Month: February 2014

Drugs, Microbes, and 35 U.S.C. § 101, Oh my!

Drugs. What is a drug? Any chemical that alters a functional living system is a drug. However, a drug in itself does not have an effect without binding to a receptor. Receptors are macromolecular components found in the cell membrane. Drugs typically bind to receptors through chemical bonds such ionic bonds, covalent bonds (strong), Van der Waals forces (weak), and hydrophilic or lipophilic interactions. Why does any of this matter? The nature of the bond between the drug and the receptor is that drug’s affinity and affinity is one of the two most important qualities of an agonist (a drug that binds to a receptor). The other most important quality is efficacy. Efficacy is the agonist’s ability to activate the receptor and “effect” the living system, producing a response.

An example is caffeine. Caffeine binds to adenosine receptors and acts as antagonist (competes with adenosine and prevents the substance from binding). When adenosine is inhibited I feel more wakeful, for a longer amount of time.The caffeine has altered my system. Although this is the basis of what I got out of Vertebrate Neurobiology class in college my short lesson in Pharmacology unexpectedly answered my question to patents and microbes.

It seems like a frivolous question with an obvious answer but what IS the difference between a drug and a microbe? Microbes can bind to receptors and alter a living system like drugs can. However, microbes are not chemicals. A chemical is defined as “a compound or substance that has been purified or prepared, especially artificially.”  Purify is defined as the removal of contaminants. A contaminant pollutes or adulterates the substance. Is this just semantics? No. This analysis slowly creeps to the heart of why there are so many drugs that are patented day after day and why seeking to patent a microbe could lead to years of litigation. Drugs are a deliberate composition of substances that are for the most part, artificially made. This is why Penicillin could no longer be patented. It was not artificially made, it is derived from mold.

If something is artificial, it is man-made and not made from nature. So where do we draw the line? For example you cannot patent a microbe found in nature but you can patent the process of purifying the microbe like you could patent a purified chemical substance.  35 U.S.C. § 101, provision 43 “Product of nature,” (citing In re Ridgeway). According to the § 101 it is all about process, newness, and usefulness. You have a microbial invention? You want to patent it? Show the court that your invention has a unique process that is not of nature but applies nature in some essence. Show the court that your invention is new and useful. Then you have reached patentable territory because in so many ways your microbe has become a drug.  

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Bacterial Inventions

More ways inventions involving bacteria are used today. Here are some articles about it:

1. Bacteria are being used to make sunscreen more effective

http://www.ideaconnection.com/new-inventions/bacteria-could-boost-sunscreen-07376.html

2. Bacteria are now powering light bulbs. The invention is known as a “Biobulb.”

http://www.ideaconnection.com/new-inventions/biobulb-shows-bacteria-in-a-new-light-07388.html

3. Scientists create rechargeable bacteria batteries

https://www.sciencenews.org/article/bacterial-batteries-get-solid-boost

 

Curing Thrush with Patented Probiotics?

Scientists in Italy have used two strains of lactobacilli to fight vaginal thrush. Thrush is a fungal infection caused by Candida albicans, a usually harmless fungus in the vaginal microflora. The  interesting thing about this experiment is that these scientists were able to patent the two lactobacilli strains, Lactobacillus rhamnosus IMC 501® and Lactobacillus paracasei IMC 502®, also known as SYNBIO®. How can we reconcile this with the Supreme Court’s Decision in Diamond v. Chakrabarty and Funk Bros. Seed Co. Kalo Inoculant Co.

For the full article:

http://www.medicalnewstoday.com/releases/272869.php

 http://www.sciencedaily.com/releases/2014/02/140219075721.htm

A U.S. Supreme Court decision could affect the patentability of viruses

The most recent case that U.S. Supreme Court decided regarding patenting things derived from nature is Ass’n for Molecular Pathology v. Myriad Genetics Inc. The controversy in this case was whether DNA and cDNA could be patented.

DNA (deoxyribonucleic acids) makes up the genetic code of organisms. “Genes” are basically sequences of phosphorylated sugars connected by hydrogen bonds. These phosphorylated sugars are called “nucleotides.” There are four nucleotides in DNA: thymine, adenine, guanine, and cytosine.

In Ass’n for Molecular Pathology, Myriad found two genes that cause breast and ovarian cancer, BRCA1 and BRCA2. Ass’n for Molecular Pathology v. Myriad Genetics,  Inc., 133 S. Ct. 2107, 2111  (2013). After finding the precise location and genetic sequences of the genes, Myriad sought to patent its discovery.  The Court addressed two issues. Id. 1. Whether a DNA segment found in nature is patentable based on its location, and 2. whether “synthetic” DNA, known as complementary DNA (“cDNA”) is patentable. Id. The Court held that DNA is a product of nature and is therefore not patentable but cDNA does not naturally occur and is patentable. Id. The Court also found that mere isolation of genetic material is insufficient to warrant patentability. Id at 2120. During the analysis, Justice Thomas cited 35 USC § 101, and Diamond v. Chakrabarty (among other cases) to support the Court’s decision. (The Court’s opinion in the case will be discussed in further detail in later posts in the context of bacterial patenting.)

So what does this have to do with viruses?

Well viruses are basically “bags” of DNA or RNA. David Baltimore, a renowned virologist, divided viruses into four categories based on genetic material. Viruses either have single-stranded RNA (“ssRNA”), double-stranded RNA (“dsRNA”), single-stranded DNA (“ssDNA”) or double-stranded DNA (“dsDNA”). This is known as the “Baltimore classification.” Baltimore also divided the viruses even further by method of replication.

Viruses are generally not considered living things, but they are found in nature. Hypothetically speaking, if a scientist sought to patent a virus that could benefit the world in some way I believe the Ass’n for Molecular Pathology case could affect whether or not the virus was patent eligible because the case rules on patenting genetic material. However, the extent to which the case would affect virus patentability would depend on the facts.

I believe that patenting entities that derive from nature is not merely determined by a bright line rule. On the contrary, the Court takes an ample amount of time discussing the facts of each case before ruling on patentability. Arguably, the controversy could be settled with one question: is this “thing” a part of nature or not? However, Justice Thomas in his opinion cites the Court in Mayo Collaborative Servs. v. Prometheus Labs, stating that ” [t]he rule against patents on naturally occurring things is not without limits, however, for ‘all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas’ and ‘too broad an interpretation of this exclusionary principle could eviscerate patent law.'” This means that the rule does not exclude all things derived from nature. To do so would impair discovery and inventions. So perhaps the Court uses a rule of reason instead?

 

Chemist’s Patent may change Microbiology Forever

After stating the benefits of having bacteria around, it would seem rather hypocritical to post about antibiotic resistance. Well, I have no choice really. The fact is that one of the most incredible inventions was patented yesterday. A chemist has created a drug that can make bacteria that are resistant to multiple drugs, susceptible to antibiotics again.

Why is this so amazing? Well during the dawn of new and emerging antibiotics the world believed that there wasn’t anything we couldn’t cure. Gonorrhea? Antibiotic. Tuberculosis? Antibiotic. Urinary Tract Infection? Antibiotic. Antibiotic. Antibiotic. Companies were even creating toys with inherent antimicrobial activity.

The prevalence of pathogenic bacteria was supposed to be a thing of the past. However, sedated by triumph the human race began to “over-do” the use of antibiotics (antimicrobials in general) to the point where several strains of bacteria could no longer be killed by that particular antibiotic. “Resistance” ensued. It turns out that when bacteria are killed off, a very small percentage that have acquired mutations randomly during proliferation can survive. The percentage that survive eventually replicate creating a new “quasi-species” of bacteria.These bacteria were a doctor’s worst nightmare. Especially when the bacteria acquired resistance to more than one drug.

However, thanks to Jørn Bolstad Christensen we may have hope in prolonging the usefulness of antibiotics in medicine. Of course he patented a drug (not bacterium) so the analysis differs from the analysis in Diamond v. Chakrabarty.

For full article:

University of Copenhagen – Faculty of Science. “Chemist gets U.S. patent for solution to antibiotic resistance problem.” ScienceDaily. ScienceDaily, 17 February 2014. <www.sciencedaily.com/releases/2014/02/140217085244.htm>.

Bacteria giveth and taketh away

Bacteria usually get a “bad rep.” Admittedly as a microbiologist, you’re taught more about how to kill bacteria than how to use them for the betterment of humankind. However, the truth is that bacteria aren’t going anywhere. Why should they be eradicated? They were here before us, they’re apart of us now, and they’ll probably be here when the human race is no more.

Yet, old habits die hard. The truth is that the average person is more concerned with the 99% antiseptic activity in their “Purell” hand sanitizer, than about how the microflora in their gut helps them digest food and absorb nutrients. Although it is true that pathogenic bacteria can be absolutely devastating, generalized “bacteria-phobia” is probably why the field of patenting genetically modified, new and useful bacteria is so untouched.

Well I’ve decided to dedicate today’s posting to a list of three ways bacteria may help or is helping humanity:

1. Scientist have found a bacterium from the deep sea that has the ability to fight human tumors

Check it out at: http://www.nature.com/ja/journal/vaop/ncurrent/full/ja20143a.html

2. Bacteria placed in a non-toxic liquid crystal may help physicians detect diseases sooner

Article: http://www.sciencedaily.com/releases/2014/02/140217200749.htm

3. Bacteria help create synthetic insulin, which helps patients with diabetes

http://www.dnalc.org/view/15928-How-insulin-is-made-using-bacteria.html

The truth is, bacteria do a whole lot more. With all of these advances taking place it is only a matter of time before “bacteria” and “patents” become frequent bedfellows, changing the world one discovery at a time.

Bacterial Spores can lift cars?

First, I’d like to thank you for visiting my blog. Trying to become a specialist in two vastly different areas is a very daunting and intimidating task. However, I have such a passion for microbiology and the law both. My passion is what drives me and I hope to learn more and become a better scientist and a better (future) attorney.

Now…

Scientific Background:

A spore is like a shield, it protects the bacterium. When times get “tough” in the bacterial world a bacterium may form a spore. These tough times may be the result of a shortage in nutrients in the environment or harsh environmental conditions (too dry, too salty, too uncomfortable to grow). The spore allows the bacterium to essentially “hibernate.” In fact, the bacterium experiences very low metabolic activities and enjoys the shade of the nice hard, keratin shell it has surrounded itself in. Unfortunately, not all bacteria can form spores. Spore formation is reserved for gram positive bacteria because gram positive bacteria have a thick peptidoglycan wall, but gram negative bacteria do not have a thick wall. Basically, gram negative bacteria just don’t have what it takes! (Don’t worry, gram negative bacteria have their own tricks.)

So…

As I leisurely browsed Science Daily, I found a very interesting article, “Electrical generator uses bacterial spores to harness power of evaporating water.” The first thing I thought to myself of course is, “I wonder if this is patentable?” The next thing I thought was “[h]ow does this work?” Let’s start with how it works.

How it works (a very simplified version):

According to scientist Dr. Ozgur Sahin, associate professor of biological sciences and physics at Columbia University, water evaporation is the largest source of power found in nature.* Essentially, Dr. Sahin and a team of other scientists are trying to use nature’s #1 power source to generate electricity.* No one has ever done this before. However, these scientists believe that they can usher in an era of renewable energy with the help of Bacillus subtilis, a spore-forming gram positive bacterium typically found in soil.

The experiments showed that when moisture levels varied, the spores shrank or expanded in response to the varying levels.* According to the article in Science Daily, the response was so dramatic that exposing a pound of spores to intense dryness followed by moisture created enough energy to lift a car!* Apparently this is due to a “humidity-driven force” that has more force than our muscles.*

The scientists are now contemplating genetically altering spores so that the altered spores can harness twice as much energy as the unaltered spores.* This discovery could change the face of energy as we know it, but is it patentable?

*The information about the experiment and its results is from Science Daily. Please read their article for more details, it’s a great read:

Wyss Institute for Biologically Inspired Engineering at Harvard. “Electrical generator uses bacterial spores to harness power of evaporating water.” ScienceDaily. ScienceDaily, 27 January 2014. <www.sciencedaily.com/releases/2014/01/140127101242.htm>.

Patenting Lactobacillus?

If the scientists who genetically modified the lactobacillus bacterium asked me if I thought they could patent the bacterium I  would say (after telling them that I am just a law student), “I think you have a really good chance based on the criteria set out in Diamond v. Chakrabarty.” Remember in that case, the scientist was able to patent a bacterium from the Psuedomonas genus. The court found that because the bacterium was genetically modified and was different from any other bacterium found in nature, it was the scientist’s own handiwork, and not nature’s.

In the same vein, the scientists who have genetically modified lactobacillus to recognize and bind to HIV are creating a phenomena that does not occur in nature. In addition, the genetic modification makes a significant change to the bacterial species. Meaning, if you take the genome of the lactobacilli that occur freely in nature, and you take the modified lactobacillus genome, the two would be different in a significant way. The other two factors are straightforward: yes, the bacterium has been put to a different use (preventing HIV infection) and yes the bacterium’s range of utility has been enlarged. The utility is enlarged because instead of just performing its typical function, producing lactic acid in  the vaginal tract and thus decreasing the pH, the bacterium will help fight HIV. Although, a lower pH is helpful to keep bacteria that would be harmful in a more alkalinic environment at bay, quenching HIV and preventing it from binding to T-helper cells is much different.

Lastly, whether the bacterium is a “new” microbe would be question that could only be answered with more scientific research, and of course the Court’s blessing. The term “new” is more ambiguous but it is a topic that is ripe for litigation. (I would be more than happy to argue in front of the Court that the bacterium is “new” in this case…in about two more years). So…yes…feel free to contact me scientists! :).

Happy Saturday!

-S

Summary of analysis using Diamond:

◾Has the bacterium/microbe obtained a different use? Most likely yes.
◾Is it a new bacterium/microbe? Maybe.
◾Has any change to the bacterial/ microbial species been made? Most likely yes.
◾Has the bacterium’s range of utility been enlarged? Most likely yes.

Up to date summary of the experiment:

http://www.ncbi.nlm.nih.gov/pubmed/23318049

Lactobacillus: The Soldier of the Vaginal Tract

The Human Immunodeficiency Virus (“HIV”) is one of the most commonly known microbes in American history. HIV is also one of the most devastating because it diminishes the immune system, leaving the victims susceptible to diseases that others who are immuno-competent would not be susceptible to. Some how, the virus has evolved to infect the very cells that are responsible for “killing” the virus.

Simplified Background on HIV infection:

Essentially, HIV infects the T-helper cells of the immune system. T-helper cells help elicit an immune response against foreign invaders with the help of antibodies. Antibodies are basically proteins that recognize the foreign invader, bind to it, and mark it for destruction. Most antibodies can only bind to foreign invaders they have previously been exposed to. The T-helper cell is distinguished from its cousin, Cytotoxic T cells by the CD4+ receptor found on the T-helper’s cell surface.

HIV enters T-helper cells by binding to the CD4+ receptor. After HIV binds to the CD4+ receptor, a co-receptor is revealed which facilitates its further entrance into the cell. Once inside the cell HIV may remain latent for years, or become active and acutely cause the manifestations of the disease, “AIDS” (Acquired Immune Deficiency Syndrome). 

Lactobacillus and the “Cure”: 

Although it very difficult to find a cure for HIV because the virus constantly evolves, creating a quasi species that antibodies cannot recognize, advancements in HIV research are being made everyday. One of the most interesting articles that I’ve come across in Nature discussed the use of the bacterium, lactobacillus, found in the female vaginal tract. According to the article, “Prevention of vaginal SHIV transmission in macaques by a live recombinant Lactobacillus” by Lagenaur et. al., lactobacilli are being used to prevent HIV infiltration and subsequent infection.

Basically, scientists are genetically altering the lactobacilli to recognize HIV, bind it and quench the virus (like an antibody). The idea is, if HIV is bound to lactobacilli, it can’t bind to the CD4+ receptor on the surface of the T-helper cells. According to the article, the experiment was conducted in monkeys (like the polio vaccine) using Simian HIV (SHIV). The experiment showed that the re-engineered lactobacilli reduced SHIV infection by sixty-three percent. If the lactobacilli become just as effective in human females then the implications are of course astronomical! Maybe we can stop HIV with a simple bacterium already found in the female vaginal microflora. Certainly, as mentioned by the article, this method is far less expensive than manufacturing a drug.

The question is whether the genetically modified lactobacilli would be patentable if it was also effective in humans?

There was a really good seminar that may answer this, posted by PatentBaristas:
http://www.patentbaristas.com/archives/2013/09/12/section-101-patent-eligibility-issues-in-the-life-sciences/

The Science Article:
http://www.nature.com/mi/journal/v4/n6/full/mi201130a.html#aff1

“Monopoly” is not just a board game

So why do we CARE about patents anyway? What’s the big deal? Let’s say, for argument’s sake, that no one wants to “steal” my idea and use it for his or her own purposes. What would I gain from patenting my invention?

Well, according to “Inventions Patentable” statute, a patent comes with a right. The patent and the right to patent are both personal property that are related to the idea of “bundle of sticks.” “Ownership” in property is not just one thing, it is made up of multiple parts. One part being, the fundamental right to exclude others from the use or enjoyment of that property (at least that’s what my Property professor taught me).

So, even if no one wants to “steal” your idea, without a patent you can’t exclude others from making, using or selling your invention.Yes patents are that important! The key thing is that if your invention is patentable, the government will give you a monopoly over the patent for a certain amount of time, in exchange for disclosure of your invention to the public, quid pro quo. 35 U.S.C., 1946 ed., § 101.

However, a patent is so much more than a “contract” between the inventor and the government. A patent is a privilege granted by Article I, section 8, clause 8 of the United States Constitution used to promote useful inventions in arts and science. Id. A patent rewards an inventor, and this reward is protected by our own U.S. Constitution. However, after reading the “Construction of patent rights” provision of the statute, I found that there is a tension. The tension is between rewarding the inventor with monopoly in exchange for disclosure of the invention to promote the public good and rewarding the inventor so much that it unconstitutionally discourages competition from other inventors.  

If an inventor’s patent protection is so high that it discourages competition, then this would be contrary to public interest because the progression of art and science through competition would be blocked and that is unconstitutional. Id.

So what does all of this mean in the context of science, of microbiology? Well, it explains why you can’t patent the mold you find on your cheese in the refrigerator. If I grant you a patent for that moldy cheese, you would have the right to exclude me from the moldy cheese in my refrigerator. I could not use the moldy cheese without your permission. In the same vein, it explains Jonas Salk’s famous quote “[w]ould you patent the Sun?” Of course the answer is no. A person cannot receive a patent for the Sun and exclude you from bathing in it, no more than they can exclude you from using the moldy cheese in your refrigerator.

Now that is food for thought, over and out.

-S