Category: Artificial Molecular Machines

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In May 2009, the American Civil Liberties Union and the Association for Molecular Pathology filed suit, in the United States District Court for the Southern District of New York, against the United States Patent and Trademark Office and Myriad Genetics. The complaint pertained to patents that were granted on the BRCA1 and BRCA2 human genes that are mutations correlated to the increased risk of breast or ovarian cancer.  Myriad Genetics designed a procedure to test for these mutations to indicate the likelihood of a woman developing either or both of the diseases.  The complaint asserted that patents on genes should not be allowed because they are violative of § 101, patentable subject matter, of the Patent Act, namely all three of the judicially recognized exceptions to patentability:  natural phenomena, laws of nature, and abstract ideas. Subsequently, the American Civil Liberties Union and the Public Patent Foundation filed a motion for summary judgment, in August 2009.  On March 29, 2010, the District Court found that the isolated segments of DNA utilized for the diagnostic tests were “not markedly different from native DNA as it exists in nature” and held the patents granted to Myriad were not valid.  Ass’n. for Molecular Pathology v. U.S.P.T.O., 702 F. Supp. 2d 181 (S.D.N.Y. 2010).


On July 29, 2011, the United States Court of Appeals for the Federal Circuit reversed the decision of the district court stating “the molecules as claimed do not exist in nature.”  According to a report on msnbc.com, Bruce Wexler, a partner in the law firm Paul Hastings, commented “[t]he appeals court has now held that isolated DNA is patent eligible, and it recognized that isolated DNA has a different molecular structure than DNA as it exists in the body. That is a very significant result that is very important to the biotech industry.”

    
This decision is equally important to the future of the nanotech industry because the starting point for nearly all nanoparticle inventions is the same as biotech – nature.  While it is well established that those materials found in nature are not patentable, the Federal Circuit has signaled its acknowledgement of the intellectual investment inherent in the advancement of science.  There would have been seismic effects on the future of biotech and nanotech development had the district court’s decision been affirmed.  For now, it is full steam ahead for the scientists and investors.   

For further information, see an earlier post I wrote - Patents on Genes and the Future of Personal Nanomedicine.

Read the full Federal Circuit decision here: http://www.aclu.org/files/assets/10-1406.pdf

www.h20technologies.com

www.h20technologies.com

The U.S. National Nanotechnology Initiative (NNI) Strategic Plan Draft was posted at http://strategy.nano.gov for public comment on November 1, 2010.  The NNI was launched in 2001 with 8 agencies and now consists of the nanotechnology-related activities of 25 agencies.  Fifteen of these agencies have R&D budgets related to nanotechnology.

In reflecting on the 10-year history of U.S. nanotechnology research and development, the NNI Draft highlights its work as having “established a thriving nanotechnology R&D environment, laid the crucial groundwork for developing commercial applications and scaling up production, and created demand for many new nanotechnology and manufacturing jobs in the near-term.”  (Draft, p. 1)  Looking to the future, the NNI notes that nanotechnology R&D is “far from full realization.”  (Draft, p. 2)  The goals of the NNI continue to be broad:  continued development of R&D; developing the technologies into products for commercial and consumer use; and developing the physical and human resources to achieve these goals.

Goal 4 of the Draft Strategic Plan is “Support responsible development of nanotechnology,” including the twin goals of understanding and managing the risks of the technologies.  Among the NNI participating agencies in 2010 are EPA, FDA, National Institutes of Health (NIH), and National Institute for Occupational Safety and Health (NIOSH).

The NNI Draft Strategic Plan focuses directly on the benefits of nanotechnology, rather than the risks.  But many of the participating agencies – and many more – need to be involved on the risk side of the proverbial risk-benefit analysis.  This is happening, as reported previously in posts on this blog ranging from FIFRA to TSCA to the FDCA.

 But equally important is the need for communication and coordination on both the benefits and risks of nanotechnology.  And that extends beyond governmental regulation to businesses and nongovernmental organizations (NGOs).

Aside from governmental action, various voluntary initiatives and partnerships have emerged.  A report out of the Woodrow Wilson  International Center for Scholars, “Voluntary Initiatives, Regulation, and Nanotechnology Oversight:  Charting a Path,” gives an overview of the initiatives – some publicly sponsored, some developed by business, and some representing joint business-NGO partnerships.  These initiatives have the common, though separate, goal of developing a strategy to oversee environmental, health, and safety risks raised by nanomaterials.  The report is available at http://www.nanotechproject.org/publications/archive/voluntary/

Three initiatives discussed in some detail in the report are:

 ●  “Nano Risk Framework,” jointly developed by duPont and the Environmental Defense Fund (EDF)

 ●  “Responsible Nano Code,” sponsored by stakeholders from the United Kingdom

 ●  “Nanoscale Materials Stewardship Program,” developed by EPA

 The report critically analyzes these specific initiatives – as well as others more generally – and concludes that they have a welcome role in the future of nanotechnology safety and health efforts.

The ideal world does not exist, of course.  But in this world, a strategy that incorporates the risks and benefits of these developing technologies and brings together as many varied interests as possible representing all affected parties, including the environment, is warranted.  It can provide needed checks and balances along the way.

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I recently came across a very interesting article that was written in the Summer of 2008, Nanoparticle-based Therapies in Humans: A Survey, available at http://www.rpitechnology.com/files/NANOPA4.pdf. The subject matter deals with medical therapies for humans that contain nanoparticles. The author explores the emerging area of medicine that incorporates nanotechnology to fill the gaps of traditional delivery systems (i.e. poor water solubility and lack of target specificity). In addition to gap filling, the therapies stand poised to take the medical field to a whole new level, and will pose a myriad of challenges for the FDA, the U.S. Patent and Trademark Office (PTO), and patent attorneys worldwide.

Some Broad Background:

It is important to understand why nanoparticles are responsible for the proliferation of a new way to deliver medicine to the ailing human body. Traditional delivery systems lack the specificity element and the medicine tends to be delivered in higher than necessary doses that could lead to possible toxic exposure to the patient. Also, the human body is a hostile environment which reduces the effectiveness of traditional drugs.

The author of the article pointed out the following benefits with regard to the developments in nanomedicine:

Nanoparticles are selected for properties such as biodegradability, biocompatibility, conjugation, complexation or encapsulation and their ability to be functionalized. There are two types of nanoparticle-based therapeutic formulation: (1) those where the therapeutic molecules are the nanoparticles (therapeutic functions as its own carrier); and (2) those where the therapeutic molecules are directly coupled (functionalized, entrapped or coated) to a carrier.

Another important and desirable property of nanoparticles is the “surface area effect” that occurs. As a particle’s size decreases, the number of atoms on its surface increases relative to those at the core. This results in an exponential increase in reactivity which equates to increased efficiency and effectiveness over larger molecule delivery systems.

Patents and Commercialization:

It is critical for a company to obtain valid patents if they have any hope to profit from the research and development efforts of producing a new drug delivery system. According to the author of the article I read, the current state of nanoparticle patents is confusing at best. He states, “the proliferation of nanoparticle patent applications filed at the PTO, coupled with the continued issuance of surprisingly broad patents by the PTO, is creating a chaotic, tangled patent landscape where competing players are unsure as to the validity and enforceability of numerous issued patents.”

In an earlier post, Nanobots, Patents, and Collaboration, I proposed that innovation through collaboration is likely the most ideal way to navigate in this emerging area of technology. It seems as though there is no clear guidance in light of the Bilski decision, other than the probability is high that broad patents will continue to issue (not a bad thing, but not helpful to those involved in developing the multilayered drug delivery systems). I find myself a bit conflicted because I am a proponent of patent protection, but I am a realist and understand that the smaller the technology goes, the more overlap that occurs between competing patents. Again, I assert that collaboration is key and I look forward to participating in the process.

nanotechnology-on-health-area-photoThe University of Buffalo recently unveiled a dramatic development in the nanotech realm. Through the use of magnetic nanoparticles it is possible for scientists to “remotely control ion channels, neurons and even animal behavior.” There are many possible real-world applications of this technology including targeted cancer, diabetes, and neurological disorder treatments.

The method utilized in the control of animal behavior involves the use of magnetic nanoparticles which have entered into the cell membrane of the nematode C. Elegans. The size of the particles, only six nanometers, is essential for the easy movement into the cell membrane. Once situated, the subject was exposed to a magnetic field (much like the intensity of an MRI) and the nanoparticles were heated to 34 degrees Celcius (93.2 degrees Fahrenheit). The worms, which had been moving in a forward direction, move in the opposite direction when the temperature rose.


Group of C. Elegans worms prepared by UB team with nanoparticles at their sensory neurons respond to the application of a magnetic field. To learn more, visit http://www.buffalo.edu/news/11518

“We targeted the [magnetic] nanoparticles near what is the ‘mouth’ of the worms, called the amphid,” explained Arnd Pralle, PhD, assistant professor of physics. “You can see in the video that the worms are crawling around; once we turn on the magnetic field, … most of the worms reverse course. We could use this method to make them go back and forth. Now we need to find out which other behaviors can be controlled this way.”

The implications of this breakthrough could just as easily be applied to humans. Already, there are groups utilizing magnetic nanoparticles to battle cancer cells in a very targeted manner. But, the net is cast wider with the application to remotely controlling animal and human behavior.

In the legal arena, one could pose the question “Is this discovery worthy of patent protection?” Post Bilski, 2010 WL 2555192, the question might easily be answered with regard to patentable subject matter and processes. Now that the machine or transformation test is not exclusively definitive, it is more likely than not the process of heating magnetic nanoparticles to cause a living organism to behave differently would clear the first hurdle on the path to a patent. Of course, the battle would continue in the ‘non-obvious’ and ‘prior publication’ stages, however, innovation is not stifled and the legal battles rage on.

supct

The paradigm to determine the patentability of inventions involving nanotechnology and biotechnology continues to evolve due to the Supreme Court deciding the case of Bilski v. Kappos, 2010 WL 2555192.  The Court heard oral arguments on November 9, 2009, and the opinion was issued on Monday, 28 June 2010.

The trouble for Bilski began when he and his business partner, Warsaw, applied for a patent on a computerized method for incorporating weather information into the speculation of future prices of commodities and energy costs (business method). The claim was denied by the Patent and Trademark Office (PTO) for lack of patentable subject matter (process), and the denial was affirmed in subsequent appeals to the PTO and the Federal Circuit. The Supreme Court decision affirmed the denial of the business method’s patentability, but it simultaneously held the test, utilized by the Federal Circuit, for determining if a process is proper patentable subject matter was not the exclusive and sole determining factor. Going forward, this decision will have a major impact on what constitutes patentable subject matter (the first hurdle on the road to a patent being issued), including those discoveries that have helped to fuel the explosion of cutting-edge bio/nanotechnology.

BACKGROUND OVERVIEW

Throughout the litigation history, the focus was squarely on the ‘machine or transformation’ requirements articulated by the PTO and further solidified by the Federal Circuit.  The court relied on the two prong test set forth in Gottschalk v. Benson to determine whether a process claim is tailored narrowly enough. “A claimed process is surely patent-eligible under § 101 if:  (1) it is tied to a particular machine or apparatus, or (2) it transforms a particular article into a different state or thing.” The Federal Circuit outlined the task at hand, “It is undisputed that [Bilski’s] claims are not directed to a machine, manufacture, or composition of matter. . . . Thus, the issue before us involves what the term ‘process’ in [the law] means, and how to determine whether a given claim . . . is a ‘new and useful process.’”  Essentially, the legal issue generating all the consternation and strife is: “[W]hat test or set of criteria governs the determination by [PTO] or courts as to whether a process is patentable?”  The Federal Circuit opined that a process is not patentable subject matter unless it exactly conforms with the ‘machine or transformation’ test.

THE SUPREME COURT

The Supreme Court agreed to hear the case, but rarely hears a case from the Federal Circuit to explain that they reached the correct and appropriate conclusion. Quite to the contrary, the Supreme Court seems to take case after case in the patent area to fix a wrong perpetrated by the Federal Circuit. This tension has been in place for quite some time.

At oral arguments before the Supreme Court, Justice Sotomayor voiced concern over the harsh majority opinion of the Federal Circuit:

How about we say something as simple as patent law does not protect business matters instead of what the Federal Circuit has begun to say, which is technology is tied to a machine or a transformation of the substance, but I have no idea what the limits of that ruling will impose in the computer world, in the biomedical world, all of the amici who are talking about how it will destroy industries?

That sentiment reverberated in the unanimous majority opinion whereby the ‘machine or transformation’ test was relegated to the role of a helpful clue in determining whether or not a process is patentable subject matter. Essentially, the Court rejected the Federal Circuit’s exclusive reliance on the bright-line rule and threw the proverbial ball back into their court to develop an appropriate test. The bottom line, as it stands now, is that patentable subject matter is still quite broad, and the analysis to determine it includes the ‘machine or transformation’ test as one criterion with regard to processes, but it no longer is the sole deciding factor.

ONWARD

If the Supreme Court had required strict adherence to the machine or transformation test, it would have had seismic implications for patents already issued, and certainly would have caused trouble for pending applications relating to biotechnology and nanotechnology.  The trouble arises from the precarious position that biotech and nanotech patents are not theoretically involved with either a machine nor do they transform matter.  Generally speaking, they are processes involved with analysis, diagnosis, treatment or some type of function. Notable examples are those nanoparticles involved in drug delivery. Even though the particles behave differently at the nanoscale level, they essentially are not transformed or part of a machine and would thus fall outside patent protection under the rigid Federal Circuit test. Now, there is a least the possibility for these types of inventions to move forward in the process of patentability.

Ultimately, the parties in Bilski did not receive the patent on the specific business method that was applied for; however, the patent world at large was able to avoid the strictures of the rigid, bright-line ‘machine or transformation’ test utilized by the Federal Circuit .  In essence, the fields of nanotechnology and biotechnology research and development dodged a catastrophic bullet. In the coming weeks and months I plan to return to this discussion in relation to emerging technology, especially after the PTO, practitioners, judges, and legislators have had time to digest the nuances of this landmark decision.

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It is clear that the time has come to integrate cutting-edge science and the law.  In addition to the policy issues involving individuals, it is important to our nation because we must continue our leading role as the innovators of the world.  Furthermore, there is a tremendous amount of money at stake for our economy.  Historically, the method by which to protect the vast amount of money that is invested and earned from scientific research is patent protection.  That must continue.  However, a possible starting point for compromise is collaboration between scientists who invent a new and useful product, derived from biological material, and those who wish to utilize the technology to further the development of particular areas of science leading to additional inventions.

A prime example of a partnering between two groups of scientists in the realm of nanotechnology and biotechnology is that of the DNA robot.  Researchers from Columbia University, Arizona State University, and Caltech have created a Nanobot that follows a programmable path on a surface patterned with DNA (more commonly referred to as DNA origami). Simultaneously, researchers from New York University, led by Ned Seeman, have combined multiple DNA devices to make an assembly line. The DNA robot picks up gold nanoparticles while navigating along a DNA-labeled surface.  The details were released in the May 13th edition of Nature:  http://www.nature.com/nature/journal/v465/n7295/pdf/nature09012.pdf.

Essentially, scientists are at the beginning stages of creating test-tube factories that have the potential to create self-assembling computers, rare chemical compounds or autonomous medical robots able to embark on specialized missions in the human bloodstream. “[We're] moving from individual entities that do something interesting to systems of entities working on something with a more complex behavior and function,” says Lloyd Smith, a chemistry professor at the University of Wisconsin-Madison.

The California Institute of Technology has applied for a patent on DNA origami, invented by Professor Rothemund.  NYU owns a patent on nano-robotics as a result of the pioneering research conducted by Professor Seeman.  The collaborative effort of these two groups reflects the benefits that are possible through non-enforcement of patents in the early stages of scientific development.  Furthermore, as a result of the partnering, it would be unnecessary for the government to get involved in the regulation of innovation.  A natural outflow of a collective approach would be the development of self-regulating industry standards to shape and guide the evolution of  the interaction between science and the law.

www.inoxpa.com

www.inoxpa.com

According to a recent report from the United States Government Accountability Office (GAO), the FDA is currently taking a hands-off approach to food additives that contain engineered nanoparticles.  In fact, the FDA does not require food manufacturers to report additives that are deemed generally regarded as safe (GRAS).  Who determines the GRAS status?  The food manufacturers, without oversight or approval from the FDA!  The following excerpt from the GAO report, United States Government Accountability Office, Report to Congressional Requesters, Food Safety: FDA Should Strengthen Its Oversight of Food Ingredients Determined to be Generally Recognized as Safe (GRAS) (2010), provides a realistic and chilling view at the current intersection of the American food supply and nanotechnology:

FDA’s approach to regulating nanotechnology allows engineered nanomaterials to enter the food supply as GRAS substances without FDA’s knowledge. While some uses of engineered nanomaterials have the potential to help ensure food safety, uncertainties remain about how to determine their safety in food. After reviewing the uncertainties associated with the safety of engineered nanomaterials, FDA has decided that it does not need additional authority to regulate products containing such materials. Rather, FDA encourages, but does not require, companies considering using engineered nanomaterials in food to consult with the agency regarding whether such substances might be GRAS. Because GRAS notification is voluntary and companies are not required to identify nanomaterials in their GRAS substances, FDA has no way of knowing the full extent to which engineered nanomaterials have entered the U.S. food supply as part of GRAS substances. In contrast to FDA’s approach, all food ingredients that incorporate engineered nanomaterials must be submitted to regulators in Canada and the European Union before they can be marketed.

Id. at Highlights page (emphasis added).

The application of nanotechnology to food is potentially very beneficial. Two specific examples are 1) nanotags to “improve the traceability of food products (the ability to track these products from point of origin to retail sale)” and 2) the most prolific “usage appears to be in food packaging, where applications such as antimicrobial nanofilms—thin layers of substances meant to hamper the growth of bacteria and fungi—may help bolster food safety.” Notwithstanding the current and obvious benefits, the FDA, and its foreign counterparts, realized that the potential for hidden challenges does exist.  As a result, the FDA created a taskforce in 2007 to identify some of the potential pitfalls, and to recommend possible solutions. The taskforce identified several challenges posed by utilizing nanotechnology, specifically “ensuring the adequacy of methods for evaluating the safety of these engineered nanomaterials in food.” It also made mention of how little the FDA actually knows about nanotechnology and as a result, declined to include a definition of it in its report. (GAO Report 26-27).

At this point in time, even if something were to go awry as a result of nanomaterials being utilized in the food supply, where does the blame fall? According to current administrative law, the courts take an extremely deferential stance in favor of agency decisions when it comes to science. In Baltimore Gas & Elec. Co. v. Natural Res. Def. Counsel, 462 U.S. 87, 103 (1983), the Court stated, “[a] reviewing court must remember that the [agency] is making predictions, within its area of special expertise, at the frontiers of science. When examining this kind of scientific determination, . . . , a reviewing court must generally be at its most deferential.” This case dealt with a rule adopted by the Nuclear Regulatory Commission (NRC) based on findings “that permanent storage of nuclear waste would have no significant environmental impact.” Michael Asimov & Ronald M. Levin, State and Federal Administrative Law 595 (3d ed. 2009). This leads one to believe that if the NRC received this level of deference in the early stages of nuclear energy proliferation, the courts would almost certainly provide the same to the FDA’s lackadaisical decision-making approach to nanotech and the food we eat.

I certainly do not wish to suggest that the use of nanomaterials in our food supply is going to lead us down the long road of massive tort litigation, but I do wish to assert that if we are not vigilant from the very beginning, it is anyone’s guess where it could lead.

www.gao.gov/new.items/d10246.pdf

www.foodsafetynews.com/2010/03/gao-fda-does-not-ensure-safety-of-food-additives/