyaluronic acid in the compositions. Otherwise, they most certainly would have described these ingredients in the patent. At some later date, however, perhaps it was realized that these two ingredients would work well in a moisturizer cream and/or with the MVE® delivery system.

The composition claim (claim 1) in the patent is fairly broad, and minimally requires a multivesicular emulsion consisting essentially of 0.1-30 wt.% of behentrimonium methosulfate and an active agent trapped within the vesicles, in which the emulsion is a two-phase oil-in-water emulsion and has concentric spheres of oil and water.

The "consisting essentially of" transitional phrase has legal meaning in patent law and limits the scope of the claim to the specified materials and those that do not materially affect the basic and novel characteristics of the claimed invention. So, for example, if a potential infringer added a small amount of dye to the composition of claim 1 of this patent, and the presence of the dye did not affect the basic and novel characteristics of the claimed invention, then the potential infringer would infringe the patent. If, however, a potential infringer added a chemical compound to the claimed composition that made the vesicles infinitely stable, such that the active agents remained encapsulated in the vesicles forever after skin application (under normal conditions), then arguably the potential infringer would not be infringing the patent, since the novel characteristic of "sustained release" would not be present.

Saturday, March 3, 2012

The First Aspirin Patent

Aspirin, formally known as acetylsalicylic acid, is one of those staple go-to drugs found in virtually everyone's medicine cabinet. It helps ease our aches and pains (analgesic), and can even reduce fevers (antipyretic). Believe it or not, aspirin has a long and fascinating history dating back to at least as early as 400 BC, where derivatives of the drug (found in willow and other types of plants) were used to treat various ailments. It was not until the 1800s, however, that aspirin was first synthesized in a laboratory.

In the early 1800s, a chemical compound known as salicin was first isolated from willow bark. Salicin is a close structural analogue to aspirin and is converted into a precursor (salicylic acid) to aspirin upon being metabolized in the body. The reaction scheme is shown below. In reality the hydrolysis and oxidation steps may be reversed, but the below scheme summarizes the gist of the reaction.


Purified salicin and salicylic acid started to be used in the late 1800s as pain relievers, but a significant drawback was that these compounds were severely irritating to the stomach. It was eventually found that if salicylic acid was acetylated, the resulting compound (aspirin - i.e., acetylsalicylic acid) was much more tolerable to the stomach, and thus the miracle drug aspirin was born.

Aspirin appears to have been first synthesized by Charles Frederic Gerhardt in 1853, but Gerhardt apparently did not market the compound, nor use it in any way as a medical treatment. However, in 1897, a German chemist working for Bayer named Felix Hoffmann synthesized aspirin in a Bayer laboratory and recognized its potential as an analgesic/antipyretic drug. Aspirin was the name for the drug originally coined by Bayer, and was actually trademarked at some point, but Bayer eventually lost the rights to the Aspirin trademark for various reasons. This loss of rights to the trademarked name is the reason why you can go out to the store today and find the name "aspirin" on every bottle of the drug, including generics.

Dr. Felix Hoffmann filed a U.S. patent application directed to acetylsalicylic acid (aspirin) on August 1, 1898, and the patent issued on February 27, 1900 as U.S. Patent 644,077. Interestingly, aspirin was ineligible for patent protection in Germany, and a patent was briefly granted in Britain before being overturned a few years later. Perhaps the fact that that the compound was known from Gerhardt in 1853 and Kraut et al. in 1869 (see below) was the reason these European countries would not allow aspirin to be patented.

Hoffmann's U.S. patent claims aspirin itself, i.e., the article of manufacture, instead of any method of making or use thereof. The claim is as follows:


The U.S. patent application is one of the more unusual ones I have ever seen, though I suppose I have not read many patent applications from around 1900. The application is one page, and the majority of the text discusses the reasons why a previously published journal article by Kraut et al. that claims to have synthesized acetylsalicylic acid did not in fact synthesize the compound.

Specifically, Hoffmann's patent application discloses: "In the Annalen der Chemie und Pharmacie Vol. 150, pages 11 and 12, Kraut has described that he obtained by the action of acetyl chlorid on salicylic acid a body which he thought to be acetyl salicylic acid. I have now found that on heating salicylic acid with acetic anhydride a body is obtained the properties of which are perfectly different from those of the body described by Kraut. According to my researches the body obtained by means of my new process is undoubtedly the real acetyl salicylic acid [see structure above]. Therefore the compound described by Kraut cannot be the real acetyl salicylic acid, but is another compound. In the following I point out specifically the principal differences between my new compound and the body described by Kraut." In other words, both Kraut et al. and Hoffmann employed salicylic acid as a starting reactant, but Kraut employed acetyl chloride as the acetylating reagent, whereas Hoffmann employed acetic anhydride.

Hoffmann proceeded to discuss the results of various tests he performed on his own acetylsalicylic acid compared to the results of the same tests reported in the journal article by Kraut et al. The results of these chemical tests suggest that Kraut et al.'s product was mainly salicylic acid (without explicitly stating as much), whereas Hoffmann's product was the acetylated version of salicylic acid, i.e., acetylsalicylic acid (aspirin). Given the facts set forth in two court decisions (discussed below), it is likely that Kraut et al. had actually produced a mixture of salicylic acid and aspirin, perhaps weighted more towards salicylic acid.

In the Hoffmann patent, it is noted that Kraut et al. reports that boiling their product in water, even after a long period of time, does not produce acetic acid, whereas Hoffmann states that his product does produce acetic acid upon boiling in water. Of course, in this test the acetyl group in Hoffmann's aspirin hydrolyzes to form salicylic acid and acetic acid, whereas Kraut's compound apparently does not have an acetyl group. Next, Hoffmann reports that mixing Kraut et al.'s product in an aqueous solution of ferric chloride results in a violet color (a well-known test for the presence of phenols), whereas Hoffman asserts that an aqueous solution of his product with ferric chloride does not turn violet. Salicylic acid has a free phenol, whereas aspirin does not (it is acetylated), such that the results of the ferric chloride test are reasonable. Last, Hoffmann notes that Kraut's "body" solidifies at around 118 C upon cooling from a melted state, whereas Hoffmann's product solidifies at a much lower temperature of 70 C. Hoffmann concludes that "[i]t follows from these details that the two compounds are absolutely different." Since NMR and mass spectrometry had not yet been invented in 1900 (or at least not yet in use as the analytic tool we know and rely on today), the foregoing tests described in the Hoffmann patent were all he could really rely on.

The Hoffmann patent has a litigious history. Around 1909, the patent owner Farbenfabriken of Elberfeld Co. (a precursor company of Bayer) sued Edward Küehmsted in District Court for infringing the aspirin patent. Küehmsted contended that aspirin was a known compound that was disclosed in Kraut et al., and thus the aspirin patent was anticipated by Kraut et al. and therefore invalid. In a decision that was issued on August 11, 1909 (171 F. 887), the District Court upheld the validity of the aspirin patent, found that Küehmsted infringed the patent, and issued an injunction against Küehmsted. Küehmsted appealed to the Seventh Circuit Court of Appeals in 1910. Interestingly, the District Court's decision references the events pertaining to an English patent on aspirin:
An English patent on the Hoffman invention was taken out by one Newton December 22, 1898. In 1905 an infringement suit was heard in the Chancery Division of the High Court of Justice before Mr. Justice Joyce, and resulted in the patent being declared void for anticipation. From the evidence in that case the court found that:

"The crystalline mass is substantially acetyl salicylic acid. Almost the whole of it is the compound acetyl salicylic acid completely formed. For practical purposes the whole may be taken to be and be used as acetyl salicylic acid. Its general and therapeutical characteristics are the same those of pure salicylic acid."
The District Court, however, found that the facts of the English patent differed from those of the U.S. case, and even if the facts were the same, the differences between the patent laws of the U.S. and England precluded attributing any authority to the English court's decision.

Upon appeal in the U.S., the Seventh Circuit affirmed the decision by the District Court. The Seventh Circuit's decision (179 F. 701) issued May 11, 1910 contained two concurring opinions from Circuit Judges Grosscup and Kohlsaat (apparently the third judge on the panel, Baker, dissented). The court's decision is an interesting read and essentially held that Hoffmann's pure form of aspirin is useful as a therapeutic agent, whereas Kraut et al. likely produced an impure form of aspirin that could not be used as a therapeutic agent. Thus, Hoffman's pure aspirin is patentable over the aspirin gemisch reported by Kraut et al. A fitting soundbite from the decision is as follows:
Hoffmann has produced a medicine indisputably beneficial to mankind - something new in a useful art, such as our patent policy was intended to promote. Kraut and his contemporaries, on the other hand, had produced only, at best, a chemical compound in an impure state. And it makes no difference, so far as patentability is concerned, that the medicine thus produced is lifted out of a mass that contained, chemically, the compound; for, though the difference between Hoffmann and Kraut be one of purification only - strictly marking the line, however, where the one is therapeutically available and the others were therapeutically unavailable - patentability would follow. In the one case the mass is made to yield something to the useful arts; in the other case what is yielded is chiefly interesting as a fact in chemical learning.
It appears the Seventh Circuit's decision on the patentability of a pure compound over an impure compound was nowhere near the first of its kind, at least in view of the various other court decisions cited as support in both the Seventh Circuit's and the District Court's opinions in this case. Even today, a pure product can be patentable over a prior art impure product, provided that the pure product is unobvious (see M.P.E.P. 2144.04 (VII)).

Aspirin has been the subject of many patents over the years since Hoffmann's first aspirin patent. A brief Google Patent search for aspirin (or variations thereof) in the titles of issued patents and patent application publications turns up around 3,300 hits (not a perfect measure, but it'll suffice). Many of these applications appear to be directed to increasing the stability of aspirin, creating an aspirin pill with desirable release characteristics (e.g., sustained release), and/or an improved production method.

One of the most recent issued patents directed to aspirin (US 8,017,368, issued September 13, 2011) claims a method of permeabilizing a cell membrane with aspirin in order to allow molecules not normally able to cross a cell membrane to make it across. Apparently after the cell membrane has been permeabilized with aspirin, the integrity of the membrane is regained. The examples demonstrate the success of this method using the fluorescent molecule calcein (easy to track in the experiments), but the patent notes that this method could work with other species, such as elements, charged species/compounds, chemicals, drugs, proteins, and nucleic acids.

Sunday, January 15, 2012

The Chemistry of Magnetic Nail Polish



blog.flauntme.com
The other day I was reading See Arr Oh's excellent "Just Like Cooking" blog and came across a post on magnetic nail polish.  In essence, you apply the magnetic nail polish to your nail, hover a magnet over the still wet nail, and a pattern will be created in relation to the magnetic field lines of the magnet. Since I typically don't paint my nails (except for special occasions :-) ), I had never heard of such a thing, but it sounded like an interesting and novel product that likely would be patented, or at least patent pending.

Sure enough, after a brief search I found a family of seven pending US patent applications (see list at the bottom of this post) directed to magnetic cosmetic compositions.  The pending applications are all assigned to L'Oreal, which is the parent company of Lancome.  Notably, Lancome appears to be the first company that marketed magnetic nail polish under the brand name Le Magnetique in 2007.

Although many different companies have marketed magnetic compositions since 2007, including Sephora and LCN (as pointed out in See Arr Oh's post), it appears that Lancome's Le Magnetique started the trend, and indeed, L'Oreal has sought patent protection for this technology at least as early as October of 2004.

The beauty of patents (and patent applications) is that they fully disclose, albeit in a somewhat confusing manner sometimes, a commercial technology that otherwise would be a mystery in a variety of respects.  Just think of Coca-Cola.  Although every can of Coke has an ingredient list on the back, the taste of Coke arguably has never been duplicated, since important details regarding the ingredients are missing, such as the ingredient proportions, processing conditions, and the source of ingredients.

In the present case, while the various ingredients contained in a magnetic nail polish are disclosed to consumers, there are important details missing that cannot be determined from an ingredient list alone.  However, if we look to the patent applications directed to this type of technology, the purpose of each component is typically explained, we find example compositions detailing the exact proportions of ingredients, and we are provided with an expanded view of the potential scope of this technology, for example, the identities of the various dyes that can be used, the physical structure of the magnetic particles, and the potential use of these magnetic compositions in cosmetics other than nail polish.

Of course, the compositions disclosed in these patent applications are only representative, and it is highly likely that the magnetic compositions have been changed/optimized prior to L'Oreal bringing the products to market.

With all of this in mind, we come to our question of the day...what's the chemistry of magnetic nail polish as taught by L'Oreal's patent applications?

The magnetic particles are not necessarily just iron powder tossed into the composition, but rather there is a lot of detail regarding the magnetic particles that is not readily apparent from the ingredient list.

For example, the magnetic particles can be made of any material that can be moved under the effect of a magnetic field, which includes nickel, cobalt, iron, and rare earth metals, such as gadolinium, terbium, dysprosium, and erbium.  The metals can be employed in any state that has a magnetic susceptibility, including as an alloy or an oxide.  The most preferable type of magnetic particle appears to be magnetite, i.e., Fe3O4 or iron(II,III) oxide.

The magnetic particles preferably are aspherical, i.e., non-symmetrical, such that the longitudinal axis can be aligned by a magnetic field, thereby changing the appearance of the composition.  For example, the application of a magnetic field to oblong-shaped magnetic particles will orient the particles in one direction, likely causing the composition to have a visible pattern.  In one embodiment, the magnetic particles can be employed in the composition as a ferrofluid, i.e., a stable colloidal suspension of magnetic nanoparticles.

The magnetic particles can also be employed in the composition as organic/inorganic composite fibers.  For example, the magnetic particles, such as Fe3O4, can be dispersed on the surface of a polymeric fiber, or the particles can be embedded therein to form a matrix.  The composite fiber optionally can be coated with a clear or colored membrane, so as to provide a colored composite fiber and/or to provide a barrier between the fiber and the external environment.  In another embodiment, chains of covalently-linked polystyrene particles embedded with iron oxide can also be used.

By employing composite fibers or polymeric particle chains in this manner, it appears that the magnetic particles may collectively "drag" the fibers along under the influence of a magnetic field, as opposed to simply moving the magnetic particles individually.

The patent applications also describe a variety of dyes/coloring agents that can be employed in the magnetic compositions, including goniochromatic, photochromic, thermochromic, and/or piezochromic (in particular tribochromic and solvatochromic) coloring agents.  These are just fancy words that mean the color of the composition can appear to change based on viewing angle (e.g., in the case of diffractive pigments and nacres - think pearls), or the composition will actually change change color in response to an applied external stimulus, such as ultraviolet light, temperature, or pressure.

Reflective particles (similar to glitter) can also be included in the magnetic composition.  The reflective particles can be made of inorganic substrates, such as silica or alumina, which are coated with a metal or metallic material, such as silver or a nickel/chromium/molybdenum alloy.

The magnetic nail polish composition preferably includes volatile organic solvents, such as alcohols (e.g., ethanol or isopropanol), glycols (e.g., ethylene glycol or glycerol), and short-chain esters (e.g., ethyl acetate).  The purpose of the volatile organic solvent is to make the composition fluid for a short period of time after application, such that the magnetic particles can easily move under the influence of an applied magnetic field.  Upon drying, however, the magnetic particles will be locked into place in the dried composition, thereby setting the pattern that has been created.

To aid the composition in "locking down" the magnetic particles and the other various components of the composition, a film-forming polymer typically is included.  Examples of film-forming polymers include nitrocelluose and polycondensates.  Polycondensates are polymers formed by a polycondensation reaction and include copolymers of adipic acid, neopentyl glycol, and trimellitic anhydride.

Various other components can be included in the magnetic composition, such as thickeners (e.g., clays), and plasticizers (e.g., arylsulfonamides), but these are standard components included in most types of cosmetics, and thus are not very interesting for the purposes of this post.

A typical magnetic nail polish composition is as follows:

Nitrocellulose (11 wt.%)
N-ethyl-o,p-toluenesulfonamide (5 wt.%)
Alkyd resin (10 wt.%)
Isopropanol (4 wt.%)
Magnetic pigment (0.5 wt.%)
Butyl acetate / ethyl acetate 50/50 mix (balance)

The magnetic pigment in this example is Colorona Patina Gold sold by EMD Chemicals, which is described as a dark golden lustrous powder composed of mica, TiO2, Fe2O3, and Fe3O4.

The magnetic compositions are not limited only to nail polish in these patent applications, but variants of the compositions can be applied to any keratinous substrate, such as skin, lips, and hair.  One specific application noted is the use of magnetic compositions in foundation makeup (see Figure at right).  For example, after the magnetic foundation is applied, any sharp transitions between light and dark colors can be smoothed with a magnet so as to blend and soften the edges/transitions of the makeup.

I could go on and on about the magnetic compositions disclosed in these patent applications, since they really are quite fascinating, but if you're interested in more details about this technology, please read the patent applications listed below.

It appears the US Patent Office is close to granting these patent applications (as judged by the prosecution history on PAIR), and if that's the case, we won't be seeing any competitors products sold in the US anymore, unless they are licensed by L'Oreal (or if the competitors happen to design around the patent claims or think the patent claims are invalid for some reason).

Here are all of the pending US patent applications relating to magnetic cosmetic compositions assigned to L'Oreal:

US 2006/0088484 (more general disclosure of compositions comprising magnetic particles)
US 2008/0044443 (magnetic compositions comprising dyes that absorb visible light)
US 2008/0050324 (magnetic compositions comprising diffractive pigments)
US 2008/0105272 (magnetic compositions comprising interferential pigments)
US 2008/0124288 (magnetic compositions comprising coloring agents sensitive to an external stimulus)
US 2008/0127990 (magnetic compositions comprising reflective particles)
US 2009/0130037 (magnetic compositions comprising a volatile solvent)

Monday, January 2, 2012

Silica-Based Sensors (US Patent 8,084,001)

U.S. Patent 8,084,001 (Burns et al.) issued December 27, 2011 and is titled "Photoluminescent Silica-Based Sensors and Methods of Use."  Burns et al. is assigned to the Cornell Research Foundation in Ithaca, NY.

Photoluminescent-based assays are highly desirable in sensing applications as a result of their excellent contrast, high specificity, and fast response times.  The workhorses of these systems are photoluminescent dyes that are sensitive to changes in their environment.  Typically these dyes have been employed in a variety of sensing platforms, including free in solution, thin films, membranes, and optical fibers.  However, many of these platforms can affect the responsiveness of these dyes, e.g., their ability to respond to environmental conditions or analytes.  In view of these drawbacks, Burns et al. seeks to provide a sensing system that can operate in a variety of environments.

Burns et al. discloses silica-based sensors comprising a reference dye and a sensor dye.  The emission spectrum of the reference dye is substantially insensitive to environmental conditions and/or analytes, whereas the emission spectrum of the sensor dye has a known response to a given external condition and/or analyte.  Thus, the reference dye serves as an internal standard to which the response of the sensor dye can be compared, much the same way that the residual solvent peak in proton NMR serves as an internal standard to which the proton resonances of an analyte are compared.

The silica-based sensors can have various structural configurations, but typically comprises a silica core surrounded by one or more outer shells.  The outermost shell typically contains the sensor dye to allow interaction with the external environment, whereas the reference dye is typically included in the silica core or an intermediate shell to prevent the reference dye from contacting the environment.

The periphery of the silica can be tailored to allow targeted interactions to take place.  For example, the silica can be functionalized with amino groups thereby imparting a positive charge to the periphery of the silica, which promotes adhesion of the amino-functionalized silica to cell surfaces.  Alternatively, the silica surface can be functionalized with hydrophobic groups, which allows the silica to intercalate within the lipid bilayer of a cell wall, for example.

The sensor dyes can be sensitive/responsive to a wide range of external stimuli, such as hydrophobicity/hydrophilicity, presence or absence of metal ions, changes in pH, or identification of small molecules such as oxygen.

One specific disclosed potential application is in vivo or in vitro determination of the redox state of a cell.  It is well-known that the internal cell environment is typically a highly regulated reducing environment.  Any deviation from this reducing state could indicate the presence of a disease, such as cancer, or an injury, such as stroke.

Sensing environmental conditions and/or analytes is typically performed by (1) comparing the emission intensity ratios of the reference and sensor dyes, (2) comparing spectral shifts of the reference and sensor dyes (i.e., the difference between lambda maxes), and/or (3) comparing the excited state lifetimes of the reference and sensor dyes.  Of course, the emissions of these dyes in various environments must be previously known via the construction of a calibration curve in order to be able to identify a certain condition or analyte in an unknown solution/medium.

The sole example in Burns et al. demonstrates the determination of the pH of an unknown sample.  A silica-based sensor is first synthesized by covalently attaching a tetramethylrhodamine reference dye to a silica core, followed by layering over this core a shell comprised of a fluorescein sensor dye covalently bonded to silica.  A calibration curve is then determined for this sensor by measuring the ratio of the reference and sensor dye emission intensities over a pH range of 5-9.  Thus, when this sensor is added to a solution having an unknown pH, the ratio of emission intensities of the reference and sensor dyes can be measured and compared with the calibration curve, thereby determining the pH of the solution.

Burns et al. only contains product claims.  Claim 1 is very broad and minimally requires (1) a reference dye and a sensor dye that are chemically different, (2) at least one of these dyes is covalently attached to a silica core, (3) the reference dye has a relatively constant emission in different environments, and (4) the sensor dye exhibits different emission in different environments or in the presence of varying concentrations of analytes.

As filed, the application originally also contained method claims that were restricted out and ultimately canceled in response to the restriction requirement.  Two methods were claimed:  (I) a method of determining an analyte in an unknown environment, and (II) a method of introducing a silica-based particle into an organism.  Perhaps these method claims will appear in a divisional application at some point in the future, though no related applications are currently listed in PAIR.

Sunday, November 27, 2011

Patent Bar Exam to be Updated January 2012

On November 23, 2011, the USPTO announced that the Patent Bar Exam will be updated to cover two new rules related to provisions of the America Invents Act (AIA), and one new rule effected by the USPTO (and not related to the AIA).  The changes to the examination content are expected to go into effect on or about January 31, 2012.

The new material includes (a) the implementation of a prioritized examination procedure (per AIA), (b) revision of the standard for granting an inter partes examination request (per AIA), and (c) rules governing ex parte appeals before the Board of Patent Appeals and Interferences (BPAI) (per USPTO), discussed in more detail below.

(a) The prioritized examination procedure is the first track (Track I) of a three track system designed to streamline the patent examination process and to give Applicants greater control over the examination timeline of their applications.  Information on this procedure was published in the Federal Register and can be found here.  The prioritized examination procedure became effective as of September 26, 2011 and can be requested by any Applicant filing an original utility or plant application.

(b) The inter partes reexamination procedure will be replaced by a new inter partes review process as of September 16, 2012, in accordance with the provisions of the AIA.  The AIA also provides that any inter partes reexamination request filed between September 16, 2011 and September 16, 2012 will only be granted if there is a reasonable likelihood that the requester will prevail with respect to at least one claim challenged in the request.  The previous standard for granting an inter partes examination request required a substantial new question of patentability with respect to any challenged claim.  Information on the inter partes reexamination/review procedure was published in the Federal Register and can be found here.

(c) The USPTO has amended various aspects of the rules governing appeals before the BPAI, including (i) removing several of the briefing requirements typically required for an appeal brief, (ii) providing for the Board to assume earlier jurisdiction over the appeal, (iii) no longer requiring Examiners to acknowledge receipt of reply briefs, (iv) creating procedures for appellant to seek review of an undesignated new ground of rejection issued either in an Examiner’s answer or in a Board decision, (v) providing that the Board will presume that the appeal is taken from all claim rejections unless the claims are cancelled by an applicant’s amendment, and (vi) clarifying that, for purposes of the Examiner’s answer, any rejection relying on evidence not present in the Office Action from which the appeal is taken shall be designated as a new ground of rejection.  These new rules are applicable to all appeals stemming from notices of appeal filed on or after January 23, 2012.  Information on these new rules was published in the Federal Register and can be found here.

Earlier this year (in April), the USPTO updated the Patent Bar Exam for the first time in about five year to test material contained in the MPEP Edition 8, Revision 8 (previously Ed. 8, Rev. 4 was tested), as well as to include material in the exam relating to (1) developments in the obviousness inquiry after KSR Int'l Co. v. Teleflex Inc., (2) new interim patent subject matter eligibility examination instructions, (3) interim guidance for determining subject matter eligibility for process claims in view of Bilski v. Kappos, and (4) supplementary examination guidelines related to § 112 requirements.

While not all aspiring patent attorneys or agents will be very enthusiastic about these updates, simply because the precise nature of the new questions is unknown (there are no practice questions yet available), one thing is certain:  these updates to the Patent Bar Exam will be good for the overall patent community, including the USPTO, practitioners, and applicants, since these exam updates ensure that newly registered patent attorneys and agents will possess an up-to-date knowledge of the laws, rules, and procedures required to practice before the USPTO.