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>.

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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

Salk’s Vaccine

Poliomyelitis devastated the world. Even more so in less developed countries that lacked the capacity for proper sanitation. Essentially, an individual would ingest the virus if he or she consumed contaminated food and drink through the “fecal-oral” route. The infection would eventually lead to permanent paralysis. Children were one of the most susceptible groups of people.

Jonas Salk and Albert Sabin developed two distinct vaccines to cure polio. Salk’s vaccine was the “dead” virus, while Sabin’s vaccine was the attenuated or weakened virus. The difference is the latter was replicated and evolved in different host organisms. Sabin’s vaccine elicited a complete immune response to the virus. Salk’s vaccine was “killed” by high salt concentration, and was not therefore a complete virus, only components of the virus which did elicit an immune response, but not one that was as strong as Sabin’s vaccine.

The issue was, an attenuated virus could, although the chances were slim, revert to its previous infectious state. The public was concerned with the Sabin vaccine reverting and actually causing a polio infection. So, the Salk vaccine became the “go-to” vaccine because a “dead” virus could not revert because the virus was not whole.

There was no doubt that Salk’s vaccine was not only innovative, but useful. So why did Salk decide not to patent his vaccine? After all the Congressional intent of the “Inventions Patentable” statute is to promote newly discovered technologies…including microorganisms. 35 USC § 101. Does his virus/microbe weigh in favor of the following factors?

  • Has the bacterium/microbe obtained a different use?
  • Is it a new bacterium/microbe?
  • Has any change to the bacterial/ microbial species been made?
  • Has the bacterium’s range of utility been enlarged?

“Would you patent the Sun?” -Jonas Salk

The statute, “Inventions Patentable,” 35 USC § 101 states that the intent of Congress in enacting the statute is to “promote useful arts by securing for limited times to inventors exclusive right to their discovery.” Furthermore, the Supreme Court stated that the purpose of patent law is to reward individual achievement. 35 U.S.C. § 101, “Purpose.”

The question is whether drawing the line between raw nature, and modified nature promotes the purpose of patent law. The short and sweet answer is yes. It makes perfect sense to only reward inventions that are separate and distinct from what nature itself has created. No one can be credited for what nature creates. He must use what is derived from nature to come upon a new use of such, applying the four-factor test described in Diamond.

Jonas Salk creator of one of the polio vaccines (there were two different kinds) asked “[w]ould you patent the sun?” What does that mean? How does that relate to his own invention? How does that relate to patenting bacteria?

Yes, he discovered the law of gravity. So what?

If you discover one of the greatest mysteries of all time you will climb to fame. Every one will know your name. You will be in history books. All the greatest kings of the world will kneel at your feet. However, can you patent your discovery? Not necessarily. Just ask Einstein who discovered the law of gravity, a concept that has been theorized since the 1600’s. Gravity is a manifestation of nature and those, according to the Supreme Court and 35 USC § 101 are off limits! Not patentable. However, as my father would say, “you cannot know the law without knowing its exceptions,” and indeed there is an exception.

In 1980, the Supreme Court decided the case, Diamond v. Chakrabarty.  In the case, a microbiologist created a man-made genetically engineered bacterium that had the capability to break down several different components of crude oil. Diamond v. Chakrabarty, 447 U.S. 303, 305 (1980). This bacterium was from the genus Pseudomonas. Id. Now bacteria from the Pseudomonas genus are gram negative bacteria. Some may horribly infect patients in the hospital,  especially if those patients also happen to be burn victims. However, our scientist used the bacterium’s “powers” for good and manipulated the bacterium’s genome by inserting plasmids. Id. (We will talk about plasmids later). Because of this, the bacterium was able to break down the crude oil, and this property was not found in any other bacterium in nature. Id. Although the Office Board of Appeals concluded that § 101 of the statute was not intended to cover living things, even those created in a laboratory, the Supreme Court of the United States reversed this decision stating that the scientist’s microorganism “plainly qualifies as patentable subject matter.” Id. at 310.

The Court compared the scientist in this case with the scientist in Funk. Id. In Funk, the scientist did not create 1) a species of bacteria that has obtained a different use, 2) the combination of the species that produced new bacteria, 3) a change in any of the bacterial species and 4) “an enlargement in the range of the bacteria’s utility.” Id. As a result, the scientist in Funk did not alter the nature of the bacteria, the bacteria “perform[ed] in their natural way.” Id.  Contrarily, the scientist in this case made a new bacterium, that was useful, and not like any other bacterium found in nature. Id. Therefore, the court reasoned that his discovery was “not nature’s handiwork, but his own; accordingly it is patentable. . . .” Id.

So, the exception falls under a sort of “four-factor” test, established in Funk and applied in Diamond.

  1. Has the bacterium/microbe obtained a different use?
  2. Is it a new bacterium/microbe?
  3. Has any change to the bacterial species been made?
  4. Has the bacterium’s range of utility been enlarged?

Think about it, you don’t have to be Einstein. Over and out!

-S

Three Types of Patents

There are three types of patents: Utility patents, Design patents, and Plant patents. (http://www.uspto.gov/patents/).

Utility patents are granted to those who have invented or discovered a “process, machine, *article of manufacture, or composition of matter” that is NEW and USEFUL.

Design patents must also be new but “original” with respect to designing “an *article of manufacture.”

Plant patents are granted when a distinct and new type of plant is invented/discovered and asexually reproduced.

Essentially there are four categories of discoveries or inventions that are patentable as a “utility” patent:

1) process

2) article of manufacture

3) machine

4) composition of matter

The U.S. Court of Appeals defines an *article of manufacture as “the production of articles for use from raw or prepared materials by giving to these materials new forms, qualities, properties, or combinations, whether by hand-labor or by machinery.” http://en.wikipedia.org/wiki/Article_of_manufacture

A more in depth analysis applying these categorical terms to discoveries in microbiology will come later in the discussion.